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CompletedNCT04200911CARPE_DIEMUpdated Jan 8, 2025Results posted

Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway

An Early Phase 1 interventional study of Rapamune in Cognitive Impairment, Mild and Alzheimer Disease, sponsored by The University of Texas Health Science Center at San Antonio. Completed at 1 site in United States. Open to participants aged 55 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-01-08.

Sponsored by The University of Texas Health Science Center at San Antonio · Early Phase 1, Interventional, and Treatment

Phase
Early Phase 1
Study type
Interventional
Enrollment
10
Allocation
Not applicable
Ages
55 Years to 85 Years
Sex
All
01

Study summary

Evaluation of central nervous system penetration of orally administered Rapamune (RAPA) in older adults with Mild Cognitive Impairment (MCI) or early Alzheimer's disease (AD) and investigate associated safety, tolerability, target engagement, cognition, and functional status as initial proof-of-concept study

Read the detailed description

This study is an open-label pilot study of orally administered RAPA to measure its target engagement in Cerebrospinal Fluid (CSF) and blood, and to establish the feasibility and safety of RAPA treatment in older adults with MCI and early stage AD as initial proof-of-concept for a larger Phase 2 clinical trial.

02

Conditions studied

  • Cognitive Impairment, Mild
  • Alzheimer Disease
03

In context

Cognitive Dysfunction

3,930 studies on the registry are indexed under Cognitive Dysfunction; 1,114 are open to participants now.

This study's enrollment of 10 is below the median of 64 across 2,855 interventional studies indexed under Cognitive Dysfunction.

Browse Cognitive Dysfunction studies →

Lead sponsor

The University of Texas Health Science Center at San Antonio is the lead sponsor of 443 studies on the registry; 88 are open to participants now.

Of its 64 completed or terminated interventional studies of FDA-regulated products, 35 (55%) have results posted.

Browse The University of Texas Health Science Center at San Antonio studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
55 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Diagnosis of Mild Cognitive Impairment (MCI) or Alzheimer's disease, Global Clinical Dementia Rating Scale (CDR)=0.5-1
  • Normal blood cell counts without clinically significant excursions; ; normal liver and renal function; and glucose control (HbA1c \< 6.5%). Lipid panel and PT/PTT/INR within normal limits
  • A Legally Authorized Representative (LAR) if necessary for consent
  • An LAR or study partner to accompany participant to all visits
  • Availability for all study visits
  • Stable dose of AD medications) Donepezil, rivastigmine, memantine, galantamine) for at least 3 months prior to the baseline visit

Exclusion criteria

Exclusion Criteria:

  • Diabetes (HbA1c≥6.5% or anti-diabetic medications)
  • History of skin ulcers or poor wound healing
  • Current tobacco or illicit drug use or alcohol abuse
  • Use of anti-platelet or anti-coagulant medications other than aspirin
  • Current medications that affect cytochrome P450 3A4; current or recent medications for hypertriglyceridemia (eg, Gemfibrozil)
  • Hypersensitivity or history of allergy to Rapamycin
  • Immunosuppressant therapy within the last year; current treatment with hydroxychloroquine and chloroquine (requires "washout period" of 14 days)
  • Chemotherapy or radiation treatment within the last year
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities
  • History of primary hypertriglyceridemia. Abnormal triglycerides >200 or LDL cholesterol >193, or other abnormal labs deemed clinically significant upon investigator review
  • Current or chronic history of pulmonary disease or abnormal pulse oximetry (\<90%)
  • Chronic heart failure
  • Pregnancy
  • Recent history (past 6 months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack
  • significant neurological conditions other than AD
  • Poorly controlled blood pressure (systolic BP>160, diastolic BP>90mmHg)
  • Active inflammatory, COVID-19, autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or psychiatric disease
  • History of, or Magnetic Resonance Imaging (MRI) positive for any space occupying lesion, including mass effect and/or abnormal intracranial pressure, which would indicate contraindication to lumbar puncture
  • Organ transplant recipients
05

Study design

Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
10 participants (actual)

Study arms

  • Experimental
    RAPA intervention

    Sirolimus 1mg orally once a day for 8 weeks

    Drug: Rapamune

Interventions

  • DrugRapamune

    Sirolimus 1mg capsules

    Also known as: Sirolimus

06

What researchers measure

Primary outcomes

  1. Blood Brain Barrier Penetration of RAPA

    Lumbar punctures will be performed at baseline and after the final RAPA dose, to assess CSF levels of the drug. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: Change from Baseline to 8 weeks

Secondary outcomes

  1. Adverse Events

    Number of adverse events experienced across all 10 subjects after they were enrolled and randomized to treatment, regardless of relatedness to intervention.

    Time frame: Baseline to 8 weeks

  2. Change in Vitals From Baseline to 8 Weeks

    Evaluation of vitals. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: Baseline to 8 weeks

  3. Percentage of Study Drug Pills Taken

    Average percentage of study drug pills taken across all 10 subjects after they were enrolled and randomized to treatment. The percentage of study drug pills taken was evaluated by having participants return any leftover study drug pills at each visit during the active treatment period.

    Time frame: Baseline to 8 weeks

  4. Change in CSF AD Biomarkers From Baseline to 8 Weeks

    Evaluation of CSF AD biomarkers. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: Baseline to 8 weeks

  5. Change in Plasma AD Biomarkers From Baseline to 8 Weeks

    Evaluation of plasma AD biomarkers. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: Baseline to 8 weeks

  6. Change in CSF Inflammatory Markers From Baseline to 8 Weeks

    Evaluation of CSF inflammatory markers. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: Baseline to 8 weeks

  7. Change in Plasma Inflammatory Markers From Baseline to 8 Weeks

    Evaluation of plasma inflammatory markers. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: Baseline to 8 weeks

  8. Safety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks

    Evaluation of safety labs - white blood cell and platelet counts. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: Baseline to 8 weeks

  9. Safety Labs - Change in Red Blood Cell Count

    Evaluation of safety labs - red blood cell counts. Change in red blood cell count calculated as value at 8 weeks minus the value at baseline.

    Time frame: Baseline to 8 weeks

  10. Safety Labs - Change in Mean Corpuscular Volume

    Evaluation of safety labs - Change in Mean Corpuscular volume. Change is calculated as value at 8 weeks minus the value at baseline

    Time frame: 8 weeks

  11. Safety Labs - Change in Mean Corpuscular Hemoglobin

    safety labs - Mean Corpuscular Hemoglobin. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8-weeks

  12. Safety Labs - Change in Metabolic Parameters (g/dl)

    Evaluation of safety labs - metabolic parameters. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  13. Safety Labs - Change in Hematocrit

    Evaluation of of safety labs - hematocrit. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  14. Safety Labs - Change in Monocytes

    Evaluation of of safety labs - monocytes. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  15. Safety Labs - Change in Red Cell Distribution Width

    Evaluation of of safety labs - Red cell distribution width. Change is calculated as value at 8 weeks minus the value at baseline. The value reported is % of red blood cell size and volume variability.

    Time frame: 8 weeks

  16. Safety Labs - Change in Hemoglobin A1c

    Evaluation of of safety labs - hemoglobin A1c. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  17. Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl)

    Evaluation of safety labs - metabolic and lipid parameters. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  18. Safety Labs - Change in Sodium and Potassium (mmol/L)

    Evaluation of safety labs - sodium and potassium. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  19. Safety Labs - Change in Liver Panel (iU/L)

    Evaluation of safety labs - liver panel. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  20. Cognition/Functional Status - Change in Montreal Cognitive Assessment (MoCA)

    The Montreal Cognitive Assessment (MoCA) assesses global cognition with scores ranging from 0 to 30 points. Higher scores indicate better performance.Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  21. Cognition/Functional Status - Change on the Clinical Rating Scale Global Score

    The Clinical Rating Scale Global Score assesses cognition and daily functioning with scores ranging from 0 to 3 points. Higher scores indicate worse cognition and/or functional status.Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  22. Cognition/Functional Status - Change on the Clinical Rating Scale Sum of Boxes Score

    The Clinical Rating Scale Sum of Boxes assesses cognition and daily functioning with scores ranging from 0 to 18 points. Higher scores indicate worse cognition and/or functional status.Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  23. Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Immediate Recall

    The Hopkins Verbal Learning Test - Revised Immediate Recall assesses verbal list learning with scores ranging from 0 to 36 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  24. Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Delayed Recall

    The Hopkins Verbal Learning Test - Revised Delayed Recall assesses verbal list learning with scores ranging from 0 to 12 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  25. Cognition/Functional Status - Change on the Craft Story Immediate Recall Verbatim

    The Craft Story Immediate Recall Verbatim assesses verbal narrative learning with scores ranging from 0 to 44 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  26. Cognition/Functional Status - Change on the Craft Story Delayed Recall Verbatim

    The Craft Story Delayed Recall Verbatim assesses verbal memory recall with scores ranging from 0 to 44 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  27. Cognition/Functional Status - Change on the Benson Figure Copy

    The Benson Figure Copy assesses visuoconstructional skills with scores ranging from 0 to 17points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  28. Cognition/Functional Status - Change on the Benson Figure Delayed Recall

    The Benson Figure Delayed Recall assesses visual memory with scores ranging from 0 to 17 points. Higher scores indicate better performance.Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  29. Cognition/Functional Status - Change on the Number Span Forward

    The Number Span Forward test assesses basic attention with scores ranging from 0 to 16 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  30. Cognition/Functional Status - Change on the Number Span Backward

    The Number Span Backward test assesses working memory with scores ranging from 0 to 14 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  31. Cognition/Functional Status - Change on the Trail Making Test Part A, Time to Completion

    The Trail Making Test Part A, time to completion assesses psychomotor speed and visual scanning with scores ranging from 1 to 150 seconds. Higher scores indicate worse performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  32. Cognition/Functional Status - Change Trail Making Test Part B, Time to Completion

    The Trail Making Test Part B, time to completion assesses attentional shifting with scores ranging from 1 to 300 seconds. Higher scores indicate worse performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  33. Cognition/Functional Status - Change on Phonemic Fluency

    The Phonemic fluency test assesses speeded word generation to a phonemic cue. Scores begin at 0 with no upper limit. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  34. Cognition/Functional Status - Change on Semantic Fluency

    The Semantic fluency test assesses speeded word generation to a semantic cue. Scores begin at 0 with no upper limit. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  35. Cognition/Functional Status - Change on the Multilingual Naming Test

    The Multilingual Naming Test assesses confrontation naming. Scores range from 0 to 32 and higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  36. Cognition/Functional Status - Change on the Hayling, Total Errors

    The Hayling assesses response inhibition errors. Scores range from 0 to 30 and higher scores indicate worse performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  37. Cognition/Functional Status - Change on Grip Strength, Dominant Hand

    The grip strength, dominant hand assesses grip strength in kilograms. Values begin at 0 with no upper limit. Higher scores indicate better performance Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  38. Cognition/Functional Status - Change on Grip Strength, Non-dominant Hand

    The grip strength, non-dominant hand assesses grip strength in kilograms. Values begin at 0 with no upper limit. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  39. Cognition/Functional Status - Change on the Geriatric Depression Scale 15-item

    The Geriatric Depression Scale 15-item assesses depressive symptomatology. Scores range from 0 to 15 and higher scores indicate worse outcomes. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  40. Cognition/Functional Status - Change on the Functional Activities Questionnaire

    The Functional Activities Questionnaire assesses functional status for independent activities of daily living. Scores range from 0 to 30 and higher scores indicate worse outcomes. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

  41. Cognition/Functional Status - Change on the Neuropsychiatric Inventory Questionnaire

    The Neuropsychiatric Inventory Questionnaire assesses neuropsychiatric symptoms. Scores range from 0 to 12 and higher scores indicate worse outcomes. Change is calculated as value at 8 weeks minus the value at baseline.

    Time frame: 8 weeks

07

Results

Posted Mar 21, 2023

Participant flow

Subjects that were enrolled and passed eligibility screening and went on to randomization.

Participant flow — Overall Study
MilestoneRAPA Intervention
Started10
Completed10
Not completed0

Outcome measures

PrimaryBlood Brain Barrier Penetration of RAPA

Lumbar punctures will be performed at baseline and after the final RAPA dose, to assess CSF levels of the drug. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
Change from Baseline to 8 weeks
Reported as:
Mean · ng/ml
Blood Brain Barrier Penetration of RAPA
ng/mlRAPA Intervention
Blood Brain Barrier Penetration of RAPA0 ± 0
SecondaryAdverse Events

Number of adverse events experienced across all 10 subjects after they were enrolled and randomized to treatment, regardless of relatedness to intervention.

Time frame:
Baseline to 8 weeks
Reported as:
Number · Events
Adverse Events
EventsRAPA Intervention
Adverse Events20
SecondaryChange in Vitals From Baseline to 8 Weeks

Evaluation of vitals. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
Baseline to 8 weeks
Reported as:
Mean · mmHg
Change in Vitals From Baseline to 8 Weeks
mmHgRAPA Intervention
systolic blood pressure10.45 ± 7.82
diastolic blood pressure1.7 ± 5.87
SecondaryPercentage of Study Drug Pills Taken

Average percentage of study drug pills taken across all 10 subjects after they were enrolled and randomized to treatment. The percentage of study drug pills taken was evaluated by having participants return any leftover study drug pills at each visit during the active treatment period.

Time frame:
Baseline to 8 weeks
Reported as:
Mean · percentage of study drug pills taken
Percentage of Study Drug Pills Taken
percentage of study drug pills takenRAPA Intervention
Percentage of Study Drug Pills Taken92 ± 5
SecondaryChange in CSF AD Biomarkers From Baseline to 8 Weeks

Evaluation of CSF AD biomarkers. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
Baseline to 8 weeks
Reported as:
Mean · ng/ml
Change in CSF AD Biomarkers From Baseline to 8 Weeks
ng/mlRAPA Intervention
CSF ptau-1812.64 ± 2.72
CSF abeta 40615.57 ± 1210.06
CSF Abeta4221.52 ± 62.12
CSF GFAP6262.21 ± 4928.96
CSF NFL367.18 ± 310.71
SecondaryChange in Plasma AD Biomarkers From Baseline to 8 Weeks

Evaluation of plasma AD biomarkers. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
Baseline to 8 weeks
Reported as:
Mean · ng/ml
Change in Plasma AD Biomarkers From Baseline to 8 Weeks
ng/mlRAPA Intervention
plasma ptau-181-0.22 ± 0.47
plasma abeta 40-8.86 ± 12.28
Plasma Abeta42-0.67 ± 0.69
Plasma GFAP-27.70 ± 64.78
Plasma NFL0.84 ± 4.64
SecondaryChange in CSF Inflammatory Markers From Baseline to 8 Weeks

Evaluation of CSF inflammatory markers. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
Baseline to 8 weeks
Reported as:
Mean · pg/ml
Change in CSF Inflammatory Markers From Baseline to 8 Weeks
pg/mlRAPA Intervention
IL-100.02 ± 0.02
IL-6-0.02 ± 0.25
IL-85.76 ± 9.10
TNF-α0.03 ± 0.07
IL-120.35 ± 0.53
IL-150.29 ± 0.28
IL-160.63 ± 3.40
IL-17a0.03 ± 0.09
IL-1a-0.15 ± 0.33
IL-50.07 ± 0.07
IL-70.004 ± 0.10
VEGF-A0.95 ± 2.37
VEGF-C266.60 ± 575.93
VEGF-D109.64 ± 117.23
Eotaxin-5.05 ± 32.40
Eotaxin-3-0.20 ± 2.20
IP-10-12.93 ± 143.87
MCP-1-22.56 ± 78.00
MIP1-α0.83 ± 2.90
sFLT-141.18 ± 253.61
PIGF2.84 ± 40.66
bFGF-0.69 ± 20.85
sVCAM121202.57 ± 24439.62
sICAM16701.21 ± 13402.98
SAA-73762.91 ± 375497.74
CRP-98910.45 ± 27540.81
IFN-γ0.14 ± 0.17
SecondaryChange in Plasma Inflammatory Markers From Baseline to 8 Weeks

Evaluation of plasma inflammatory markers. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
Baseline to 8 weeks
Reported as:
Mean · pg/ml
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks
pg/mlRAPA Intervention
IL-10-0.18 ± 0.53
IL-60.29 ± 0.54
IL-80.16 ± 1.57
TNF-α0.06 ± 0.44
IL-12-16.56 ± 38.52
IL-150.12 ± 0.31
IL-1616.18 ± 42.70
IL-17a0.36 ± 1.68
IL-1a-0.20 ± 0.36
IL-50.34 ± 0.46
IL-7-0.14 ± 1.63
VEGF-A-0.05 ± 7.98
VEGF-C2000.38 ± 6648.40
VEGF-D3741.02 ± 3124.38
Eotaxin22.07 ± 36.04
Eotaxin-3-3.60 ± 6.19
IP-1018.26 ± 80.08
MCP-1-4.80 ± 10.74
MIP1-α-0.83 ± 3.64
sFLT-1258.88 ± 237.44
PIGF20.81 ± 11.81
bFGF-143.67 ± 174.71
sVCAM197456.61 ± 1400309.82
sICAM191844.33 ± 1329185.57
SAA190090000 ± 936172849.0
CRP36165816.2 ± 111516450.7
IFN-γ4.37 ± 1.91
SecondarySafety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks

Evaluation of safety labs - white blood cell and platelet counts. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
Baseline to 8 weeks
Reported as:
Mean · x10^3 cells/μL
Safety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks
x10^3 cells/μLRAPA Intervention
White Blood Cell Count0.42 ± 1.92
Immature Granulocytes-0.21 ± 1.19
Eosinophils0.10 ± 2.5
Basophils-0.19 ± 0.40
Platelets20.60 ± 35.19
SecondarySafety Labs - Change in Red Blood Cell Count

Evaluation of safety labs - red blood cell counts. Change in red blood cell count calculated as value at 8 weeks minus the value at baseline.

Time frame:
Baseline to 8 weeks
Reported as:
Mean · x10^6 cells/μL
Safety Labs - Change in Red Blood Cell Count
x10^6 cells/μLRAPA Intervention
Safety Labs - Change in Red Blood Cell Count-0.01 ± 0.27
SecondarySafety Labs - Change in Mean Corpuscular Volume

Evaluation of safety labs - Change in Mean Corpuscular volume. Change is calculated as value at 8 weeks minus the value at baseline

Time frame:
8 weeks
Reported as:
Mean · fL
Safety Labs - Change in Mean Corpuscular Volume
fLRAPA Intervention
Safety Labs - Change in Mean Corpuscular Volume-2.70 ± 2.16
SecondarySafety Labs - Change in Mean Corpuscular Hemoglobin

safety labs - Mean Corpuscular Hemoglobin. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8-weeks
Reported as:
Mean · pg
Safety Labs - Change in Mean Corpuscular Hemoglobin
pgRAPA Intervention
Safety Labs - Change in Mean Corpuscular Hemoglobin-0.81 ± 0.69
SecondarySafety Labs - Change in Metabolic Parameters (g/dl)

Evaluation of safety labs - metabolic parameters. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · g/dl
Safety Labs - Change in Metabolic Parameters (g/dl)
g/dlRAPA Intervention
Hemoglobin-0.27 ± 0.57
Protein-1.77 ± 5.85
Albumin-0.13 ± 0.19
Mean Corpuscular Hemoglobin Concentration0.08 ± 0.85
SecondarySafety Labs - Change in Hematocrit

Evaluation of of safety labs - hematocrit. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · percentage of red blood cells
Safety Labs - Change in Hematocrit
percentage of red blood cellsRAPA Intervention
Safety Labs - Change in Hematocrit-0.86 ± 2.09
SecondarySafety Labs - Change in Monocytes

Evaluation of of safety labs - monocytes. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · percentage of white blood cell count
Safety Labs - Change in Monocytes
percentage of white blood cell countRAPA Intervention
Safety Labs - Change in Monocytes-0.19 ± 4.08
SecondarySafety Labs - Change in Red Cell Distribution Width

Evaluation of of safety labs - Red cell distribution width. Change is calculated as value at 8 weeks minus the value at baseline. The value reported is % of red blood cell size and volume variability.

Time frame:
8 weeks
Reported as:
Mean · Percentage
Safety Labs - Change in Red Cell Distribution Width
PercentageRAPA Intervention
Safety Labs - Change in Red Cell Distribution Width-0.65 ± 0.24
SecondarySafety Labs - Change in Hemoglobin A1c

Evaluation of of safety labs - hemoglobin A1c. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · % of hemoglobin covered w/ glucose
Safety Labs - Change in Hemoglobin A1c
% of hemoglobin covered w/ glucoseRAPA Intervention
Safety Labs - Change in Hemoglobin A1c0.17 ± 0.22
SecondarySafety Labs - Change in Metabolic and Lipid Parameters (mg/dl)

Evaluation of safety labs - metabolic and lipid parameters. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · mg/dl
Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl)
mg/dlRAPA Intervention
glucose2.70 ± 6.67
blood urea nitrogen-1.80 ± 4.13
Creatinine-0.001 ± 0.09
Bilirubin-0.09 ± 0.34
Cholesterol-0.30 ± 26.08
High-Density Lipoprotein Cholesterol2.90 ± 7.22
Low-Density Lipoprotein Cholesterol-2.70 ± 20.38
Very Low-Density Lipoprotein Cholesterol-0.50 ± 4.25
SecondarySafety Labs - Change in Sodium and Potassium (mmol/L)

Evaluation of safety labs - sodium and potassium. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · mmol/L
Safety Labs - Change in Sodium and Potassium (mmol/L)
mmol/LRAPA Intervention
Sodium-5.40 ± 18.90
Potassium-0.19 ± 0.44
SecondarySafety Labs - Change in Liver Panel (iU/L)

Evaluation of safety labs - liver panel. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · IU/L
Safety Labs - Change in Liver Panel (iU/L)
IU/LRAPA Intervention
Aspartate Aminotransferase1.00 ± 4.06
Alanine Transaminase0.001 ± 6.20
Alkaline Phosphatase4.10 ± 10.90
SecondaryCognition/Functional Status - Change in Montreal Cognitive Assessment (MoCA)

The Montreal Cognitive Assessment (MoCA) assesses global cognition with scores ranging from 0 to 30 points. Higher scores indicate better performance.Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change in Montreal Cognitive Assessment (MoCA)
score on a scaleRAPA Intervention
Cognition/Functional Status - Change in Montreal Cognitive Assessment (MoCA)-1.30 ± 2.45
SecondaryCognition/Functional Status - Change on the Clinical Rating Scale Global Score

The Clinical Rating Scale Global Score assesses cognition and daily functioning with scores ranging from 0 to 3 points. Higher scores indicate worse cognition and/or functional status.Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Clinical Rating Scale Global Score
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Clinical Rating Scale Global Score0.15 ± 0.16
SecondaryCognition/Functional Status - Change on the Clinical Rating Scale Sum of Boxes Score

The Clinical Rating Scale Sum of Boxes assesses cognition and daily functioning with scores ranging from 0 to 18 points. Higher scores indicate worse cognition and/or functional status.Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Clinical Rating Scale Sum of Boxes Score
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Clinical Rating Scale Sum of Boxes Score0.55 ± 0.86
SecondaryCognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Immediate Recall

The Hopkins Verbal Learning Test - Revised Immediate Recall assesses verbal list learning with scores ranging from 0 to 36 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Immediate Recall
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Immediate Recall0.40 ± 3.37
SecondaryCognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Delayed Recall

The Hopkins Verbal Learning Test - Revised Delayed Recall assesses verbal list learning with scores ranging from 0 to 12 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Delayed Recall
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Delayed Recall-1.00 ± 2.54
SecondaryCognition/Functional Status - Change on the Craft Story Immediate Recall Verbatim

The Craft Story Immediate Recall Verbatim assesses verbal narrative learning with scores ranging from 0 to 44 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Craft Story Immediate Recall Verbatim
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Craft Story Immediate Recall Verbatim0.20 ± 4.29
SecondaryCognition/Functional Status - Change on the Craft Story Delayed Recall Verbatim

The Craft Story Delayed Recall Verbatim assesses verbal memory recall with scores ranging from 0 to 44 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Craft Story Delayed Recall Verbatim
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Craft Story Delayed Recall Verbatim-1.40 ± 2.95
SecondaryCognition/Functional Status - Change on the Benson Figure Copy

The Benson Figure Copy assesses visuoconstructional skills with scores ranging from 0 to 17points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Benson Figure Copy
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Benson Figure Copy0.70 ± 1.83
SecondaryCognition/Functional Status - Change on the Benson Figure Delayed Recall

The Benson Figure Delayed Recall assesses visual memory with scores ranging from 0 to 17 points. Higher scores indicate better performance.Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Benson Figure Delayed Recall
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Benson Figure Delayed Recall-0.80 ± 2.04
SecondaryCognition/Functional Status - Change on the Number Span Forward

The Number Span Forward test assesses basic attention with scores ranging from 0 to 16 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Number Span Forward
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Number Span Forward0.20 ± 1.62
SecondaryCognition/Functional Status - Change on the Number Span Backward

The Number Span Backward test assesses working memory with scores ranging from 0 to 14 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Number Span Backward
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Number Span Backward-0.60 ± 0.84
SecondaryCognition/Functional Status - Change on the Trail Making Test Part A, Time to Completion

The Trail Making Test Part A, time to completion assesses psychomotor speed and visual scanning with scores ranging from 1 to 150 seconds. Higher scores indicate worse performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · seconds to complete
Cognition/Functional Status - Change on the Trail Making Test Part A, Time to Completion
seconds to completeRAPA Intervention
Cognition/Functional Status - Change on the Trail Making Test Part A, Time to Completion3.09 ± 3.15
SecondaryCognition/Functional Status - Change Trail Making Test Part B, Time to Completion

The Trail Making Test Part B, time to completion assesses attentional shifting with scores ranging from 1 to 300 seconds. Higher scores indicate worse performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · seconds to complete
Cognition/Functional Status - Change Trail Making Test Part B, Time to Completion
seconds to completeRAPA Intervention
Cognition/Functional Status - Change Trail Making Test Part B, Time to Completion26.69 ± 14.97
SecondaryCognition/Functional Status - Change on Phonemic Fluency

The Phonemic fluency test assesses speeded word generation to a phonemic cue. Scores begin at 0 with no upper limit. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on Phonemic Fluency
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on Phonemic Fluency1.80 ± 3.71
SecondaryCognition/Functional Status - Change on Semantic Fluency

The Semantic fluency test assesses speeded word generation to a semantic cue. Scores begin at 0 with no upper limit. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on Semantic Fluency
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on Semantic Fluency1.10 ± 4.18
SecondaryCognition/Functional Status - Change on the Multilingual Naming Test

The Multilingual Naming Test assesses confrontation naming. Scores range from 0 to 32 and higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Multilingual Naming Test
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Multilingual Naming Test1.50 ± 4.67
SecondaryCognition/Functional Status - Change on the Hayling, Total Errors

The Hayling assesses response inhibition errors. Scores range from 0 to 30 and higher scores indicate worse performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Hayling, Total Errors
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Hayling, Total Errors0.001 ± 0.78
SecondaryCognition/Functional Status - Change on Grip Strength, Dominant Hand

The grip strength, dominant hand assesses grip strength in kilograms. Values begin at 0 with no upper limit. Higher scores indicate better performance Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · kilograms
Cognition/Functional Status - Change on Grip Strength, Dominant Hand
kilogramsRAPA Intervention
Cognition/Functional Status - Change on Grip Strength, Dominant Hand0.30 ± 2.10
SecondaryCognition/Functional Status - Change on Grip Strength, Non-dominant Hand

The grip strength, non-dominant hand assesses grip strength in kilograms. Values begin at 0 with no upper limit. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · kilograms
Cognition/Functional Status - Change on Grip Strength, Non-dominant Hand
kilogramsRAPA Intervention
Cognition/Functional Status - Change on Grip Strength, Non-dominant Hand-0.25 ± 3.30
SecondaryCognition/Functional Status - Change on the Geriatric Depression Scale 15-item

The Geriatric Depression Scale 15-item assesses depressive symptomatology. Scores range from 0 to 15 and higher scores indicate worse outcomes. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Geriatric Depression Scale 15-item
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Geriatric Depression Scale 15-item0.10 ± 1.73
SecondaryCognition/Functional Status - Change on the Functional Activities Questionnaire

The Functional Activities Questionnaire assesses functional status for independent activities of daily living. Scores range from 0 to 30 and higher scores indicate worse outcomes. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Functional Activities Questionnaire
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Functional Activities Questionnaire-0.10 ± 4.36
SecondaryCognition/Functional Status - Change on the Neuropsychiatric Inventory Questionnaire

The Neuropsychiatric Inventory Questionnaire assesses neuropsychiatric symptoms. Scores range from 0 to 12 and higher scores indicate worse outcomes. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Cognition/Functional Status - Change on the Neuropsychiatric Inventory Questionnaire
score on a scaleRAPA Intervention
Cognition/Functional Status - Change on the Neuropsychiatric Inventory Questionnaire0.70 ± 2.83

Adverse events

Collected over 8 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
RAPA Intervention0/10 (0%)1/10 (10%)10/10 (100%)
Most frequent serious events
Most frequent serious events
EventRAPA Intervention
Altered Mental StatusNervous system disorders1/10
Most frequent other events
Showing 10 of 13
Most frequent other events
EventRAPA Intervention
Leg edemaBlood and lymphatic system disorders2/10
FallGeneral disorders2/10
Intermittent RashSkin and subcutaneous tissue disorders1/10
HeadacheNervous system disorders1/10
Urinary retentionRenal and urinary disorders1/10
HyperkalemiaBlood and lymphatic system disorders1/10
Upper respiratory infectionRespiratory, thoracic and mediastinal disorders1/10
Skin infectionSkin and subcutaneous tissue disorders1/10
EmesisGastrointestinal disorders1/10
CoughRespiratory, thoracic and mediastinal disorders1/10

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)RAPA Intervention
<=18 years0
Between 18 and 65 years0
>=65 years10
Age, Continuous
Age, Continuous(years)RAPA Intervention
Mean74 ± 4
Sex: Female, Male
Sex: Female, Male(Participants)RAPA Intervention
Female6
Male4
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)RAPA Intervention
Hispanic or Latino0
Not Hispanic or Latino10
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)RAPA Intervention
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White10
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)RAPA Intervention
United States10
Diagnosis
Diagnosis(Participants)RAPA Intervention
Mild cognitive impairment6
Early-stage dementia4
08

Study locations

1 site
  • UTHSA McDermott Clinical Sciences Building
    San Antonio, Texas 78229, United States
09

References and documents

Publications

  • Gonzales MM, Garbarino VR, Kautz TF, Song X, Lopez-Cruzan M, Linehan L, Van Skike CE, De Erausquin GA, Galvan V, Orr ME, Musi N, He Y, Bateman RJ, Wang CP, Seshadri S, Kraig E, Kellogg D Jr. Rapamycin treatment for Alzheimer's disease and related dementias: a pilot phase 1 clinical trial. Commun Med (Lond). 2025 May 20;5(1):189. doi: 10.1038/s43856-025-00904-9. PubMed 40394335 ↗

Study documents

  • Protocol and statistical analysis plan · Jun 18, 2021
  • Informed consent form · Jun 18, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — The Institution, Sponsor or respective designees may review results prior to presenting or publishing the results of a scientific investigation involving this Study in accordance with ICJME guidelines and institutional requirements.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form

Time frame: After publication in a peer reviewed journal

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 8, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04200911
Lead sponsor
The University of Texas Health Science Center at San Antonio
Collaborators
National Center for Advancing Translational Sciences (NCATS)
Responsible party
Sponsor
First posted
Dec 16, 2019
Start date
Jun 1, 2020
Primary completion
Jan 13, 2022
Completion
Jan 13, 2022
Results posted
Mar 21, 2023
Last update
Jan 8, 2025

Study contacts

Mitzi Gonzales, PhD
principal investigator · The University of Texas Health Science Center at San Antonio

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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