A Phase 1/2 interventional study of Bryostatin 1 and Placebo in Alzheimer's Disease, sponsored by Neurotrope Bioscience, Inc.. Terminated at 1 site in United States. Open to participants aged 50 Years to 85 Years. Per ClinicalTrials.gov, last updated 2017-11-06.
Sponsored by Neurotrope Bioscience, Inc. · Phase 1/2, Interventional, and Treatment
This study is being done to evaluate the safety, tolerability and potential effectiveness of a new investigational drug, bryostatin 1, in patients with Alzheimer's disease (AD).
This study is a single center, randomized, double-blind, placebo-controlled, parallel groups trial in patients with AD. Each subject enrolled in the trial will be randomized to receive a single IV dose of 0 (placebo) or 25 μg/m2 bryostatin. A total of 15 subjects (5 in the placebo arm and 10 in the treatment arm) will be enrolled in the study. The study consists of screening evaluations and on study evaluations divided into two segments, an inpatient segment and an outpatient segment. The four-day inpatient segment will consist of baseline evaluations and a 1-hour IV infusion of study drug followed by evaluations at multiple evaluations over the first 72 hrs post dose. During the outpatient segment, patients will be followed for AEs and have a final evaluation at 2 weeks post dose and a 4-week telephone safety follow up. Evaluations will include safety, efficacy, pharmacokinetics, and pharmacodynamics as assessed by PKC activity
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 9 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →Neurotrope Bioscience, Inc. is the lead sponsor of 4 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
Drug: Bryostatin 1
single dose of placebo, intravenous infusion over 1 hour
Drug: Placebo
25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.
Placebo, single dose via intravenous infusion over 1 hour.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Evaluate the safety and tolerability of bryostatin 1 (hereinafter referred to as bryostatin) in patients with Alzheimer's Disease (AD) following a single intravenous (IV) dose.
Time frame: Within 2 weeks of study drug dosing
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
Hopkins Verbal Learning Test - Revised (HVLT-R) delayed recall; change from baseline. HVLT consists of a 12-item word list drawn from 3 semantic categories, presented in 3 learning trials. Score range = 0-12. The lower the number, the more impaired. Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Total Score Range: 0-20. Each portion of the drawing is scored 1 point for correctness and completeness and 1 point for being placed properly in relation to the rest of the drawing. Drawing and placement scores are summed for the item total. To obtain subtest total score, the drawing and placement scores are summed for each item. The lower the number, the more impaired.
Time frame: 48 hours post start of study drug infusion
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
HVLT-R (Hopkins Verbal Learning Test-Revised™) delayed recall (change from baseline). A 12-item word list: 3 learning trials. Score range = 0-12. The lower the number, the more impaired. Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Score Range: 0-20. The lower the number, the more impaired. Digit Symbol Coding (observed), Score range: 0-125. The lower the number, the more impaired. Clinical Dementia Rating- Sum of Boxes (CDR-SB, observed). Sum of 6 investigated domains (Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, Personal Care). Each subtest range is 0-3; Sum of all 6 subtest scores gives total CDR-SB score (range= 0-18).The higher the number, the more impaired. Mini Mental State Exam, version 2 (MMSE-2), change from baseline. The MMSE-2 measures aspects of cognitionon a scale of 0-30. Lower scores indicate greater cognitive impairment.
Time frame: Specified timepoints within 2 weeks post study drug infusion
Pharmacokinetic Parameters of Bryostatin.
Preliminary evaluation of pharmacokinetics and pharmacodynamics (Cmax, Tmax, AUClast).
Time frame: Bryostatin plasma concentration pre-dose and at 15 min, 30 min, 1 hr, 1.5 hr, 2hr, 3hr and 6rs post dose.
| Milestone | Bryostatin 1 | Placebo |
|---|---|---|
| Started | 6 | 3 |
| Completed | 6 | 3 |
| Not completed | 0 | 0 |
Evaluate the safety and tolerability of bryostatin 1 (hereinafter referred to as bryostatin) in patients with Alzheimer's Disease (AD) following a single intravenous (IV) dose.
| event | Bryostatin 1 | Placebo |
|---|---|---|
| Dizziness | 0 | 1 |
| Headache | 1 | 1 |
| Rash Papular | 0 | 1 |
Hopkins Verbal Learning Test - Revised (HVLT-R) delayed recall; change from baseline. HVLT consists of a 12-item word list drawn from 3 semantic categories, presented in 3 learning trials. Score range = 0-12. The lower the number, the more impaired. Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Total Score Range: 0-20. Each portion of the drawing is scored 1 point for correctness and completeness and 1 point for being placed properly in relation to the rest of the drawing. Drawing and placement scores are summed for the item total. To obtain subtest total score, the drawing and placement scores are summed for each item. The lower the number, the more impaired.
| units on a scale, change from baseline | Bryostatin 1 | Placebo |
|---|---|---|
| HVLT-R at 48hrs (change from baseline) | 1.3 ± 2.16 | 3.7 ± 1.15 |
| RBANS figure recall at 48hrs (CBL) | 4.5 ± 4.14 | 6.7 ± 3.06 |
HVLT-R (Hopkins Verbal Learning Test-Revised™) delayed recall (change from baseline). A 12-item word list: 3 learning trials. Score range = 0-12. The lower the number, the more impaired. Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Score Range: 0-20. The lower the number, the more impaired. Digit Symbol Coding (observed), Score range: 0-125. The lower the number, the more impaired. Clinical Dementia Rating- Sum of Boxes (CDR-SB, observed). Sum of 6 investigated domains (Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, Personal Care). Each subtest range is 0-3; Sum of all 6 subtest scores gives total CDR-SB score (range= 0-18).The higher the number, the more impaired. Mini Mental State Exam, version 2 (MMSE-2), change from baseline. The MMSE-2 measures aspects of cognitionon a scale of 0-30. Lower scores indicate greater cognitive impairment.
| units on a scale | Bryostatin 1 | Placebo |
|---|---|---|
| HVLT-R 24hr Delayed Recall (change from baseline) | 0.5 ± 3.27 | 1.3 ± 2.52 |
| HVLT-R 2 Wks Delayed Recall (change from baseline) | 0.3 ± 1.63 | 2.3 ± 2.52 |
| RBANS 24hr Figure Recall (change from baseline) | 4.7 ± 4.76 | 6.0 ± 2.65 |
| RBANS 2 Wks Figure Recall (CBL) | 4.2 ± 5.60 | 7.3 ± 3.06 |
| HVLT-R delayed recall of stimuli at 48hr (CBL) | -1.2 ± 1.17 | 2.7 ± 2.08 |
| Digit Symbol Coding baseline (observed) | 32.2 ± 9.13 | 42.3 ± 12.50 |
| Digit Symbol Coding 24hrs post start of infusion | 36.0 ± 10.75 | 49.0 ± 4.58 |
| Digit Symbol Coding 48hrs post start of infusion | 37.3 ± 11.64 | 53.7 ± 4.73 |
| Digit Symbol Coding 2 wks post start of infusion | 38.3 ± 7.61 | 52.7 ± 6.66 |
| CDR, CDR-SB baseline (observed) | 1.3 ± 0.98 | 0.7 ± 0.29 |
| CDR, CDR-SB 2wks (observed) | 1.5 ± 1.00 | 0.7 ± 0.29 |
| MMSE-2 3hrs post start of inf (change) | 1.8 ± 1.72 | -1.0 ± 2.65 |
| Digit Symbol Coding baseline (observed) | 32.2 ± 9.13 | 42.3 ± 12.50 |
| Digit Symbol Coding 3hrs post start of inf (observ | 32.7 ± 6.86 | 45.3 ± 11.50 |
| MMSE-2 at 72hrs (change from Baseline) | 2.6 ± 1.52 | 3.3 ± 2.52 |
| MMSE-2 at 2wks (change from Baseline) | 3.3 ± 1.86 | 4.7 ± 1.15 |
Preliminary evaluation of pharmacokinetics and pharmacodynamics (Cmax, Tmax, AUClast).
| bryostatin plasma concentration (ng/mL) | Bryostatin 1 | Placebo |
|---|---|---|
| predose Bryostatin Plasma Concentration (ng/mL) | 0.0 ± 0.0 | — |
| Concentration 15 min post (ng/mL) | 0.880 ± 0.133 | — |
| Concentration 30 min post (ng/mL) | 0.941 ± 0.168 | — |
| Concentration 1 hr post (ng/mL) | 1.04 ± 0.309 | — |
| Concentration 1.5 hrs post (ng/mL) | 0.181 ± 0.148 | — |
| Concentration 2 hrs post (ng/mL) | 0.0702 ± 0.109 | — |
| Concentration 3 hrs post (ng/mL) | 0.0 ± 0.0 | — |
| Concentration 6 hrs post (ng/mL) | 0.0 ± 0.0 | — |
| Cmax (ng/mL) | 1.09 ± 0.246 | — |
Collected over Adverse event collection began 28 days prior to dosing and continued until 4 weeks after dosing. Ongoing AEs were followed until resolved or stabilized.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Bryostatin 1 | — | 0/6 (0%) | 1/6 (16.7%) |
| Placebo | — | 0/3 (0%) | 3/3 (100%) |
| Event | Bryostatin 1 | Placebo |
|---|---|---|
| DizzinessNervous system disorders | 0/6 | 1/3 |
| HeadacheGeneral disorders | 1/6 | 1/3 |
| Rash PapularSkin and subcutaneous tissue disorders | 0/6 | 1/3 |
| Age, Categorical(Participants) | Bryostatin 1 | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 1 | 0 | 1 |
| >=65 years | 5 | 3 | 8 |
| Age, Continuous(years) | Bryostatin 1 | Placebo | Total |
|---|---|---|---|
| Mean | 72.5 ± 8.04 | 70.7 ± 7.23 | 71.9 ± 7.37 |
| Sex: Female, Male(Participants) | Bryostatin 1 | Placebo | Total |
|---|---|---|---|
| Female | 4 | 1 | 5 |
| Male | 2 | 2 | 4 |
| Region of Enrollment(participants) | Bryostatin 1 | Placebo | Total |
|---|---|---|---|
| United States | 6 | 3 | 9 |
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Neurotrope Bioscience, Inc.