A Phase 1/2 interventional study of 3TC in Alzheimer Disease, Early Onset, sponsored by The University of Texas Health Science Center at San Antonio. Completed at 3 sites in United States. Open to participants aged 50 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-08-09.
Sponsored by The University of Texas Health Science Center at San Antonio · Phase 1/2, Interventional, and Treatment
The objective of the study is to evaluate the ability of (-)-L-2',3'-dideoxy-3'-thiacytidine (3TC) to engage its intended target, penetrate the central nervous system (CNS), suppress neurodegeneration, and assess safety and tolerability in patients with early stage Alzheimer's disease. This study will provide the initial data on target engagement and Alzheimer's disease-relevant outcomes for future trials.
This open label study of 3TC will collect initial proof-of-concept data on 3TC target engagement, CNS penetration, efficacy and safety in older adults with early stage Alzheimer's disease. If successful, data will be used to design a larger phase 2 clinical trial. The investigators aim to I) Quantify 3TC target engagement and CNS penetration, II) Determine if 3TC suppresses Alzheimer's disease-relevant outcomes, and III) Assess the safety and tolerability of 3TC in older individuals with early Alzheimer's disease. The study will consist of a screening/baseline period of 30 days pre-treatment, a 24-week open label treatment period, and a follow up visit one month following treatment. Visits to the clinic include a pre-treatment screening visit that includes a comprehensive neuropsychological exam, a tablet-based neuropsychological exam, and a blood draw. For eligible participants, a lumbar puncture will be performed on day one of treatment. Participants will visit the clinic on day one of treatment and at weeks 8, 16, and 24 of treatment to complete medication checks, physical examinations, tablet-based cognitive screening, and blood draw. At week 24 of treatment, patients will undergo a post-treatment comprehensive neuropsychological exam, a lumbar puncture to collect cerebrospinal fluid, and a blood draw. One month after the final dose of medication, participants will return to the clinic for a final safety assessment and disenrollment.
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 12 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →The University of Texas Health Science Center at San Antonio is the lead sponsor of 435 studies on the registry; 88 are open to participants now.
Of its 62 completed or terminated interventional studies of FDA-regulated products, 31 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
12 subjects will receive 3TC, 300-mg, daily for 24 weeks.
Drug: 3TC
12 subjects will be administered 3TC, 300mg once daily, via an oral tablet for 24 weeks.
Also known as: Epivir, lamivudine
Change in Reverse Transcriptase Activity From Baseline to 24 Weeks in Plasma of Study Participants
The extent of 3TC target engagement was measured by calculating the change in reverse transcriptase activity in plasma of participants at baseline compared to week 24 using a modified version of the EnzCheck Reverse Transcriptase (RT) Assay.
Time frame: Baseline to 24 weeks
3TC CNS Penetration
CNS penetration was calculated based on the ratio of CSF to plasma levels of 3TC after 24 weeks of 3TC using High Performance Liquid Chromatography with tandem Mass Spectrometry (HPLC/MS/MS).
Time frame: 24 weeks
Change in Dementia Severity From Baseline to Week 24 of Treatment Based on the PACC-5 Z-score
The Preclinical Alzheimer Cognitive Composite (PACC-5) score is calculated as a mean normative Z-score across five measures, including MMSE (0-30), Logical Memory Delayed Recall (0-25), Digit-Symbol Coding Test (0-93), Category Fluency, and Free and Cued Selective Reminding Test (0-96). Although typically relegated to individuals with prodromal and asymptomatic disease, the PACC-5 was included given its sensitivity to Alzheimer's disease-specific cognitive change.To calculate the Z score for each patient; the formula is Z = (x - M)/SD, where x is the patient's verbal memory raw score and M and SD are the estimates from the previous step. Positive Z values indicate scores that are greater than the mean of the pooled sample, and negative values indicate scores that are less than the pooled mean.A Z-score of zero represents the mean for this study population. Negative values mean a worse outcome than the standard population.
Time frame: Baseline to 24 weeks
Incidence of Treatment-Emergent Adverse Events
Incidence of adverse and serious adverse events potentially due to study drug
Time frame: Baseline to Week 24
Incidence of Treatment-Emergent Abnormal Vital Signs
Blood pressure, heart rate, temperature, and respiration, are measured and any significant change of any of these vital signs that show a significant change from the baseline value are reported as an event.
Time frame: Baseline to Week 24
Participants were recruited from University of Texas Health San Antonio outpatient clinics and through local flier/newspaper advertisements.
| Milestone | Open-Label 3TC |
|---|---|
| Started | 12 |
| Completed | 12 |
| Not completed | 0 |
The extent of 3TC target engagement was measured by calculating the change in reverse transcriptase activity in plasma of participants at baseline compared to week 24 using a modified version of the EnzCheck Reverse Transcriptase (RT) Assay.
| Enzyme units | Open-Label 3TC |
|---|---|
| Change in Reverse Transcriptase Activity From Baseline to 24 Weeks in Plasma of Study Participants | -0.0074 ± 0.03 |
CNS penetration was calculated based on the ratio of CSF to plasma levels of 3TC after 24 weeks of 3TC using High Performance Liquid Chromatography with tandem Mass Spectrometry (HPLC/MS/MS).
| ng/mL | Open-Label 3TC |
|---|---|
| 3TC CNS Penetration | 0.502 (0.0215 to 0.850) |
The Preclinical Alzheimer Cognitive Composite (PACC-5) score is calculated as a mean normative Z-score across five measures, including MMSE (0-30), Logical Memory Delayed Recall (0-25), Digit-Symbol Coding Test (0-93), Category Fluency, and Free and Cued Selective Reminding Test (0-96). Although typically relegated to individuals with prodromal and asymptomatic disease, the PACC-5 was included given its sensitivity to Alzheimer's disease-specific cognitive change.To calculate the Z score for each patient; the formula is Z = (x - M)/SD, where x is the patient's verbal memory raw score and M and SD are the estimates from the previous step. Positive Z values indicate scores that are greater than the mean of the pooled sample, and negative values indicate scores that are less than the pooled mean.A Z-score of zero represents the mean for this study population. Negative values mean a worse outcome than the standard population.
| Z-score | Baseline | POST-Treatment |
|---|---|---|
| Change in Dementia Severity From Baseline to Week 24 of Treatment Based on the PACC-5 Z-score | -1.59 (-2 to -0.59) | -1.59 (-2 to -1.2) |
Incidence of adverse and serious adverse events potentially due to study drug
| Participants | Open-Label 3TC |
|---|---|
| Gastrointestinal bleeding due to peptic ulcer | 1 |
| No adverse events | 11 |
Blood pressure, heart rate, temperature, and respiration, are measured and any significant change of any of these vital signs that show a significant change from the baseline value are reported as an event.
| Events | Open-Label 3TC |
|---|---|
| Incidence of Treatment-Emergent Abnormal Vital Signs | 0 |
Collected over 28 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Open-Label 3TC | 0/12 (0%) | 1/12 (8.3%) | 2/12 (16.7%) |
| Event | Open-Label 3TC |
|---|---|
| Gastrointestinal bleedingGastrointestinal disorders | 1/12 |
| Event | Open-Label 3TC |
|---|---|
| SARS-CoV-2 InfectionInfections and infestations | 2/12 |
| Mild headacheNervous system disorders | 2/12 |
| Mild fatigueNervous system disorders | 1/12 |
| Mild muscle painMusculoskeletal and connective tissue disorders | 1/12 |
| Age, Customized(years) | Open-Label 3TC |
|---|---|
| Average age (min, max) | 69.4 (52 to 83) |
| Age, Customized(Participants) | Open-Label 3TC |
|---|---|
| Age group — <= 65 years of age | 3 |
| Age group — 65 - 74 years of age | 5 |
| Age group — 75 - 84 years of age | 4 |
| Sex: Female, Male(Participants) | Open-Label 3TC |
|---|---|
| Female | 9 |
| Male | 3 |
| Race/Ethnicity, Customized(Participants) | Open-Label 3TC |
|---|---|
| Race — White, non-Hispanic | 9 |
| Race — White, Hispanic | 1 |
| Race — African American | 1 |
| Race — Asian | 1 |
| Education Level(years) | Open-Label 3TC |
|---|---|
| Mean | 15.3 ± 2.4 |
| Past Medical History(Participants) | Open-Label 3TC |
|---|---|
| <= 1 Comorbidities | 2 |
| 2+ Comorbidities | 10 |
| Duration of Symptoms Prior to Trial(Participants) | Open-Label 3TC |
|---|---|
| <= 1 year | 1 |
| 1-2 years | 2 |
| 3+ years | 2 |
| Unknown | 7 |
| Average BMI(kg/m^2) | Open-Label 3TC |
|---|---|
| Mean | 25.2 ± 4.6 |
1 further baseline measures are reported on the registry.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Protocol, Published Data
Supporting information: Study protocol
This study is completed, as verified in Jul 2024. You cannot join it, but the record below documents what was studied.
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The University of Texas Health Science Center at San Antonio