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| Name | Class |
|---|---|
| Owens Medical Research Foundation | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open-Label 3TC | Experimental | 12 subjects will receive 3TC, 300-mg, daily for 24 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3TC | Drug | 12 subjects will be administered 3TC, 300mg once daily, via an oral tablet for 24 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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). | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bess Frost, PhD | Univ of Texas Health Science Center at San Antonio | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases | San Antonio | Texas | 78229 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40368603 | Derived | Nicodemus J, Liu CS, Ransom L, Tan V, Romanow W, Jimenez N, Chun J. Sequence Diversity and Encoded Enzymatic Differences of Monocistronic L1 ORF2 mRNA Variants in the Aged Normal and Alzheimer's Disease Brain. J Neurosci. 2025 Jun 18;45(25):e2298242025. doi: 10.1523/JNEUROSCI.2298-24.2025. |
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Protocol, Published Data
After study completion, upon publication of data and on ClinicalTrials.gov 1 year after primary completion date of study.
Data will be analyzed by the study investigators.
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Participants were recruited from University of Texas Health San Antonio outpatient clinics and through local flier/newspaper advertisements.
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| ID | Title | Description |
|---|---|---|
| FG000 | Open-Label 3TC | 12 subjects will be administered a 300mg once daily oral tablet of 3TC for 24 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Open-Label 3TC | 12 subjects will receive 3TC, 300-mg, daily for 24 weeks. 3TC: 12 subjects will be administered 3TC, 300mg once daily, via an oral tablet for 24 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Error | Enzyme units | Baseline to 24 weeks |
|
|
28 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Open-Label 3TC | 12 subjects administered once daily 300 mg 3TC for 24 weeks | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal bleeding | Gastrointestinal disorders | Non-systematic Assessment | Gastrointestinal bleeding due to a peptic ulcer; subject was on daily aspirin |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| SARS-CoV-2 Infection | Infections and infestations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bess Frost, PhD | UT Health San Antonio | 210-562-5037 | bfrost@uthscsa.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 8, 2021 | Mar 13, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D019259 | Lamivudine |
| ID | Term |
|---|---|
| D016047 | Zalcitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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Open-label, one arm study.
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| Baseline to 24 weeks |
| Incidence of Treatment-Emergent Adverse Events | Incidence of adverse and serious adverse events potentially due to study drug | 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. | Baseline to Week 24 |
| Sam and Ann Barshop Institute for Longevity & Aging Studies |
| San Antonio |
| Texas |
| 78229 |
| United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Education Level | Mean | Standard Deviation | years |
|
| Past Medical History | Count of Participants | Participants |
|
| Duration of Symptoms Prior to Trial | Count of Participants | Participants |
|
| Average BMI | Mean | Standard Deviation | kg/m^2 |
|
| Concurrent Treatment with Donepezil | Count of Participants | Participants |
|
|
| Primary | 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). | Three subjects removed due to missed blood or CSF draw; one subject removed based on the ROUT method of outlier analysis. | Posted | Mean | Inter-Quartile Range | ng/mL | 24 weeks |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | Z-score | Baseline to 24 weeks |
|
|
|
| Secondary | Incidence of Treatment-Emergent Adverse Events | Incidence of adverse and serious adverse events potentially due to study drug | Posted | Count of Participants | Participants | Baseline to Week 24 |
|
|
|
| Secondary | 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. | Posted | Number | Events | Baseline to Week 24 |
|
|
|
| 12 |
| 1 |
| 12 |
| 2 |
| 12 |
|
| Mild headache | Nervous system disorders | Systematic Assessment |
|
| Mild fatigue | Nervous system disorders | Systematic Assessment |
|
| Mild muscle pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
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| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D015224 | Dideoxynucleosides |