Alzheimer Disease, Early OnsetPhase 1/2ART-ADNCT04552795

Pilot Study to Investigate the Safety and Feasibility of AntiRetroviral Therapy for Alzheimer's Disease

A Phase 1/2 study testing 3TC in people with Alzheimer Disease, Early Onset, run by The University of Texas Health Science Center at San Antonio at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 50 to 80 years
Conditions the study is for: Alzheimer Disease, Early Onset
What is being tested?: 3TC
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 3 sitesUnited States
Study dates: 15 Feb 2021to 4 Nov 2023
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 50 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Aged 50-99 years
Clinical diagnosis of early Alzheimer's disease (Clinical Dementia Rating (CDR) = 0.5, Mini-Mental State Exam (MMSE) = 24-30)
If using drugs to treat symptoms related to Alzheimer's disease, doses must be stable for at least eight weeks prior to screening visit 1
Labs: Adequate blood cell counts (white blood cells: 4,000-111,000 cells per microliter (cells/mcL); absolute neutrophil count: 1,800-8,700 cells/mcL; platelets: 120-500 K/µL; hemoglobin 12.0-17.5 grams/dL); LFT's within 2x normal value; creatinine clearance test (CrCl) ≥ 50 mL/min; cholesterol (≤260 mg/dl), triglycerides≤ 400 mg/dl), and glucose control (HbA1c ≤ 8%). Prothrombin time/partial thromboplastin time/international normalized ratio (PT/PTT/INR) within normal limits
Body mass index (BMI) within range of 19 - 35 kg/m2
Must have a reliable informant or caregiver
Participants must have no plans to travel that interfere with study visits

Who cannot join

Any medical or neurologic condition (other than Alzheimer's Disease) that might be a contributing cause of the subject's cognitive impairment
Clinically significant unstable psychiatric illness in the past six months
Significant hearing, vision, or motor deficits that interfere with participation
Alcohol or drug abuse/dependence in the past six months
Stroke, transient ischemic attack, or unexplained loss of consciousness in the past six months
Unstable angina, myocardial infarction, advanced chronic heart failure, or clinically significant conduction abnormalities within the past six months

Show all 15Show fewer

Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
Diagnosis of HIV infection or AIDS (CD4 count < 200), HIV/Hepatitis B Virus (HBV) co-infection, HBV or human T-cell leukemia virus infection
History of impaired renal or liver function
Current use of memantine or sorbitol-containing products
Individuals with HIV, HBV, or who have current/previous use of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) or non-NRTIs.
Poorly controlled blood pressure (BP) (systolic BP > 160, diastolic BP > 90 mmHg)
Uncontrolled diabetes (HbA1c > 8%, or the current use of insulin)
Significant systematic illness or infection in the past 30 days
Pregnant women

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases
San Antonio, Texas, 78229
Sam and Ann Barshop Institute for Longevity & Aging Studies
San Antonio, Texas, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: Pilot Study to Investigate the Safety and Feasibility of AntiRetroviral Therapy for Alzheimer's Disease (ART-AD)

Read the detailed description

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.

Conditions: Alzheimer Disease, Early Onset
Being tested: 3TC
Medical subject headings: Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

3TCDrug
Also called Epivir, lamivudine
12 subjects will be administered 3TC, 300mg once daily, via an oral tablet for 24 weeks.

Study groups in NCT04552795
Study group	Role	What they receive
Open-Label 3TC	Experimental	12 subjects will receive 3TC, 300-mg, daily for 24 weeks. Receives: Drug: 3TC

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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).
Measured: 24 weeks

Secondary outcomes (3)

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.
Measured: Baseline to 24 weeks
Incidence of Treatment-Emergent Adverse Events
Incidence of adverse and serious adverse events potentially due to study drug
Measured: 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.
Measured: Baseline to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Feb 20214 Nov 2023

First posted17 Sep 2020
Study start15 Feb 2021
Primary completion4 May 2023
Study completion4 Nov 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Alzheimer Disease, Early OnsetStudies of the same condition, open and under way.
More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Open-label, one arm study.
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04552795
Sponsor's protocol ID: HSC20200396H
Acronym: ART-AD
Status last verified: Jul 2024
First submitted: 11 Aug 2020
Last updated: 9 Aug 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Protocol, Published Data

Publications

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.
PubMed 40368603

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study to Investigate the Safety and Feasibility of AntiRetroviral Therapy for Alzheimer's Disease (ART-AD)
ClinicalTrials.gov ID: NCT04552795
Acronym / sponsor ID: ART-AD / HSC20200396H
Conditions: Alzheimer Disease, Early Onset
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: The University of Texas Health Science Center at San AntonioUniversity, hospital or other
Collaborators: Owens Medical Research Foundation
Study start: 15 Feb 2021 (actual)
Primary completion: 4 May 2023 (actual)
Study completion: 4 Nov 2023 (actual)
First posted: 17 Sep 2020 (actual)
Results: Posted 9 Aug 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Open-label, one arm study.

Arm	Type	Receives
Open-Label 3TC	Experimental	Drug: 3TC12 subjects will receive 3TC, 300-mg, daily for 24 weeks.

Who may qualify

Ages: 50 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Aged 50-99 years
Clinical diagnosis of early Alzheimer's disease (Clinical Dementia Rating (CDR) = 0.5, Mini-Mental State Exam (MMSE) = 24-30)
If using drugs to treat symptoms related to Alzheimer's disease, doses must be stable for at least eight weeks prior to screening visit 1
Labs: Adequate blood cell counts (white blood cells: 4,000-111,000 cells per microliter (cells/mcL); absolute neutrophil count: 1,800-8,700 cells/mcL; platelets: 120-500 K/µL; hemoglobin 12.0-17.5 grams/dL); LFT's within 2x normal value; creatinine clearance test (CrCl) ≥ 50 mL/min; cholesterol (≤260 mg/dl), triglycerides≤ 400 mg/dl), and glucose control (HbA1c ≤ 8%). Prothrombin time/partial thromboplastin time/international normalized ratio (PT/PTT/INR) within normal limits
Body mass index (BMI) within range of 19 - 35 kg/m2

Key exclusion criteria (15 listed)

Any medical or neurologic condition (other than Alzheimer's Disease) that might be a contributing cause of the subject's cognitive impairment
Clinically significant unstable psychiatric illness in the past six months
Significant hearing, vision, or motor deficits that interfere with participation
Alcohol or drug abuse/dependence in the past six months
Stroke, transient ischemic attack, or unexplained loss of consciousness in the past six months

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
3TCAlso: Epivir, lamivudine12 subjects will be administered 3TC, 300mg once daily, via an oral tablet for 24 weeks.	Drug	Open-Label 3TC

Primary outcome

Change in Reverse Transcriptase Activity From Baseline to 24 Weeks in Plasma of Study Participants
Time frame: Baseline to 24 weeks
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.
3TC CNS Penetration
Time frame: 24 weeks
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).

3 secondary outcomes

Change in Dementia Severity From Baseline to Week 24 of Treatment Based on the PACC-5 Z-score
Time frame: Baseline to 24 weeks
Incidence of Treatment-Emergent Adverse Events
Time frame: Baseline to Week 24
Incidence of Treatment-Emergent Abnormal Vital Signs
Time frame: Baseline to Week 24

Results and safety

Results posted to the registry on 9 Aug 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Open-Label 3TC	12	12

Primary outcome: Change in Reverse Transcriptase Activity From Baseline to 24 Weeks in Plasma of Study Participants

Time frame: Baseline to 24 weeks. Mean (Standard Error). Unit: Enzyme units

Measure	Open-Label 3TC n = 12
Value	-0.0074 (0.03)

Primary outcome: 3TC CNS Penetration

Time frame: 24 weeks. Mean (Inter-Quartile Range). Unit: ng/mL

Measure	Open-Label 3TC n = 7
Value	0.502 (0.0215 to 0.850)

Population analysed: Three subjects removed due to missed blood or CSF draw; one subject removed based on the ROUT method of outlier analysis.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 28 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Open-Label 3TC	1 of 12 (8.3%)	2 of 12 (16.7%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40368603Nicodemus 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.
Individual participant dataSharing planned: Yes. Protocol, Published Data

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bess Frost, PhD principal investigator

Univ of Texas Health Science Center at San Antonio

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing 3TC in people with Alzheimer Disease, Early Onset, run by The University of Texas Health Science Center at San Antonio at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Reverse Transcriptase Activity From Baseline to 24 Weeks in Plasma of Study Participants (time frame: Baseline to 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04552795, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.