NCT04552795: ART-AD

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

Completed Phase 1, PHASE2 Results posted Last updated 9 August 2024

What this trial tests

Phase 1, PHASE2 trial testing 3TC in Alzheimer Disease, Early Onset in 12 participants. Completed in 4 November 2023.

Timeline

15 February 2021

Primary endpoint
4 May 2023

4 November 2023

Quick facts

Lead sponsor	The University of Texas Health Science Center at San Antonio
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	12
Start date	15 February 2021
Primary completion	4 May 2023
Estimated completion	4 November 2023
Sites	3 locations across United States

Drugs / interventions tested

• 3TC — full drug profile →

Conditions studied

• Alzheimer Disease, Early Onset — all drugs for Alzheimer Disease, Early Onset →

Sponsor

The University of Texas Health Science Center at San Antonio

Who can join

Adults 50 to 80, any sex, with Alzheimer Disease, Early Onset. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Reverse Transcriptase Activity From Baseline to 24 Weeks in Plasma of Study Participants Primary · 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.

Group	Value	95% CI
Open-Label 3TC	-0.0074	± 0.03

3TC CNS Penetration Primary · 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).

Group	Value	95% CI
Open-Label 3TC	0.502	0.0215 – 0.850

Change in Dementia Severity From Baseline to Week 24 of Treatment Based on the PACC-5 Z-score Secondary · Baseline to 24 weeks

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

Group	Value	95% CI
Baseline	-1.59	-2 – -0.59
POST-Treatment	-1.59	-2 – -1.2

Incidence of Treatment-Emergent Adverse Events Secondary · Baseline to Week 24

Incidence of adverse and serious adverse events potentially due to study drug

Group	Value	95% CI
Open-Label 3TC	1
Open-Label 3TC	11

Incidence of Treatment-Emergent Abnormal Vital Signs Secondary · Baseline to Week 24

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.

Group	Value	95% CI
Open-Label 3TC	0

Adverse events — posted to ClinicalTrials.gov

Time frame: 28 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Open-Label 3TC

Serious: 1/12 (8%)

Deaths: 0/12

Serious adverse events (1 terms)

Reaction	System	Open-Label 3TC
Gastrointestinal bleeding	Gastrointestinal disorders	—

Other adverse events (4 terms — click to expand)

Reaction	System	Open-Label 3TC
SARS-CoV-2 Infection	Infections and infestations	—
Mild headache	Nervous system disorders	—
Mild fatigue	Nervous system disorders	—
Mild muscle pain	Musculoskeletal and connective tissue disorders	—

Most-reported serious reactions: Gastrointestinal bleeding.

Data from ClinicalTrials.gov NCT04552795 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Alzheimer's disease drug development pipeline: 2022.
   Cummings J, Lee G, Nahed P, Kambar MEZN, et al · · 2022 · cited 369× · PMID 35516416 · DOI 10.1002/trc2.12295
2. Alzheimer's disease drug development pipeline: 2023.
   Cummings J, Zhou Y, Lee G, Zhong K, et al · · 2023 · cited 326× · PMID 37251912 · DOI 10.1002/trc2.12385
3. Alzheimer's disease drug development pipeline: 2021.
   Cummings J, Lee G, Zhong K, Fonseca J, et al · · 2021 · cited 312× · PMID 34095440 · DOI 10.1002/trc2.12179
4. Pathological mechanisms and therapeutic strategies for Alzheimer's disease.
   Ju Y, Tam KY. · · 2022 · cited 260× · PMID 34380884 · DOI 10.4103/1673-5374.320970
5. Alzheimer's disease drug development pipeline: 2024.
   Cummings J, Zhou Y, Lee G, Zhong K, et al · · 2024 · cited 209× · PMID 38659717 · DOI 10.1002/trc2.12465
6. From geroscience to precision geromedicine: Understanding and managing aging.
   Kroemer G, Maier AB, Cuervo AM, Gladyshev VN, et al · · 2025 · cited 139× · PMID 40250404 · DOI 10.1016/j.cell.2025.03.011
7. Alzheimer's Disease: Novel Targets and Investigational Drugs for Disease Modification.
   Cummings JL, Osse AML, Kinney JW. · · 2023 · cited 75× · PMID 37728864 · DOI 10.1007/s40265-023-01938-w
8. Pathogenic tau accelerates aging-associated activation of transposable elements in the mouse central nervous system.
   Ramirez P, Zuniga G, Sun W, Beckmann A, et al · · 2022 · cited 61× · PMID 34670118 · DOI 10.1016/j.pneurobio.2021.102181