Safety of NRTIs for Alzheimer's patients in Singapore

A Phase 1b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of Emtricitabine and Descovy in Patients With Mild Cognitive Impairment.

This trial will test emtricitabine or Descovy versus placebo in people with mild cognitive impairment or early Alzheimer's to see if these reverse transcriptase inhibitors are safe and tolerable.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 50 Years to 85 Years
• Sex: All
• Sponsor: National University Hospital, Singapore (Academic / other)
• Locations: 1 site (Singapore)
• Trial ID: NCT07210528 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, single-site, randomized placebo-controlled safety trial conducted at National University Hospital in Singapore that gives emtricitabine or Descovy (TAF/FTC) to people with mild cognitive impairment or very early Alzheimer's. Participants are screened to exclude HIV or hepatitis B and must be able to provide informed consent; those already on acetylcholinesterase inhibitors or memantine are excluded. The study collects blood samples and performs neuropsychological testing while monitoring adverse events and tolerability. The primary focus is on short-term safety and tolerability in the target population rather than efficacy.

Who should consider this trial

Good fit: Adults with mild cognitive impairment or very mild Alzheimer's (MMSE ≥24; CDR-GS 0–0.5), able to consent, not taking acetylcholinesterase inhibitors or memantine, and who test negative for HIV and hepatitis B.

Not a fit: People with more advanced Alzheimer's, those currently on AChE inhibitors or memantine, or those with HIV or hepatitis B are excluded and unlikely to benefit from this Phase 1 safety-focused trial.

Why it matters

Potential benefit: If shown to be safe and tolerable in this population, these already-approved antiviral drugs could be repurposed to alter disease biology or slow progression in early Alzheimer's.

How similar studies have performed: Preclinical and genetic research suggests reverse transcriptase activity may contribute to Alzheimer's pathology, but clinical testing of reverse transcriptase inhibitors for Alzheimer's is novel and human efficacy data are very limited.

Eligibility criteria

Inclusion Criteria:

* MMSE score of 24 or above.
* CDR-GS of 0 or 0.5 (calculated by the QDRS)
* Diagnosed with MCI, determined by impairment in at least one domain of the neuropsychological test battery without significant dysfunction in activities of daily living OR MCI consistent with the NIA/AA diagnostic criteria.
* Does not have any medical condition (e.g. cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments.
* Willingness to provide blood sample and neuropsychological testing for the study.
* Ability for the patient to provide informed consent.

Exclusion Criteria:

* Patient who is receiving a prescription of acetylcholinesterase inhibitor (AChEI) and/or Memantine at screening or baseline.
* Patients with a history of HIV or HBV infection, or that test positive for HIV or HBV on screening.
* Pre-existing comorbidities such as Hepatits, cardiovascular disease, or renal insufficiency.
* History of Moderate to severe hepatic impairment indicated by screening AST or ALT \> 3x the upper limit of normal (ULN) or total bilirubin \> 2x ULN.
* Patients with severe renal impairment, or creatinine clearance ≤ 30 mL/min (calculated by Cockcroft-Gault formulae at screening).
* Co administration of nephrotoxic drugs.
* Current or previous RTi use within the last 2 years.
* Malignant neoplasm, and are undergoing active treatment.
* Participating in other interventional clinical trials during the course of the study.
* Documented history of lactic acidosis and severe hepatomegaly with steatosis.
* Documented history of osteoporosis.

Where this trial is running

Singapore

• National University Hospital — Singapore, Singapore (Recruiting)

Study contacts

• Principal investigator: Christopher Chen — National University Hospital, Singapore
• Study coordinator: Jit Hui Mark Lim

Conditions Mild Cognitive Impairment; Alzheimer Dementia; Reverse Transcriptase Inhibitors; Descovy; Emtricitabine; Alzheimer' s Disease