Safety Of Nrtis for Alzheimer's Therapeutic Advancement in Singapore Study

NCT07210528 | Recruiting Phase 1

• 1 other identifier: RTi-EmtriDes-2022
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Recent studies have identified an association between Alzheimer's Disease (AD) and an expansion of DNA content in the brain (prefrontal cortex). This additional DNA content appears to be derived from reverse transcriptase (RT) activity that incorporates genomic cDNAs (gencDNAs) into chromosomes, resulting in multiple copies of full length and shorter cDNAs involving many genes - including the causal AD gene amyloid precursor protein (APP). Accumulation of these APP gencDNAs is associated with AD. This identifies RT as a promising therapeutic target for the attenuation of AD progression through existing reverse transcriptase inhibitors (RTi's) that have been widely used for treating HIV and hepatitis B. Since this class of drugs has been in the clinic for over 3 decades, there are significant data supporting their post-approval safety for long-term use. However, this has not been specifically addressed in the target population - patients with mild cognitive impairment (MCI), particularly women - who are underrepresented in HIV datasets. This proposed Phase I safety trial will perform a Special Population Study in a cohort of MCI patients who may benefit from the intervention. This study aims to (1) evaluate the safety and tolerability of standard dose FTC or Descovy for 3 months in MCI patients; (2) as secondary aims, collect preliminary data on clinical effects of standard dose FTC or Descovy compared to placebo for 3 months on cogntiive function in MCI patients; and (3) collect preliminary data on clinical effects of standard dose FTC or Descovy compared with placebo on AD-associated inflammatory markers. Participants will be randomized into either Descovy or FTC arms in equal numbers, and receive either active drug or placebo. Participants will orally ingest 1 capsule or tablet (depending on drug arm) daily for the 3 month participation period. The investigators hypothesise that MCI are not at increased risk of adverse effects due to administration of standard dose FTC or Descovy.

Conditions

Mild Cognitive Impairment (MCI); Alzheimer Dementia (AD)

Keywords

Reverse Transcriptase Inhibitors; Mild Cognitive Impairment (MCI); Descovy; Emtricitabine; Alzheimer's Disease (AD)

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related Adverse/Serious Adverse Events (AE/SAE)

  Number of participants with treatment-related AE/SAEs as assessed on the CTCAE Version 4.0. Incidence rate (n = x, and %), cause, and type of AE/SAE will be compared across the active drug and placebo groups.

  From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).

Secondary Outcomes (10)

• Change in circulating Beta-Amyloid 40 (Aβ40), Beta-Amyloid 42 (Aβ42) and Aβ-40: Aβ-42 ratio from baseline.

  From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).

• Change in Phospho-Tau217 (Ptau217) from baseline.

  From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).

• Change in Interleukin-6 (IL-6) levels from baseline.

  From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).

• Change in Interleukin-8 (IL-8) levels from baseline.

  From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).

• Change in Tumor Necrosis Factor-alpha (TNFα) levels from baseline.

  From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).

Study Arms (4)

Descovy

EXPERIMENTAL

Equal numbers of male and female participants will be recruited in all arms. Descovy, Tablet, 200/25 mg, ct, Bottle, Britestock.

Drug: Descovy® (TAF/FTC)

Placebo to Match Descovy

PLACEBO COMPARATOR

Equal numbers of male and female participants will be recruited in all arms. Placebo to match Descovy. Tablets, Rectangular-Shaped, Debossed, Film-Coated Blue, 30ct per bottle.

Drug: Placebo to Match Emtricitabine 200mg/Tenofovir Alafenamide 25 mg.

Emtricitabine (Emtriva)

EXPERIMENTAL

Equal numbers of male and female participants will be recruited in all arms. Emtriva, Capsule, 200 mg, 30 ct, Bottle, Britestock.

Drug: Emtricitabine (FTC)

Placebo to match Emtricitabine (Emtriva)

PLACEBO COMPARATOR

Equal numbers of male and female participants will be recruited in all arms. Placebo Capsules to Match Emtricitabine Capsules, 200 mg, White Opaque Body/Light Blue Opaque Cap with "GILEAD" and Gilead Logo on body, "200 mg" on cap printed in black, 30 ct per bottle.

Drug: Placebo Capsules to Match Emtricitabine Capsules, 200mg.

Interventions

Emtricitabine (FTC) DRUG

Capsule, 200mg FTC. White Opaque Body / Light Blue Opaque Cap with "GILEAD" and Gilead logo on body. "200 mg" on cap printed in black.

Also known as: Emtriva

Emtricitabine (Emtriva)

Descovy® (TAF/FTC) DRUG

Emtricitabine (FTC) 200 mg / Tenofovir Alafenamide (TAF) 25 mg. Tablets, Rectangular-Shaped, Debossed, Film-coated blue.

Descovy

Placebo to Match Emtricitabine 200mg/Tenofovir Alafenamide 25 mg. DRUG

Placebo to Match Emtricitabine 200mg/Tenofovir Alafenamide 25mg. Tablets, Rectangular-Shaped, Debossed, Film-Coated Blue.

Placebo to Match Descovy

Placebo Capsules to Match Emtricitabine Capsules, 200mg. DRUG

White Opaque Body/Light Blue Opaque Cap with "GILEAD" and Gilead logo on body, "200 mg" on cap printed in black.

Placebo to match Emtricitabine (Emtriva)

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

Emtricitabine; Racivir; emtricitabine tenofovir alafenamide; tenofovir alafenamide

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Christopher Chen

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jit Hui Mark Lim

CONTACT

+65 98376041; mjhl@nus.edu.sg

Veronica Ho

CONTACT

+65 8810 9782; veronica_ho@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: October 7, 2025
• Study Start: June 30, 2025
• Primary Completion: March 1, 2026
• Study Completion: April 1, 2026
• Last Updated: October 7, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)