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

Condition(s) studied

Investigational drug(s) / intervention(s)

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

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

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

Placebo Capsules to Match Emtricitabine Capsules, 200mg.: White Opaque Body/Light Blue Opaque Cap with "GILEAD" and Gilead logo on body, "200 mg" on cap printed in black.

Study 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.

Eligibility

Primary outcome measure(s)

• Number of participants with treatment-related Adverse/Serious Adverse Events (AE/SAE) — From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).
  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.

Trial sites (1)

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