Safety Of Nrtis for Alzheimer's Therapeutic Advancement in Singapore Study
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age50-85
SponsorNational University Hospital, Singapore
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Emtricitabine (FTC)
DrugCapsule, 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)
DrugEmtricitabine (FTC) 200 mg / Tenofovir Alafenamide (TAF) 25 mg. Tablets, Rectangular-Shaped, Debossed, Film-coated blue.
Placebo to Match Emtricitabine 200mg/Tenofovir Alafenamide 25 mg.
DrugPlacebo to Match Emtricitabine 200mg/Tenofovir Alafenamide 25mg. Tablets, Rectangular-Shaped, Debossed, Film-Coated Blue.
Placebo Capsules to Match Emtricitabine Capsules, 200mg.
DrugWhite Opaque Body/Light Blue Opaque Cap with "GILEAD" and Gilead logo on body, "200 mg" on cap printed in black.
Treatment groups
48 Participants
are divided into 4 treatment groupsGroup A: DescovyExperimental treatment 1 intervention
Group B: Placebo to Match DescovyPlacebo comparator 1 intervention
Group C: Emtricitabine (Emtriva)Experimental treatment 1 intervention
Group D: Placebo to match Emtricitabine (Emtriva)Placebo comparator 1 intervention
Trial outcomes
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.
Time frame
From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).Secondary outcomes
1
Change in circulating Beta-Amyloid 40 (Aβ40), Beta-Amyloid 42 (Aβ42) and Aβ-40: Aβ-42 ratio from baseline.
Changes in plasma Aβ-40 and Aβ-42 levels; and Aβ40:Aβ42 ratio from baseline visit to week 12 visit, as assessed on Single Molecular Array (SIMOA). Units: pg/mL. No reference range is reported as significant variation exists across cohorts.
Time frame
From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).2
Change in Phospho-Tau217 (Ptau217) from baseline.
Change in total plasma Ptau217 levels from baseline visit to week 12 visit, as assessed on Single Molecular Array (SIMOA). Units: pg/mL. No reference range is reported as significant variation exists across cohorts.
Time frame
From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).3
Change in Interleukin-6 (IL-6) levels from baseline.
Change in serum IL-6 levels from baseline to week 12 visit, as assessed on Luminex Multiplex Analyser. Units: pg/mL. No reference range is reported as significant variation exists across cohorts.
Time frame
From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).4
Change in Interleukin-8 (IL-8) levels from baseline.
Change in serum IL-8 levels from baseline to week 12 visit, as assessed on Luminex Multiplex Analyser. Units: pg/mL. No reference range is reported as significant variation exists across cohorts.
Time frame
From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov