A Phase 1b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of Emtricitabine and Descovy in Patients With Mild Cognitive Impairment.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related Adverse/Serious Adverse Events (AE/SAE)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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; OR presenting with SCD and a CDR-GS of 0.
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo to match Emtricitabine (Emtriva)
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.
干预措施: Placebo Capsules to Match Emtricitabine Capsules, 200mg. (Drug)
Descovy
Equal numbers of male and female participants will be recruited in all arms. Descovy, Tablet, 200/25 mg, ct, Bottle, Britestock.
干预措施: Descovy® (TAF/FTC) (Drug)
Emtricitabine (Emtriva)
Equal numbers of male and female participants will be recruited in all arms. Emtriva, Capsule, 200 mg, 30 ct, Bottle, Britestock.
干预措施: Emtricitabine (FTC) (Drug)
Placebo to Match Descovy
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.
干预措施: Placebo to Match Emtricitabine 200mg/Tenofovir Alafenamide 25 mg. (Drug)
结局指标
主要结局
Number of participants with treatment-related Adverse/Serious Adverse Events (AE/SAE)
时间窗: 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.
次要结局
- 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).)
- Change in Mini Mental State Exam scores (MMSE).(From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).)
- Change in Quick Dementia Rating Scores (QDRS) from baseline.(From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).)
- Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores from baseline.(From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).)
- Change in Colour Trials Test (CTT) scores from baseline.(From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).)
- Change in Activities of Daily Living (ADL) scores from baseline.(From enrollment to the end of treatment at 12 weeks (measured from participant's baseline visit).)