Repurposing a Combination Antiretroviral Drug Therapy to Target Retrotransposons and Treat Early Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Safety and tolerability
研究概览
简要总结
The goal of this clinical trial is to determine the safety, tolerability, drug levels and biological effects of two doses of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) combination administered daily for 4 weeks in older adults with early Alzheimer's disease. The main questions it aims to answer are:
- Is FTC-TDF combination safe in older adults who have early Alzheimer's disease.
- To measure the FTC-TDF levels at different times.
- To measure the biological effects of FTC-TDF combination.
- To measure the effects of FTC-TDF combination on inflammation.
Researchers will compare two doses of FTC-TDF combination to a placebo (a look-alike substance that contains no drug) to see if FTC-TDF combination is safe in older adults who have early Alzheimer's disease.
Participants will:
- Take FTC-TDF combination or a placebo every day for 28 days.
- Have 10 clinic visits over approximately 3 months.
- Undergo blood tests, physical exams, cognitive testing, and scans of their brain.
详细描述
Objectives:
To conduct a phase 1b trial to determine the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple ascending doses of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) combination administered daily for 4 weeks in older adults with early Alzheimer's disease (AD).
Primary:
1) To evaluate safety and tolerability, we will conduct structured monitoring of adverse events (AEs) and serious AEs (SAEs). Additionally, we will perform safety laboratory tests including blood counts and chemistries, coagulation profile, physical exams, vital signs, and electrocardiogram (ECG).
Secondary:
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Study coordinators, cognitive raters, nurses, MRI technicians, lab technicians.
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets National Institute on Aging-Alzheimer's Association clinical diagnostic criteria for mild cognitive impairment (MCI) or AD dementia.
- •Has evidence of AD assessed by plasma p-tau
- •Prior cerebrospinal fluid (CSF) or positron emission tomography (PET) amyloid testing (obtained clinically or through previous research) from the past 2 years may be used for eligibility with approval from study investigators.
- •Clinical Dementia Rating (CDR) global score of 0.5 or
- •Mini-Mental State Exam (MMSE) score of 18 to 30 (inclusive).
- •15-item Geriatric Depression Scale (GDS) score of <
- •Impaired memory performance below an education adjusted cut-off score on the Logical Memory II subscale delayed paragraph recall of Wechsler Memory Scale-Revised (WMS-R) (≥16 years: ≤8; 8-15 years: ≤4; 0-7 years: ≤2).
- •May take FDA approved medications for the treatment of AD dementia, but if taking such medications, they must be stable for at least 8 weeks before screening (for cholinesterase inhibitors and/or memantine) or 6 months (for lecanemab or donanemab).
- •Has adequate visual and auditory acuity to participate in neuropsychological testing and other study outcomes.
- •Has availability of a study partner who has regular contact with the participant and knows him/her well.
- •Is willing and able to participate in all assessments in English.
- •Is capable of providing written informed consent
排除标准
- •Neurologic diseases: Neurologic disease other than AD such as Parkinson's disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia, normal pressure hydrocephalus, corticobasal syndrome, malignant brain tumor (within the last 1 year), multiple sclerosis, or significant head trauma (e.g. with loss of consciousness for 30 minutes or more) followed by persistent neurologic deficits, or significant structural brain abnormalities.
- •Neuroimaging: Magnetic resonance imaging (MRI) scan evidence of cortical stroke or macrohemorrhage (>1 cm), strategically located lacunar stroke, or severe small vessel disease.
- •Alcohol or substance use disorder or dependence (Diagnostic and Statistical Manual of Mental Disorders version 5 [DSM 5] criteria) within the last 2 years.
- •Untreated major depressive disorder (within the last 1 year), bipolar disorder, schizophrenia (DSM 5 criteria), or current major psychotic symptoms or behavioral problems.
- •Any systemic illness or unstable medical conditions, which could affect valid cognitive and self-report assessments.
- •Excluded medications: Antipsychotic medications; antidepressant medications with anticholinergic side effects. Washout from psychoactive medications for at least 8 weeks before screening.
- •Laboratory abnormalities: AST or ALT > 3 times the upper limit of normal; creatinine clearance <60 mL/min; HbA1C > 8.5%.
- •Participation in an investigational trial within the past 3 months or 5 half-lives, whichever is shorter
- •Conditions which, in the opinion of the investigator, would jeopardize safety or impact the validity of the study results.
- •Person who is positive for HBV Surface Antigen.
- •Person with a history of osteoporosis or osteomalacia.
- •Person taking FTC-TDF for pre-exposure prophylaxis or treatment of HIV.
研究组 & 干预措施
FTC and TDF combination tablet
FTC and TDF combination tablets at two dose strengths that are in clinical use: 133 mg FTC plus 200 mg TDF, and 200 mg FTC plus 300 mg TDF. There is a 70% chance participants will receive the FTC-TDF combination.
干预措施: Emtricitabine and tenofovir disoproxil fumarate combination (Drug)
Placebo
Placebo tablets. There is a 30% chance participants will receive placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and tolerability
时间窗: 28 days
Treatment-emergent adverse events (AEs).
次要结局
- Pharmacokinetics (PK) Concentration average(28 days)
- Pharmacodynamics (PD)(28 days)
- Activity of reverse transcriptase(28 days)
- Markers of systemic inflammation(28 days)
- Pharmacokinetics (PK) Concentration maximum(28 days)
- Pharmacokinetics (PK) T max(28 days)
- Pharmacokinetics (PK) lambda z(28 days)
- Pharmacokinetics (PK) AUC last(28 days)
- Pharmacokinetics (PK) AUC 24 hours(28 days)
- Pharmacokinetics (PK) T 1/2(28 days)
研究者
Gad A. Marshall, MD
Professor of Neurology
Brigham and Women's Hospital