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.
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-tau217. 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 1.
Mini-Mental State Exam (MMSE) score of 18 to 30 (inclusive).
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.
Parallel
Emtricitabine and tenofovir disoproxil fumarate combination
DrugFTC 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.
Placebo
DrugPlacebo tablets.
Safety and tolerability
Treatment-emergent adverse events (AEs).
Safety and tolerability
Treatment-emergent serious AEs (SAEs)
Safety and tolerability
Changes in clinical laboratory tests. Specifically, will report the number of participants with abnormal laboratory values and/or AEs that are related to treatment.
Safety and tolerability
Changes in blood pressure (systolic and diastolic)
Pharmacokinetics (PK) Concentration average
PK of two ascending dose regimens of FTC-TDF combination: circulating drug levels pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours on Days 0 and 28; single nadir blood samples on days 3, 7, and 14 approximately 24 hours following the previous dose; single and multiple dose PK parameters calculated using nonparametric methods on days 0 and 28 (Concentration average 0-24 hours)
Pharmacodynamics (PD)
PD endpoint: steady-state serum concentration of active metabolites (TBP and ETP) in PBMCs pre-dose and at 4 and 8 hours after administration of study drug on days 0 and 28.
Activity of reverse transcriptase
LINE-1 in PBMCs on days 0 and 28.
Markers of systemic inflammation
hsCRP, IL-6, and TNF alpha on days 0, 14, and 28.
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This trial is not recruiting at the moment. You can still explore other options: