This is a randomized, double-blind clinical trial of a daily oral dose of 200 mg emtricitabine vs. placebo in 35 participants with biomarker-confirmed MCI or mild to moderate dementia due to Alzheimer's disease. Study duration for each subject participating in the placebo-controlled research study will be approximately 12 months (up to a 3 months Screening Period, Baseline visit (1 month), 6 months of placebo or emtricitabine dosing, and 1 month follow-up). Participants will have up to 2 months to complete all procedures for the month 6 study visit.
Alzheimer's disease (AD) is a devastating and increasingly frequent neurological disorder whose onset is strongly correlated with advanced age. Between 2000 and 2017 deaths from AD have increased 145%, and AD has become the 6th leading cause of death in the USA. Unfortunately, in spite of immense research and clinical efforts spanning several decades, cures have been elusive. This has prompted searches for new mechanisms of disease and new targets of therapy. One such direction is inflammation: aging and many age-associated diseases are believed to be causally linked with a chronic inflammatory state. The brain is no exception, and the presence of inflammation in the AD brain establishes an environment that is hostile for the function and survival of neurons. While it is not yet clear whether inflammation is the root cause of AD, it is increasingly believed that alleviating these inflammatory processes might slow down the progression of the disease. This research study will test to determine if the inflammatory state can be alleviated with a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs were developed to treat Acquired Immune Deficiency Syndrome (AIDS) caused by infection with Human Immunodeficiency Virus (HIV). Investigators hypothesize that NRTI drugs, by inhibiting neuroinflammation, may be effective in the treatment of AD. The primary goal of this trial will be to assess safety and tolerability of Emtriva in a geriatric population of individuals diagnosed with mild cognitive impairment or early AD. This study will be conducted in subjects with mild to moderate Alzheimer's disease (AD), including subjects with mild cognitive impairment (MCI). Subjects must be positive for amyloid pathology. Subjects must be 50 to 85 years old, and apart from the clinical diagnosis of early AD, in good health as determined by the Investigator based on their medical history. Participants must be HIV/HBV negative and pass all the screening assessments based on the inclusion/exclusion criteria.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
35
200mg daily oral dose
200mg daily oral dose
Cedars-Sinai Medical Center
Los Angeles, California, United States
RECRUITINGMemory and Aging Program, Butler Hospital
Providence, Rhode Island, United States
RECRUITINGNumber of participants with treatment emergent adverse events (TEAE's) in the treatment group will be compared to the placebo group
Number of participants with treatment emergent adverse events and serious adverse events as assessed by CTCAE (Version 4.03).
Time frame: Baseline to the follow up study visit (7-8 months after first treatment)
Change from baseline in key inflammatory biomarkers; Tumor necrosis factor-alpha (TNF-α), Interleukin 1-beta (IL-1β), and Interferon-alpha (IFN-α)
Blood draws will be taken from baseline to the follow up study visit. Inflammation and discovery research assays to detect levels of TNF-α, IL-1β, and IFN-α will be performed at Brown University.
Time frame: Baseline to the follow up study visit (7-8 months after first treatment)
Change in Mini Mental State Examination (MMSE) Total Scores
To determine changes of the MMSE scores from the screening phase to 6 months after first treatment.
Time frame: Screening phase, month 3 and month 6 after first treatment
Change from baseline in Clinical Dementia Rating (CDR)
To determine changes of CDR scores from screening phase to 6 months after first treatment.
Time frame: Screening phase, month 3 and 6 months after first treatment
Change from baseline in Alzheimer's Disease Assessment Scale-cognitive (ADAS-Cog -13)
To determine changes in ADAS-Cog scores from screening phase to 6 months after first treatment.
Time frame: Screening phase, month 3 and month 6 after first treatment
Change from baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
To determine changes in ADCS-ADL scores from screening phase to 6 months after first treatment.
Time frame: Screening phase, month 3 and month 6 after first treatment
Change from baseline in Free and Cued Selective Reminding Test (FCSRT+IR) with delayed recall
To determine changes in FCSRT+IR with delayed recall from screening phase to 6 months after first treatment.
Time frame: Screening phase, month 3 and month 6 after first treatment
Change from baseline in cerebrospinal fluid (CSF) phosphorylated tau/amyloid beta 42 (pTau/Aβ42) ratios
To determine changes in pTau/Aβ42 ratios from the screening phase to 6 months after first treatment.
Time frame: Screening phase to month 6-7 after first treatment
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