Repurposing Nucleoside Reverse Transcriptase Inhibitors for Treatment of AD (LINE-AD)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04500847|
Recruitment Status : Recruiting
First Posted : August 5, 2020
Last Update Posted : December 22, 2021
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease, Early Onset Mild Cognitive Impairment||Drug: Emtriva Capsule Drug: Placebo||Phase 1|
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 early Alzheimer's disease (AD), including subjects with mild cognitive impairment (MCI) due to AD. 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 (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||The pharmacist will not be masked. All investigators will be masked until the end of the study.|
|Official Title:||Repurposing Nucleoside Reverse Transcriptase Inhibitors for Treatment of AD|
|Actual Study Start Date :||December 17, 2021|
|Estimated Primary Completion Date :||March 31, 2023|
|Estimated Study Completion Date :||August 2023|
Active Comparator: Group 1
25 MCI and early AD subjects
Drug: Emtriva Capsule
200mg daily oral dose
Other Name: Emtricitabine
Placebo Comparator: Group 2
10 MCI and early AD subjects
200mg daily oral dose
Other Name: Capsule manufactured to mimic Emtriva
- Number of participants with treatment emergent adverse events (TEAE's) in the treatment group will be compared to the placebo group [ Time Frame: Baseline to the follow up study visit (7 months after first treatment) ]Number of participants with treatment emergent adverse events and serious adverse events as assessed by CTCAE (Version 4.03).
- Change from baseline in key inflammatory biomarkers; Tumor necrosis factor-alpha (TNF-α), Interleukin 1-beta (IL-1β), and Interferon-alpha (IFN-α) [ Time Frame: Baseline to the follow up study visit (7 months after first treatment) ]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.
- Change in Mini Mental State Examination (MMSE) Total Scores [ Time Frame: Screening phase, month 3 and month 6 after first treatment ]To determine changes of the MMSE scores from the screening phase to 6 months after first treatment.
- Change from baseline in Clinical Dementia Rating (CDR) [ Time Frame: Screening phase, month 3 and 6 months after first treatment ]To determine changes of CDR scores from screening phase to 6 months after first treatment.
- Change from baseline in Alzheimer's Disease Assessment Scale-cognitive (ADAS-Cog -13) [ Time Frame: Screening phase, month 3 and month 6 after first treatment ]To determine changes in ADAS-Cog scores from screening phase to 6 months after first treatment.
- Change from baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) [ Time Frame: Screening phase, month 3 and month 6 after first treatment ]To determine changes in ADCS-ADL scores from screening phase to 6 months after first treatment.
- Change from baseline in Free and Cued Selective Reminding Test (FCSRT+IR) with delayed recall [ Time Frame: Screening phase, month 3 and month 6 after first treatment ]To determine changes in FCSRT+IR with delayed recall from screening phase to 6 months after first treatment.
- Change from baseline in cerebrospinal fluid (CSF) phosphorylated tau/amyloid beta 42 (pTau/Aβ42) ratios [ Time Frame: Screening phase to month 6 after first treatment ]To determine changes in pTau/Aβ42 ratios from the screening phase to 6 months after first treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04500847
|Contact: Stephen Salloway, MD||(401) 455-6403||SSalloway@butler.org|
|Contact: Joslynn Faustino, PhD||(401) 455-6403||JFaustino@butler.org|
|Principal Investigator:||Stephen Salloway, MD||Butler Hospital|
|Principal Investigator:||John Sedivy, PhD||Brown University|