Repurposing Nucleoside Reverse Transcriptase Inhibitors for Treatment of AD

Launched by BUTLER HOSPITAL · Aug 3, 2020

Keywords

ClinConnect Summary

This clinical trial is looking at a medication called emtricitabine to see if it can help people with early-stage Alzheimer’s disease or mild cognitive impairment. The study will involve 35 participants who will take either emtricitabine or a placebo (a pill that looks like the medication but has no active ingredients) for six months. Researchers want to find out if emtricitabine can improve memory and thinking skills in those affected by Alzheimer’s. The entire study will last about a year, including time for screening, check-ups, and follow-ups.

To be eligible, participants need to be between 50 and 85 years old and have certain cognitive test scores that indicate mild dementia or mild cognitive impairment. They also need to have a study partner who can help them throughout the trial. Participants should not have other serious medical or neurological conditions that could affect their thinking or memory. If you or someone you know is interested in this trial, it could be a chance to help advance research on Alzheimer’s disease while possibly receiving new treatment options.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Male or female, ages 50-85 years inclusive
• • Intellectually, visually and auditory capable, fluent in, and able to read, the language in which study assessments are administered (e.g. completion of at least six years of regular schooling or sustained employment or equivalent local level of knowledge).
• • Must meet NIA-AA research criteria for MCI and mild dementia due to AD
• • Mini Mental State Exam (MMSE) 15-30 inclusive
• • Clinical Dementia Rating (CDR) 0.5 - 2
• • Must meet a cerebrospinal fluid (CSF) pTau/Aβ42 ratio of \> 0.024
• • Participants must have an appropriate study partner who agrees to participate in the study and who is intellectually, visually, and auditory capable, and fluent in, and able to read, the language in which study assessments are administered. Additionally, the study partner must be capable of and willing to: Accompany the participant to visits that requires the input of the study partner
• • Concurrent treatment with cholinesterase inhibitors and memantine are permitted on a stable dose for at least 60 days prior to baseline.
• Exclusion Criteria:
• • Current medical or neurological condition that might impact cognition or performance on cognitive assessments, e.g., Huntington's disease, Parkinson's disease, syphilis, schizophrenia, bipolar disorder, active major depression, attention deficit/ hyperactivity disorder (ADD/ADHD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), active seizure disorder, current alcohol/drug abuse or dependence, or dependence within the last two years, or history of traumatic brain injury associated with loss of consciousness and ongoing residual transient or permanent neurological signs/symptoms including cognitive deficits, and/or associated with skull fracture
• • Brain MRI results showing findings unrelated to AD that, in the opinion of the investigator might be a leading cause of future cognitive decline, might pose a risk to the participant, or might confound MRI assessment for safety monitoring
• • Score "yes" on item four or item five of the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (eC-SSRS patient-reported outcome), if this ideation occurred in the past six months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item is included in the Suicidal Behavior section), if this behavior occurred in the past 2 years prior to screening
• * Use of other investigational drugs prior to screening until:
• • Small molecules: after five half-lives, or within 30 days until the expected pharmacodynamic effect has returned to baseline, whichever is longer
• • Biologicals: blood concentration has returned to baseline (or below serological responder threshold) for antibodies induced by active immunotherapy; or five half- lives for monoclonal antibodies or other biologicals
• • Approximately four weeks prior to randomization, the use of any drug or treatment known for the potential to cause major organ system toxicity, i.e. drugs that may require periodic safety monitoring of a specific organ or body fluid. Examples include, but are not limited to clozapine, cancer medical treatment like tamoxifen, systemic immunosuppressive drugs like methotrexate or interferon, or other immunosuppressive biological medicines for rheumatic diseases or multiple sclerosis
• • A positive drug screen, if, in the investigator's opinion, this is due to drug abuse or dependence.
• • Significant ECG findings that are assessed as clinically significant by the investigator (e.g. sustained ventricular tachycardia, significant second or third degree atrioventricular block without a pacemaker, long QT syndrome or clinically meaningful prolonged QT interval).
• • Contraindication to lumbar puncture including use of anti-coagulants, low platelet count, history of back surgery (with the exception of microdiscectomy or laminectomy over one level), signs or symptoms of intracranial pressure, spinal deformities or other spinal conditions that in the judgment of the investigator would preclude a lumbar puncture
• • History of or active hepatitis or HIV infection (based on a positive lab result for HBV and/or HIV, to be performed during screening
• • Severe renal impairment
• • Severe hepatic impairment
• • Significant cardiac disease including recent (within six months) myocardial infarction, congestive heart failure or unstable angina
• • Female subjects who are pregnant or currently breastfeeding.