Repurposing Nucleoside Reverse Transcriptase Inhibitors for Treatment of Alzheimer's Disease

What is the Purpose of this Study?

The purpose of this study is to determine whether a medication called emtricitabine is safe and tolerable in people with mild to moderate Alzheimer’s disease (AD). Researchers also want to learn whether emtricitabine has the potential to be a helpful treatment that slows down disease progression compared to placebo (inactive substance). The study aims to explore a new direction for potential AD treatment that focuses on neuro-inflammation (inflammation in the brain). Neuro-inflammation is believed to contribute to AD; therefore, alleviating neuro-inflammation may slow down AD progression. Emtricitabine, which stops HIV from replicating, may also stop DNA from making copies and potentially stop the immune system from causing inflammation in the brain. The use of emtricitabine in this study is investigational.

Eligibility

* 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

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.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

LINE AD: Repurposing nucleoside reverse transcriptase inhibitors for treatment of AD

Study Details

Disease Type/Condition

Other

Principal Investigator

Espinoza, Sara

Age Group

Adult

Phase

III

IRB Number

STUDY00003008

ClinicalTrials.gov ID

NCT04500847

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org