RECRUITING

Repurposing Nucleoside Reverse Transcriptase Inhibitors for Treatment of AD

Conditions

Alzheimer Disease, Early Onset Mild Cognitive Impairment Moderate Dementia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Repurposing Nucleoside Reverse Transcriptase Inhibitors for Treatment of AD

Quick Facts

Study Start:2021-12-17

Study Completion:2025-03-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04500847

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:50 Years to 85 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

Meghan Riddle, MD

CONTACT

(401) 455-6403

MRiddle@butler.org

Joslynn Faustino, PhD

CONTACT

(401) 455-6403

JFaustino@butler.org

Principal Investigator

Meghan Riddle, MD

PRINCIPAL_INVESTIGATOR

Butler Hospital

John Sedivy, PhD

PRINCIPAL_INVESTIGATOR

Brown University

Study Locations (Sites)

Memory and Aging Program, Butler Hospital

Providence, Rhode Island, 02906

United States

Collaborators and Investigators

Sponsor: Butler Hospital

Meghan Riddle, MD, PRINCIPAL_INVESTIGATOR, Butler Hospital
John Sedivy, PhD, PRINCIPAL_INVESTIGATOR, Brown University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-12-17

Study Completion Date2025-03-31

Study Record Updates

Study Start Date2021-12-17

Study Completion Date2025-03-31

Terms related to this study

Additional Relevant MeSH Terms

Alzheimer Disease, Early Onset
Mild Cognitive Impairment
Moderate Dementia