Repurposing Nucleoside Reverse Transcriptase Inhibitors for Treatment of AD

NCT04500847 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LINE-AD
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Alzheimer Disease, Early Onset; Mild Cognitive Impairment; Moderate Dementia

Outcome Measures

Primary Outcomes (1)

• Number 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).

  Baseline to the follow up study visit (7-8 months after first treatment)

Secondary Outcomes (7)

• Change from baseline in key inflammatory biomarkers; Tumor necrosis factor-alpha (TNF-α), Interleukin 1-beta (IL-1β), and Interferon-alpha (IFN-α)

  Baseline to the follow up study visit (7-8 months after first treatment)

• Change in Mini Mental State Examination (MMSE) Total Scores

  Screening phase, month 3 and month 6 after first treatment

• Change from baseline in Clinical Dementia Rating (CDR)

  Screening phase, month 3 and 6 months after first treatment

• Change from baseline in Alzheimer's Disease Assessment Scale-cognitive (ADAS-Cog -13)

  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)

  Screening phase, month 3 and month 6 after first treatment

Study Arms (2)

Group 1

ACTIVE COMPARATOR

25 MCI and mild to moderate AD subjects

Drug: Emtriva Capsule

Group 2

PLACEBO COMPARATOR

10 MCI and mild to moderate AD subjects

Drug: Placebo

Interventions

Emtriva Capsule DRUG

200mg daily oral dose

Also known as: Emtricitabine

Group 1

Placebo DRUG

200mg daily oral dose

Also known as: Capsule manufactured to mimic Emtriva

Group 2

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Butler Hospital: lead
• Alzheimer's Association: collaborator
• Brown University: collaborator
• The Miriam Hospital: collaborator
• Cedars Sinai Medical Center, Los Angeles, USA: collaborator

Study Sites (2)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Memory and Aging Program, Butler Hospital

Providence, Rhode Island, 02906, United States

RECRUITING

Related Publications (1)

• Ramirez P, Zuniga G, Sun W, Beckmann A, Ochoa E, DeVos SL, Hyman B, Chiu G, Roy ER, Cao W, Orr M, Buggia-Prevot V, Ray WJ, Frost B. Pathogenic tau accelerates aging-associated activation of transposable elements in the mouse central nervous system. Prog Neurobiol. 2022 Jan;208:102181. doi: 10.1016/j.pneurobio.2021.102181. Epub 2021 Oct 17.

  PMID: 34670118 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Emtricitabine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Meghan Riddle, MD

  Butler Hospital

  PRINCIPAL INVESTIGATOR

• John Sedivy, PhD

  Brown University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meghan Riddle, MD

CONTACT

(401) 455-6403; MRiddle@butler.org

Joslynn Faustino, PhD

CONTACT

(401) 455-6403; JFaustino@butler.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The pharmacist will not be masked. All investigators will be masked until the end of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Neurology and the Memory and Aging Program

Study Record Dates

• First Submitted: June 15, 2020
• First Posted: August 5, 2020
• Study Start: December 17, 2021
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: May 4, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)