Repurposing Nucleoside Reverse Transcriptase Inhibitors for Treatment of AD (LINE-AD)

May 1, 2025 updated by: Meghan Riddle, Butler Hospital
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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 mild to moderate Alzheimer's disease (AD), including subjects with mild cognitive impairment (MCI). 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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
35

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
        • Principal Investigator:
          • Sara Espinoza, MD
        • Contact:
        • Sub-Investigator:
          • Nicolas Musi, MD
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Recruiting
        • Memory and Aging Program, Butler Hospital
        • Contact:
        • Contact:

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

46 years to 81 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Group 1
25 MCI and mild to moderate AD subjects
Drug: Emtriva Capsule
200mg daily oral dose
Other Names:
  • Emtricitabine
Placebo Comparator: Group 2
10 MCI and mild to moderate AD subjects
Drug: Placebo
200mg daily oral dose
Other Names:
  • Capsule manufactured to mimic Emtriva

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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 (7-8 months after first treatment)
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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 (7-8 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.
Baseline to the follow up study visit (7-8 months after first treatment)
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.
Screening phase, month 3 and month 6 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.
Screening phase, month 3 and 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.
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)
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.
Screening phase, month 3 and month 6 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.
Screening phase, month 3 and month 6 after first treatment
Change from baseline in cerebrospinal fluid (CSF) phosphorylated tau/amyloid beta 42 (pTau/Aβ42) ratios
Time Frame: Screening phase to month 6-7 after first treatment
To determine changes in pTau/Aβ42 ratios from the screening phase to 6 months after first treatment.
Screening phase to month 6-7 after first treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Butler Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Brown University
The Miriam Hospital
Alzheimer's Association
Cedars Sinai Medical Center, Los Angeles, USA

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Meghan Riddle, MD, Butler Hospital
  • Principal Investigator: John Sedivy, PhD, Brown University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 17, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 15, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 5, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 4, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 1, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LINE-AD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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