← Trials/Trial dossier/NCT04500847

LINE-AD

RecruitingPhase 1

Repurposing Nucleoside Reverse Transcriptase Inhibitors for Treatment of AD

Lead sponsor

Butler Hospital

Asset

Emtricitabine

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•Alzheimer's disease•MMSE 15-30•Study partner/caregiver required•AD symptomatic therapy: stable

Primary endpoint

•Treatment emergent adverse events (TEAE's) in the treatment group will be

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDLINE-AD

NCT IDNCT04500847

Timeline

Milestones

Study first posted2020-08-05actual

Study start2021-12-17actual

Last update posted2025-05-04actual

Primary completion2026-03-31estimated

Study completion2026-03-31estimated

Assets

Drug assets

Emtricitabine

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

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.

Endpoints (8)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Memory

Function / daily living

Amyloid biomarkers

Safety / tolerability / PK

Other (unclassified)

Global cognition

3 endpoints

Secondary/protocol endpoint

Change in Mini Mental State Examination (MMSE) Total Scores

Time frame:Screening phase, month 3 and month 6 after first treatment

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Change from baseline in Clinical Dementia Rating (CDR)

Time frame:Screening phase, month 3 and 6 months after first treatment

change from baseline, improvement

Secondary/protocol endpoint

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

ADAS-Cog

change from baseline, improvement

Memory

1 endpoint

Secondary/protocol endpoint

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

change from baseline, improvement

Function / daily living

1 endpoint

Secondary/protocol endpoint

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

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Amyloid biomarkers

1 endpoint

Secondary/protocol endpoint

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

change from baseline, improvement

Safety / tolerability / PK

1 endpoint

Primary/protocol endpoint

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)

event count, event

Other (unclassified)

1 endpoint

Secondary/protocol endpoint/low confidence

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)

change from baseline, improvement

Publications (2)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.