Pilot Study to Investigate the Safety and Feasibility of AntiRetroviral Therapy for Alzheimer's Disease

NCT04552795 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HSC20200396H
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

The objective of the study is to evaluate the ability of (-)-L-2',3'-dideoxy-3'-thiacytidine (3TC) to engage its intended target, penetrate the central nervous system (CNS), suppress neurodegeneration, and assess safety and tolerability in patients with early stage Alzheimer's disease. This study will provide the initial data on target engagement and Alzheimer's disease-relevant outcomes for future trials.

Conditions

Alzheimer Disease, Early Onset

Outcome Measures

Primary Outcomes (2)

• Change in Reverse Transcriptase Activity From Baseline to 24 Weeks in Plasma of Study Participants

  The extent of 3TC target engagement was measured by calculating the change in reverse transcriptase activity in plasma of participants at baseline compared to week 24 using a modified version of the EnzCheck Reverse Transcriptase (RT) Assay.

  Baseline to 24 weeks

• 3TC CNS Penetration

  CNS penetration was calculated based on the ratio of CSF to plasma levels of 3TC after 24 weeks of 3TC using High Performance Liquid Chromatography with tandem Mass Spectrometry (HPLC/MS/MS).

  24 weeks

Secondary Outcomes (3)

• Change in Dementia Severity From Baseline to Week 24 of Treatment Based on the PACC-5 Z-score

  Baseline to 24 weeks

• Incidence of Treatment-Emergent Adverse Events

  Baseline to Week 24

• Incidence of Treatment-Emergent Abnormal Vital Signs

  Baseline to Week 24

Study Arms (1)

Open-Label 3TC

EXPERIMENTAL

12 subjects will receive 3TC, 300-mg, daily for 24 weeks.

Drug: 3TC

Interventions

3TC DRUG

12 subjects will be administered 3TC, 300mg once daily, via an oral tablet for 24 weeks.

Also known as: Epivir, lamivudine

Open-Label 3TC

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 50-99 years
• Clinical diagnosis of early Alzheimer's disease (Clinical Dementia Rating (CDR) = 0.5, Mini-Mental State Exam (MMSE) = 24-30)
• If using drugs to treat symptoms related to Alzheimer's disease, doses must be stable for at least eight weeks prior to screening visit 1
• Labs: Adequate blood cell counts (white blood cells: 4,000-111,000 cells per microliter (cells/mcL); absolute neutrophil count: 1,800-8,700 cells/mcL; platelets: 120-500 K/µL; hemoglobin 12.0-17.5 grams/dL); LFT's within 2x normal value; creatinine clearance test (CrCl) ≥ 50 mL/min; cholesterol (≤260 mg/dl), triglycerides≤ 400 mg/dl), and glucose control (HbA1c ≤ 8%). Prothrombin time/partial thromboplastin time/international normalized ratio (PT/PTT/INR) within normal limits
• Body mass index (BMI) within range of 19 - 35 kg/m2
• Must have a reliable informant or caregiver
• Participants must have no plans to travel that interfere with study visits

You may not qualify if:

• Any medical or neurologic condition (other than Alzheimer's Disease) that might be a contributing cause of the subject's cognitive impairment
• Clinically significant unstable psychiatric illness in the past six months
• Significant hearing, vision, or motor deficits that interfere with participation
• Alcohol or drug abuse/dependence in the past six months
• Stroke, transient ischemic attack, or unexplained loss of consciousness in the past six months
• Unstable angina, myocardial infarction, advanced chronic heart failure, or clinically significant conduction abnormalities within the past six months
• Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
• Diagnosis of HIV infection or AIDS (CD4 count \< 200), HIV/Hepatitis B Virus (HBV) co-infection, HBV or human T-cell leukemia virus infection
• History of impaired renal or liver function
• Current use of memantine or sorbitol-containing products
• Individuals with HIV, HBV, or who have current/previous use of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) or non-NRTIs.
• Poorly controlled blood pressure (BP) (systolic BP \> 160, diastolic BP \> 90 mmHg)
• Uncontrolled diabetes (HbA1c \> 8%, or the current use of insulin)
• Significant systematic illness or infection in the past 30 days
• Pregnant women

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• Owens Medical Research Foundation: collaborator

Study Sites (3)

Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases

San Antonio, Texas, 78229, United States

Location

Sam and Ann Barshop Institute for Longevity & Aging Studies

San Antonio, Texas, 78229, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Lamivudine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Bess Frost, PhD
• Organization: UT Health San Antonio

bfrost@uthscsa.edu

210-562-5037

Study Officials

• Bess Frost, PhD

  Univ of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Sam and Ann Barshop Instititute for Aging and Longevity Studies, Glenn Biggs Institute for Alzheimer's and Neurodegenerative Disorders, Department of Cell Systems and Anatomy

Model Details: Open-label, one arm study.

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: September 17, 2020
• Study Start: February 15, 2021
• Primary Completion: May 4, 2023
• Study Completion: November 4, 2023
• Last Updated: August 9, 2024
• Results First Posted: August 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After study completion, upon publication of data and on ClinicalTrials.gov 1 year after primary completion date of study.
• Access Criteria: Data will be analyzed by the study investigators.

Locations

US (3)