Clinical trial NCT04552795: Pilot Study to Investigate the Safety and Feasibility of AntiRetroviral Therapy for Alzheimer's Disease
Official title: Pilot Study to Investigate the Safety and Feasibility of AntiRetroviral Therapy for Alzheimer's Disease (ART-AD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Alzheimer Disease, Early Onset
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: Owens Medical Research Foundation
First posted: 2020-09-17
Enrollment: 12
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, one arm study.
Primary purpose: TREATMENT

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.

Detailed description: This open label study of 3TC will collect initial proof-of-concept data on 3TC target engagement, CNS penetration, efficacy and safety in older adults with early stage Alzheimer's disease. If successful, data will be used to design a larger phase 2 clinical trial. The investigators aim to I) Quantify 3TC target engagement and CNS penetration, II) Determine if 3TC suppresses Alzheimer's disease-relevant outcomes, and III) Assess the safety and tolerability of 3TC in older individuals with early Alzheimer's disease. The study will consist of a screening/baseline period of 30 days pre-treatment, a 24-week open label treatment period, and a follow up visit one month following treatment. Visits to the clinic include a pre-treatment screening visit that includes a comprehensive neuropsychological exam, a tablet-based neuropsychological exam, and a blood draw. For eligible participants, a lumbar puncture will be performed on day one of treatment. Participants will visit the clinic on day one of treatment and at weeks 8, 16, and 24 of treatment to complete medication checks, physical examinations, tablet-based cognitive screening, and blood draw. At week 24 of treatment, patients will undergo a post-treatment comprehensive neuropsychological exam, a lumbar puncture to collect cerebrospinal fluid, and a blood draw. One month after the final dose of medication, participants will return to the clinic for a final safety assessment and disenrollment.

Eligibility criteria: Inclusion Criteria:

1. Aged 50-99 years
2. Clinical diagnosis of early Alzheimer's disease (Clinical Dementia Rating (CDR) = 0.5, Mini-Mental State Exam (MMSE) = 24-30)
3. 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
4. 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
5. Body mass index (BMI) within range of 19 - 35 kg/m2
6. Must have a reliable informant or caregiver
7. Participants must have no plans to travel that interfere with study visits

Exclusion Criteria:

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

Primary outcomes:
measure: Change in Reverse Transcriptase Activity From Baseline to 24 Weeks in Plasma of Study Participants
timeFrame: Baseline to 24 weeks
measure: 3TC CNS Penetration
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in Dementia Severity From Baseline to Week 24 of Treatment Based on the PACC-5 Z-score
timeFrame: Baseline to 24 weeks
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Baseline to Week 24
measure: Incidence of Treatment-Emergent Abnormal Vital Signs
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases
state: Texas
city: San Antonio
country: United States
facility: Sam and Ann Barshop Institute for Longevity & Aging Studies
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: Univ of Texas Health Science Center at San Antonio
name: Bess Frost, PhD
role: PRINCIPAL_INVESTIGATOR
References: