Efavirenz for Patients With Alzheimer's Disease

NCT03706885 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ADDF 20160601
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a two-center, placebo controlled blinded clinical trial to evaluate the safety and tolerability of efavirenz (EFV) in 36 clinically stable subjects with mild cognitive impairment/early dementia due to Alzheimer's Disease (AD) age ≥55 years. Of these 36 total subjects, 18 will be recruited by MGH and 18 will be recruited by UH. A subset of the subjects at MGH only will also participate in a Stable Isotope Labeling Kinetics (SILK) protocol with deuterated water (a nonhazardous substance), designed to more precisely measure EFV effects on CNS cholesterol turnover. Each respective site's 18 total recruited individuals will be divided into 3 groups: these 3 groups will represent two particular dosages of EFV and a placebo group, respectively. In a double-blind fashion, participants will be receiving either a capsule of EFV or placebo daily for 20 weeks. At MGH only, 12 individuals (4 from each of the two EFV groups and placebo) will participate in the unique "heavy water" SILK protocol assessing the kinetics of deuterium enrichment in plasma 24-hydroxycholesterol (24-OHC). All study participants at both sites will have their blood, cerebral spinal fluid, and urine analyzed at various points throughout the study. All participants will have their DNA genotyped for APOE isoforms (E2, E3 or E4) and single nucleotide polymorphisms (SNPs) in CYP46A1 (rs754203) and CYP2B6 (rs3745274) to be used for post-hoc analysis.

Conditions

Alzheimer Disease, Early Onset

Outcome Measures

Primary Outcomes (1)

• Plasma levels of 24-hydroxycholesterol

  Changes in plasma 24-hydroxycholesterol (measured in ng/dL) by more or equal to 30%.

  1 year

Secondary Outcomes (2)

• Plasma levels of deuterated 24-hydroxycholesterol

  1 year

• APOE isoform status (E2, E3, or E4) and presence of the SNPs rs754203 and rs3745274 in CYP46A1 and CYP2B6, respectively.

  1 year

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Treatment with placebo - 1 pill per day for 20 weeks

Drug: Sustiva Pill

Sustiva 50mg

ACTIVE COMPARATOR

Treatment with Sustiva 50mg - 1 pill per day for 20 weeks

Drug: Sustiva Pill

Sustiva 200mg

ACTIVE COMPARATOR

Treatment with Sustiva 200mg - 1 pill per day for 20 weeks

Drug: Sustiva Pill

Interventions

Sustiva Pill DRUG

One pill (Sustiva 50 mg or Sustiva 200mg or Placebo) One pill per day for 20 weeks

Also known as: Efavirenz

Placebo; Sustiva 200mg; Sustiva 50mg

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between the ages of 55-85
• Either male or female
• Diagnosis of (a) as per below:
• a) Mild Cognitive Impairment (MCI) or early dementia due to AD as defined by (1) complaint of cognitive decline, (2) MMSE Total=16-30, (3) CDR=0.5-1
• Fluent in English
• Education \>8 years, literate, and/or good working history that precludes consideration of mental retardation
• Visual and auditory acuity sufficient for neuropsychological testing
• Modified Hachinski Ischemic Score\<4
• No major health issues or diseases expected to interfere with the study
• Willing to complete all assessments and study procedures
• Not pregnant, lactating or of child-bearing potential (women must be \>2 years post- menopausal or surgically sterile)
• If cognitively impaired, study partner with frequent contact with patient willing to accompany patient to visits and complete partner study forms
• No contraindication or hypersensitivity to EFV
• Screening laboratory testing must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigators
• Stable use of cholinesterase inhibitor is permitted if doses are stable for 3 months prior to enrollment

You may not qualify if:

• Any CNS disease other than suspected prodromal or early AD, such as clinical stroke, brain tumor, normal pressure hydrocephalus, brain tumor, multiple sclerosis, significant head trauma with persistent neurological or cognitive deficits or complaints, Parkinson's Disease, frontotemporal dementia, or other neurodegenerative diseases
• Ongoing major and active psychiatric disorder and/or other concurrent medical condition that, in the opinion of the investigator, might compromise safety and/or compliance with study requirements.
• History of alcohol or other substance abuse or dependence within the past two years
• Any significant systemic illness or unstable medical condition that could affect study compliance, including a history of prolonged QTc
• Laboratory abnormalities in B12, TSH, or other common laboratory parameters that might contribute to cognitive dysfunction
• Current use of medications with psychoactive properties that may deleteriously affect cognition (e.g., anticholinergics, antihistamines, antipsychotics, sedative hypnotics, anxiolytics) that, in the opinion of the investigator, may deleteriously affect cognition. Use of other investigational agents one month prior to entry and for the duration of the study
• Treatment with any of the following agents/classes within the past 3 months: simvastatin, antiepileptic agents, clopidogrel, voriconazole, systemic ketoconazole, cyclosporine, St. John's Wort.

Sponsors & Collaborators

• Case Western Reserve University: lead
• University Hospitals Cleveland Medical Center: collaborator
• Massachusetts General Hospital: collaborator

Study Sites (1)

University Hospitals Brain Health and Memory Center

Beachwood, Ohio, 44122, United States

Location

Related Publications (40)

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MeSH Terms

Conditions

Alzheimer Disease

Interventions

efavirenz

Condition Hierarchy (Ancestors)

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

Study Officials

• Irina A Pikuleva, PhD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only the Statistician and Pharmacists are unmasked
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 15, 2018
• First Posted: October 16, 2018
• Study Start: May 5, 2018
• Primary Completion: January 28, 2022
• Study Completion: January 28, 2022
• Last Updated: February 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)