Clinical trial NCT02061878: A Study to Evaluate the Effect of Bexarotene on Beta-Amyloid and Apolipoprotein E Metabolism in Healthy Subjects
Official title: A Randomized Controlled Study to Evaluate the Effect of Bexarotene - an RXR Agonist - on Beta-Amyloid and Apolipoprotein E Metabolism in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Keywords: ApoE
beta-amyloid
Lead sponsor: ReXceptor, Inc.
Sponsor class: INDUSTRY
First posted: 2014-02-13
Enrollment: 12
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The primary objective of this proof of mechanism pilot clinical trial is to determine if the RXR agonist bexarotene acts in humans to alter the CSF levels of apoE and alter the clearance of Amyloid-Beta

Detailed description: This is a double blinded, investigational drug study designed to measure the effect of bexarotene on the clearance of Aβ total and production of apoE in the human brain of young, healthy individuals with the APOE3/3 genotype. From the date of initial subject recruitment to the issuance of a final study report and closeout activities, the expected total study duration is 6 to 10 months.

Each participant will be screened for eligibility and randomized to receive either oral bexarotene or placebo control ("Test Article").The study has the potential to demonstrate the pharmacodynamic properties of a novel treatment approach to Alzheimer's disease. The primary biomarker measurements obtained from this study are believed to be highly dynamic and able to provide a rapid read-out of the biologic activity of the candidate therapeutic under study. In addition, exploratory analysis will involve a proteomics-based screen to identify proteins within both blood and CSF that are induced by the Test Article, thereby potentially identifying new biomarkers that can be used in future clinical trials to demonstrate bexarotene action and target engagement.

Eligibility criteria: Inclusion Criteria:

* Young healthy adults (age 21-50)
* APOE3/3 genotype

Exclusion Criteria:

* Contraindications for blood or CSF sampling
* Bleeding disorder or taking anticoagulants/antiplatelets
* Chronic active infection
* Blood donation within the past month
* Active drug/alcohol dependence or abuse history with in the last 12 months
* Thyroid dysfunction
* High triglycerides (\>3.5 mmol/L)
* High cholesterol (\>4.0 mmoL/L)
* Leukopenia, including low neutrophil count (\<3 x 10\^9/L)
* Neurological or psychiatric disorders
* Homeless or prisoner
* Pregnancy
* Incapable of self-informed consent
* Blood borne disease (HIV, Hepatitis)
* Actively smoking and incapable of using nicotine patches
* Known drug allergy to pain medication or local anesthetic
* Subjects that have participated in another study in the last 30 days
* Abnormalities in lumbar spine previously known within 12 months
* APOE2 or APOE4 allele
* Abnormal EKG

Primary outcomes:
measure: Area under the effect curve for newly generated beta-Amyloid (clearance phase),
timeFrame: 21 - 48 hr
Secondary outcomes:
measure: Fractional clearance rate of beta-Amyloid peptide in CNS
timeFrame: 21 - 36 hrs
Other outcomes:
measure: Exploratory Endpoint
timeFrame: 5 days
Locations:
city: Orlando
country: United States
facility: Compass Research
state: Florida
Study officials:
affiliation: Compass Research
name: Craig T Curtis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ghosal K, Haag M, Verghese PB, West T, Veenstra T, Braunstein JB, Bateman RJ, Holtzman DM, Landreth GE. A randomized controlled study to evaluate the effect of bexarotene on amyloid-beta and apolipoprotein E metabolism in healthy subjects. Alzheimers Dement (N Y). 2016 Jun 17;2(2):110-120. doi: 10.1016/j.trci.2016.06.001. eCollection 2016 Jun.