A Study to Evaluate the Effect of Bexarotene on Beta-Amyloid and Apolipoprotein E Metabolism in Healthy Subjects

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02061878
• Other study ID #: REXCEPTOR-101
• Status: Completed
• Phase: Phase 1
• First received: February 5, 2014
• Last updated: August 11, 2015
• Start date: August 2014
• Est. completion date: November 2014

Study information

• Verified date: August 2015
• Source: ReXceptor, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Bexarotene
Marketed product Targretin® soft gelatin capsule (75mg/capsule) is over-encapsulated in a size AA-el Swedish orange capsule. The subjects will be administered three (3) capsules of Targretin™ (75 mg/capsule) on a twice daily basis (450 mg/day) for five days.
• Placebo
The subjects will be administered three (3) capsules of Avicel PH on a twice daily basis (450 mg/day) for five days.

Locations

Country	Name	City	State
United States	Compass Research	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
ReXceptor, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory Endpoint	AUEC0-18 for newly generated beta-Amyloid (production phase)	5 days	No
Primary	Area under the effect curve for newly generated beta-Amyloid (clearance phase),	Area under the effect curve from 21-48h for newly generated beta-Amyloid (clearance phase), which is computed for each individual as the area under the curve of the clearance portion of the labeled beta-Amyloid curve between 21 hour and 48 hours, normalized by plasma free leucine levels.	21 - 48 hr	No
Secondary	Fractional clearance rate of beta-Amyloid peptide in CNS	Fractional clearance rate (FCR) of beta-Amyloid peptide in CNS, computed for each individual as the slope of the natural logarithm of the clearance portion of the labeled beta-Amyloid curve between 21 hours and 36 hours 2) AUEC0-24 of apoE: Area under the effect curve from 0-24h for newly generated apoE (production phase) 3) Fractional synthesis rate (FSR) of apoE protein in CNS 4) Aß and apoE concentrations: CSF beta-Amyloid and apoE concentrations for each time point 5)Size of apoE-containing high density lipoprotein particles in CSF as assessed by native PAGE 6) Labeled/Unlabeled Leu ratio (% of 13C6 Leu) in plasma and CSF for 48 hours following start of 13C6 Leu administration 7) Bexarotene concentrations in blood and CSF 8) Plasma beta-Amyloid total and apoE concentrations at baseline compared to final plasma beta-Amyloid total and apoE concentrations	21 - 36 hrs	No