Trial record 12 of 43 for:    bexarotene

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by ReXceptor, Inc.
Sponsor:
Information provided by (Responsible Party):
ReXceptor, Inc.
ClinicalTrials.gov Identifier:
NCT02061878
First received: February 5, 2014
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention Phase
Alzheimer's Disease
Drug: Bexarotene
Drug: Placebo
Phase 1

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

Resource links provided by NLM:


Further study details as provided by ReXceptor, Inc.:

Primary Outcome Measures:
  • Area under the effect curve for newly generated beta-Amyloid (clearance phase), [ Time Frame: 21 - 48 hr ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Fractional clearance rate of beta-Amyloid peptide in CNS [ Time Frame: 21 - 36 hrs ] [ Designated as safety issue: No ]
    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) Aβ 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


Other Outcome Measures:
  • Exploratory Endpoint [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    AUEC0-18 for newly generated beta-Amyloid (production phase)


Estimated Enrollment: 12
Study Start Date: February 2014
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bexarotene
The subjects will be administered three (3) capsules of Targretin™ (75 mg/capsule) on a twice daily basis (450 mg/day) for five days
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.
Other Name: Targretin®
Placebo Comparator: Placebo
The subjects will be administered three (3) capsules of Avicel PH on a twice daily basis (450 mg/day) for five days.
Drug: Placebo
The subjects will be administered three (3) capsules of Avicel PH on a twice daily basis (450 mg/day) for five days.
Other Name: Avicel PH

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

Ages Eligible for Study:   21 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02061878

Contacts
Contact: Gary Landreth 2163686101 gel2@case.edu

Locations
United States, Florida
Compass Research Not yet recruiting
Orlando, Florida, United States, 32806
Sponsors and Collaborators
ReXceptor, Inc.
Investigators
Principal Investigator: Craig T Curtis, MD Compass Research
  More Information

No publications provided

Responsible Party: ReXceptor, Inc.
ClinicalTrials.gov Identifier: NCT02061878     History of Changes
Other Study ID Numbers: REXCEPTOR-101
Study First Received: February 5, 2014
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by ReXceptor, Inc.:
ApoE
beta-amyloid

Additional relevant MeSH terms:
Bexarotene
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Anticarcinogenic Agents
Antineoplastic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2015