Bexarotene Amyloid Treatment for Alzheimer's Disease

NCT ID: NCT01782742

Last Updated: 2016-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2014-12-31

Brief Summary

Retinoid X receptors (RXR) are nuclear receptors that have been linked to numerous metabolic pathways relevant to Alzheimer's disease (AD) and Aβ (harmful protein) production and removal. The study drug "bexarotene" is an FDA approved anti-cancer agent but is not approved for use in Alzheimer's disease. Bexarotene acts as an RXR agonist that has reduced Aβ (harmful protein) in the brain in experimental models of Alzheimer's disease.

This study aims to determine the safety and effect on abnormal proteins found in the brain (based on brain scans) of 300 mg of "bexarotene" administered for one month compared to placebo (inactive agent).

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Bexarotene treatment Arm

75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.

Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)

Group Type: ACTIVE_COMPARATOR

Bexarotene

Intervention Type: DRUG

Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo

Placebo

1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.

Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Bexarotene

Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Targretin

Eligibility Criteria

Inclusion Criteria

• Males or females 50 to 90 of age inclusive.
• Diagnosis of probable AD according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
• Willing and able to provide informed consent by either the subject or subject's legal representative.
• Willing and able to comply with study visits, treatment plan, laboratory tests, brain imaging and other procedures.
• Subjects must have a positive 18f-AV-45 PET scan as determined by a qualified rater.
• Mini-Mental State Examinations (MMSE) score between 10-20 inclusive.
• Must have a study partner who is able and willing to comply with all required study procedures.
• Females must be postmenopausal.
• Have at least eight years of education and should have previously (in pre-AD condition) been capable of reading, writing, and communicating effectively with others in English.
• If receiving therapy with a cholinesterase inhibitor and/or memantine, the dose of these agents has been stable for at least 4 weeks prior to randomization
• Normal laboratory findings at baseline including CBC, chemistry panel, serum lipids, liver functions, TSH, and vitamin B12.
• Must consent to ApoE genotyping

Exclusion Criteria

• Any clinically relevant neurological disorder capable of producing a dementia syndrome including Parkinson's disease, stroke, vascular dementia, dementia with Lewy bodies, frontotemporal dementia and others.
• 4 or more micro-hemorrhages (amyloid-related imaging abnormalities - hemorrhage type (ARIA-H) on baseline MRI or any evidence of amyloid-related imaging abnormalities - effusion type (ARIA-E) (Sperling et al, 2011).
• History of malignancy within the past five years with the exception of basal cell or squamous cell cancer, in-situ cervical cancer, or localized prostate cancer.
• History of seizure in the past three years prior to randomization
• Any contraindication of having brain MRI
• Any contraindication of having PET (inability to lie flat and still for the duration of the scan, intolerance to previous PET such as hypersensitivity reaction to PET ligand or imaging agent)
• The subject has any unstable medical illness including hypertension, congestive heart failure, chronic obstructive pulmonary disease, renal failure, liver failure or other organ compromise.
• Other clinically important abnormality on vital signs, physical examination, neurologic examination, laboratory results, or electrocardiogram (ECG) examination (e.g. Atrial fibrillation) that could compromise the study or be detrimental to the subject.
• The subject has received bexarotene previously.
• The subject has an allergy to bexarotene.
• Has had a PET scan in the past 12 months.
• Has had radiotherapy in the past year.
• Have participated in an investigational drug or device study within 30 days prior to Visit 2.
• Have been treated with immunomodulators to treat AD (vaccines, antibodies etc) within 6 months prior to visit 2
• Unable to swallow uncrushed oral medication in capsule form
• Have any condition or reason that, in the opinion of the investigator, which could interfere with the ability of the patients to participate or complete the trials, or places the patient at undue risk or complicates the interpretation of safety or efficacy data.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey L Cummings, MD, ScD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, United States

Countries

United States

References

Cummings JL, Zhong K, Kinney JW, Heaney C, Moll-Tudla J, Joshi A, Pontecorvo M, Devous M, Tang A, Bena J. Double-blind, placebo-controlled, proof-of-concept trial of bexarotene Xin moderate Alzheimer's disease. Alzheimers Res Ther. 2016 Jan 29;8:4. doi: 10.1186/s13195-016-0173-2.

Reference Type: DERIVED

PMID: 26822146 (View on PubMed)

Other Identifiers

CCF-IRB 12-783

Identifier Type: -

Identifier Source: org_study_id