Bexarotene Amyloid Treatment for Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Bexarotene; Placebo
Intervention description: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
Intervention MeSH terms: Bexarotene
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 20.0
Sex: All
Minimum age: 50 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Mild to Moderate Alzheimer's Disease

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).
    

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.