Open Label Study of Isotretinoin in Mild to Moderate Alzheimer's Disease

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Alan Lerner, MD, University Hospital Case Medical Center
ClinicalTrials.gov Identifier:
NCT01560585
First received: March 15, 2012
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

This is an open label study of isotretinoin, a medication which is FDA approved for treatment of other conditions to determine initial safety in Alzheimer's disease.


Condition Intervention Phase
Alzheimer's Disease
Drug: Isotretinoin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label Study of Isotretinoin in Mild to Moderate Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by University Hospital Case Medical Center:

Primary Outcome Measures:
  • Change from Baseline to Six month timepoint in the score on the Alzheimer's disease Assessment Scale- Cognitive subscale [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number and types of adverse effects [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Any adverse events reported by subject or study partner will be recorded at each visit after screening (Baseline, and visits at week 4, 8, 12, 16, 20, 24, and 28 (four weeks after treatment discontinuation).


Estimated Enrollment: 10
Study Start Date: April 2012
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open label
All participants will receive Isotretinoin for 24 weeks
Drug: Isotretinoin
Isotretinoin 0.5 mg per kilogram body weight (rounded to nearest 10 mg) per day for 24 weeks

  Eligibility

Ages Eligible for Study:   50 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Probable AD by DSM IV and NINCDS-ADRDA criteria
  • Females must be surgically sterile (bilateral tubal ligation, both ovaries removed or hysterectomy) or post-menopausal for at least 2 years.
  • > 50 years of age
  • Residing in the community at baseline (includes assisted living facilities, long-term care nursing facilities)
  • Mini Mental State Examination at screen of 12-26 (inclusive)
  • No medical contraindications to study participation
  • Fluent in English at least 8 years of education.
  • Supervision available for study medication. Caregiver/study partner to accompany participant to all visits. Study partner must have direct contact with the participant > 2 days/week
  • Able to ingest oral medication.
  • Neuroimaging (CT or MRI or PET) consistent with the diagnosis of AD at some time after the onset of the memory decline.
  • Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator
  • Stable use of cholinesterase inhibitors and memantine is permitted if doses are stable for 3 months prior to enrollment. Dose should be stable throughout the study unless it is clinically necessary to adjust the medication.
  • Stable use of anti-depressants is permitted if doses are stable for 3 months prior to enrollment. Dose should be stable throughout the study unless it is clinically necessary to adjust the medication.

Exclusion Criteria:

  • Dementia not due to probable Alzheimer's disease
  • Pregnancy, breastfeeding. The rationale is that retinoids are teratogenic and are excreted in breast milk.
  • History of clinically significant stroke
  • Modified Hachinski Ischemia score ≥ 4
  • Current evidence or history in past two years of epilepsy, seizure, focal brain lesion, head injury with loss of consciousness or DSM IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, severe alcohol or substance abuse.
  • Sensory impairment which would prevent subject from participating in or cooperating with the protocol.
  • Use of another investigational agent within two months.
  • Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational new drug including clinically significant or unstable hematologic, hepatic, cardiovascular (including history of ventricular fibrillation or ventricular tachycardia), pulmonary, gastrointestinal, endocrine, metabolic, renal, or other systemic disease or laboratory abnormality. Abnormal liver function test, including AST, ALT, total bilirubin, or prothrombin time. The rationale is that retinoids can be hepatotoxic.
  • Participants receiving behavioral medications (including antidepressants, antipsychotics and anxiolytics) must be on stable doses for at least 4 weeks prior to randomization.
  • Active neoplastic disease and any medical conditions requiring concurrent immunosuppression.
  • Hypertriglyceridemia greater than 500 mg/dL despite statin/fibrate therapy. The rationale is that retinoids can increase lipids, particularly triglyceride and this can lead to pancreatitis.
  • Any medical conditions requiring concurrent use of tetracycline, minocycline, or doxycycline. The rationale is due to enhanced risk of increased intracranial pressure.
  • Hypersensitivity to retinoids.
  • Presence of psychosis or hallucinations at baseline as determined by Neuropsychiatric inventory or Geriatric Depression Scale-short form greater than or equal to five
  • Presence of any unstable cardiovascular disease, uncontrolled diabetes, chronic inflammatory or infectious conditions. Retinoids have been associated with chest pain of unclear etiology, increased serum glucose, myelosuppression and increased risk of infection.
  • Use of Drugs and supplements such as: Vitamin A supplements beyond 100% RDA, other immunosuppressants (corticosteroids, chemotherapeutic agents, etc.), Warfarin , Fish Oil (DHA)
  • Any other disease or medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this clinical trial.
  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: NCT01560585

Locations
United States, Ohio
Parkway Medical Building
Beachwood, Ohio, United States, 44122
Sponsors and Collaborators
University Hospital Case Medical Center
Investigators
Principal Investigator: Alan J Lerner, MD University Hospital Case Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Alan Lerner, MD, Director, Brain Health and Memory Center, Neurological Institute, University Hospital Case Medical Center
ClinicalTrials.gov Identifier: NCT01560585     History of Changes
Other Study ID Numbers: ISOTRT-01
Study First Received: March 15, 2012
Last Updated: August 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University Hospital Case Medical Center:
Isotretinoin
Alzheimer's disease
Dementia
Retinoid

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Isotretinoin
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014