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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01560585
Recruitment Status : Terminated
First Posted : March 22, 2012
Last Update Posted : August 28, 2014
Information provided by (Responsible Party):
Alan Lerner, MD, University Hospitals Cleveland Medical Center

Brief Summary:
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 or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Isotretinoin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label Study of Isotretinoin in Mild to Moderate Alzheimer's Disease
Study Start Date : April 2012
Actual Primary Completion Date : August 2014
Actual Study Completion Date : August 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Change from Baseline to Six month timepoint in the score on the Alzheimer's disease Assessment Scale- Cognitive subscale [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Number and types of adverse effects [ Time Frame: 6 months ]
    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).

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   50 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01560585

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United States, Ohio
Parkway Medical Building
Beachwood, Ohio, United States, 44122
Sponsors and Collaborators
University Hospitals Cleveland Medical Center
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Principal Investigator: Alan J Lerner, MD University Hospitals Cleveland Medical Center

Additional Information:
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Responsible Party: Alan Lerner, MD, Director, Brain Health and Memory Center, Neurological Institute, University Hospitals Cleveland Medical Center Identifier: NCT01560585    
Other Study ID Numbers: ISOTRT-01
First Posted: March 22, 2012    Key Record Dates
Last Update Posted: August 28, 2014
Last Verified: August 2014
Keywords provided by Alan Lerner, MD, University Hospitals Cleveland Medical Center:
Alzheimer's disease
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Dermatologic Agents