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

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01560585
• Other study ID #: ISOTRT-01
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 2012
• Est. completion date: August 2014

Study information

• Verified date: May 2022
• Source: University Hospitals Cleveland Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Retinoids have some relevant characteristics that could be considered useful in treating AlZheimer's disease. These include anti-inflammatory properties, possible anti-amyloid formation proeprties and inhibition of cell cycle properties

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Isotretinoin
Isotretinoin 0.5 mg per kilogram body weight (rounded to nearest 10 mg) per day for 24 weeks

Locations

Country	Name	City	State
United States	Parkway Medical Building	Beachwood	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
University Hospitals Cleveland Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lee HP, Casadesus G, Zhu X, Lee HG, Perry G, Smith MA, Gustaw-Rothenberg K, Lerner A. All-trans retinoic acid as a novel therapeutic strategy for Alzheimer's disease. Expert Rev Neurother. 2009 Nov;9(11):1615-21. doi: 10.1586/ern.09.86. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Six Month Timepoint in the Score on the Alzheimer's Disease Assessment Scale- Cognitive Subscale	Alzheimer's disease Assessment Scale- Cognitive subscale is a scale to measure cognitive function used in dementia clinical trials. No primary outcome data since study was terminated before any participaant completed	6 months from baseline
Secondary	Number of Adverse Effects	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).	28 weeks

External Links

•   University Hospitals Case Medical Center