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

NCT01560585 | Terminated Phase 1 Results DMC

• 1 other identifier: ISOTRT-01
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer's Disease

Keywords

Isotretinoin; Alzheimer's disease; Dementia; Retinoid

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Number of Adverse Effects

  28 weeks

Study Arms (1)

Open label

EXPERIMENTAL

All participants will receive Isotretinoin for 24 weeks

Drug: Isotretinoin

Interventions

Isotretinoin DRUG

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

Open label

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead

Study Sites (1)

Parkway Medical Building

Beachwood, Ohio, 44122, United States

Location

Related 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.

  PMID: 19903021 BACKGROUND

Related Links

• University Hospitals Case Medical Center

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

Isotretinoin

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Results Point of Contact

• Title: Alan J Lerner,MD
• Organization: University Hospitals Cleveland Medical Center - Cleveland, OH

alan.lerner@uhhospitals.org

1 216 464 6449

Study Officials

• Alan J Lerner, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: "open label study" before being prematurely terminated
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Brain Health and Memory Center, Neurological Institute

Study Record Dates

• First Submitted: March 15, 2012
• First Posted: March 22, 2012
• Study Start: April 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: June 15, 2022
• Results First Posted: June 15, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)