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

• Sponsor: University Hospitals Cleveland Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01560585
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arm: 1
• Actual Duration (Months): 28
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Detailed 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

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: "open label study" before being prematurely terminated
• Primary Purpose: Treatment
• Official Title: Open Label Study of Isotretinoin in Mild to Moderate Alzheimer's Disease
• Actual Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Six Month Timepoint in the Score on the Alzheimer's Disease Assessment Scale- Cognitive Subscale [6 months from baseline]

   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

Secondary Outcome Measures

1. Number of Adverse Effects [28 weeks]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 90 Years
• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parkway Medical Building	Beachwood	Ohio	United States	44122

Sponsors and Collaborators

• University Hospitals Cleveland Medical Center

Investigators

• Principal Investigator: Alan J Lerner, MD, University Hospitals Cleveland Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University Hospitals Case Medical Center

Publications

• 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.

• Responsible Party: Alan Lerner, MD, Director, Brain Health and Memory Center, Neurological Institute, University Hospitals Cleveland Medical Center
• ClinicalTrials.gov Identifier: NCT01560585
• Other Study ID Numbers: ISOTRT-01
• First Posted: Mar 22, 2012
• Last Update Posted: Jun 15, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Alan Lerner, MD, Director, Brain Health and Memory Center, Neurological Institute, University Hospitals Cleveland Medical Center: Isotretinoin; Alzheimer's disease; Dementia; Retinoid
• Additional relevant MeSH terms: Alzheimer Disease; Isotretinoin

Study Results

Participant Flow

Recruitment Details	Recruited from clinical population of PI

Arm/Group Title	Open Label
Arm/Group Description	All participants will receive Isotretinoin for 24 weeks Isotretinoin: Isotretinoin 0.5 mg per kilogram body weight (rounded to nearest 10 mg) per day for 24 weeks
Period Title: Overall Study
STARTED	3
Screened	3
COMPLETED	0
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Open Label
Arm/Group Description	All participants will receive Isotretinoin for 24 weeks Isotretinoin: Isotretinoin 0.5 mg per kilogram body weight (rounded to nearest 10 mg) per day for 24 weeks
Overall Participants	3
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	3 100%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	3 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	3 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	3 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%
impaired cognition due to alzheimer's disease diagnosis (Count of Participants)
Count of Participants [Participants]	3 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Six Month Timepoint in the Score on the Alzheimer's Disease Assessment Scale- Cognitive Subscale
Description	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
Time Frame	6 months from baseline

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	Open Label Treatment
Arm/Group Description	All participants will receive Isotretinoin for 24 weeks
Measure Participants	0

2. Secondary Outcome

Title	Number of Adverse Effects
Description	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).
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label
Arm/Group Description	All participants will receive Isotretinoin for 24 weeks Isotretinoin: Isotretinoin 0.5 mg per kilogram body weight (rounded to nearest 10 mg) per day for 24 weeks
Measure Participants	3
Number [Number of events]	2

Adverse Events

Arm/Group Title	Open Label Treatment
Arm/Group Description	Study terminated due to adverse events leading to PI decision to terminate study
All Cause Mortality
	Open Label Treatment
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Serious Adverse Events
	Open Label Treatment
	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
neoplasm	1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	Open Label Treatment
	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)
Nervous system disorders
loss of consciousness	1/3 (33.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.