Efficacy and Safety of Tamibarotene (OAM80) for 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: NCT01120002
Recruitment Status : Unknown
Verified July 2011 by Osaka City University.
Recruitment status was:  Recruiting
First Posted : May 10, 2010
Last Update Posted : July 22, 2011
Information provided by:
Osaka City University

Brief Summary:
A double blind, placebo-controlled randomized study to evaluate the efficacy and safety of orally administered Tamibarotene to patients of Alzheimer's Disease

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Tamibarotene Drug: Placebo Phase 2

Detailed Description:

Tamibarotene is a synthetic retinoid presently approved in Japan for the treatment of APL, which has a higher receptor selectivity and activity for the Retinoic Acid Receptor subtypes compared to the natural retinoid.

Tamibarotene decreased insoluble amyloid-beta (Ab) 42 deposition in APP mice, and also increased TTR, VAChT and ACh in the brain of SAMP8 mice, which suggest the enhancement of neurotransmission. In the behavioral model such as reduced anxiety of SAMP8 mice and rat passive avoidance test, tamibarotene showed improvement.

Tamibarotene as in other retinoids are known to moderate the immune system and reduce inflammatory cytokines and chemokines, which may control the excessive stimulation of astrocyte and microglia around the Ab plaque. Tamibarotene reduced cytokines and showed clinical efficacy in the rat experimental autoimmune encephalitis model.

Furthermore, retinoids are known to have critical roles during the regeneration stage in the differentiation from neural stem cells (NSC).

In spinal cord injured rats treated with tamibarotene showed better recovery compared to the control.

By these preclinical results, we plan by this study to evaluate the efficacy together with the safety of tamibarotene to the patients of Alzheimer's Disease.

Tamibarotene is used clinically in Japan since 2005. It's side effects are known to be similar to that of other clinically used retinoids.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Study Start Date : May 2010
Estimated Primary Completion Date : December 2012
Estimated Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo pill Drug: Placebo
Two Tamibarotene 2 mg or placebo tablet per day, once daily.

Active Comparator: Tamibarotene Drug: Tamibarotene
Two Tamibarotene 2 mg or placebo tablet per day, once daily.

Primary Outcome Measures :
  1. Changes in Alzheimer's Disease Assessment Scale (ADAS-JCog) [ Time Frame: baseline, 12 weeks, 24 weeks ]

Secondary Outcome Measures :
  1. Changes in Mini-Mental State Examination (MMSE) [ Time Frame: baseline, 12 weeks, 24 weeks ]
  2. Changes in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) [ Time Frame: baseline, 12 weeks, 24 weeks ]
  3. Changes in Clinician Interview-Based Assessment of Change Plus Caregiver Information (CIBIC-Plus) [ Time Frame: baseline, 12 weeks, 24 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Japanese patients who are diagnosed as probable Alzheimer' Disease according to NINCDS-ADRDA criteria
  • Diagnosed by brain diagnostic imaging (CT, MRI) within six months before the consent and no occurrence of the event after that to suggest cerebral vascular disease
  • Mild to Moderate Alzheimer's Disease of MMSE from 10 to 26
  • Age from 55 to 80
  • Treated for a minimum of 12 weeks with a stable dose of donepezil and willing to continue the same during the trial period
  • For women Menopause ≥ 2 years
  • For men contraceptive measures are required during the study and after 6 months
  • In principle patients should be living at their home in the presence of a caregiver who is defined as a healthy person in contact with the patient for more than 10 hours a week, could provide required information of the behavior and activities of daily living, accompany all the clinical examination, and supervise the handling and administration of the drug throughout the study period.
  • Patients who could take pills as a whole
  • Patient, caregiver and patient surrogate are able and willing to comply with study visits and procedures per protocol, understand, sign, and date the written voluntary informed consent form

Exclusion Criteria:

  • Any cause of dementia not due to Alzheimer's disease
  • Past history of other central nervous condition or psychiatric disease
  • Symptom of depression and drug addiction
  • Impairment in the physical function by other factor than the Alzheimer's Disease
  • Patients who are expected to move in to care facilities during the study period
  • triglyceride > 400 mg/dL

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): NCT01120002

Contact: Takami Miki, MD +81-6-6645-212 ""miki.""

Osaka City University Hospital Recruiting
Osaka, Japan, 545-8586
Contact: Center for Drug&Food Clinical Evaluation    +81-6-6645-344   
Sponsors and Collaborators
Osaka City University
Principal Investigator: Takami Miki, M.D. Department of Geriatrics and Neurology, Osaka City University Graduate School of Medicine

Responsible Party: Takami Miki, MD, Professor, Department of Geriatrics and Neurology, Osaka City University Graduate School of Medicine Identifier: NCT01120002     History of Changes
Other Study ID Numbers: OAM80-01
First Posted: May 10, 2010    Key Record Dates
Last Update Posted: July 22, 2011
Last Verified: July 2011

Keywords provided by Osaka City University:
mild to moderate Alzheimer's Disease

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders