Efficacy and Safety of Tamibarotene (OAM80) for Alzheimer's Disease

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by Osaka City University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Osaka City University
ClinicalTrials.gov Identifier:
NCT01120002
First received: April 30, 2010
Last updated: July 21, 2011
Last verified: July 2011
  Purpose

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


Condition Intervention Phase
Alzheimer's Disease
Drug: Tamibarotene
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Osaka City University:

Primary Outcome Measures:
  • Changes in Alzheimer's Disease Assessment Scale (ADAS-JCog) [ Time Frame: baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in Mini-Mental State Examination (MMSE) [ Time Frame: baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Changes in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) [ Time Frame: baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Changes in Clinician Interview-Based Assessment of Change Plus Caregiver Information (CIBIC-Plus) [ Time Frame: baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: May 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   55 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01120002

Contacts
Contact: Takami Miki, MD +81-6-6645-212 ""miki."@med.osaka-cu.ac.jp"

Locations
Japan
Osaka City University Hospital Recruiting
Osaka, Japan, 545-8586
Contact: Center for Drug&Food Clinical Evaluation    +81-6-6645-344    morikka@med.osaka-cu.ac.jp   
Sponsors and Collaborators
Osaka City University
Investigators
Principal Investigator: Takami Miki, M.D. Department of Geriatrics and Neurology, Osaka City University Graduate School of Medicine
  More Information

Publications:
Responsible Party: Takami Miki, MD, Professor, Department of Geriatrics and Neurology, Osaka City University Graduate School of Medicine
ClinicalTrials.gov Identifier: NCT01120002     History of Changes
Other Study ID Numbers: OAM80-01
Study First Received: April 30, 2010
Last Updated: July 21, 2011
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

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

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies

ClinicalTrials.gov processed this record on October 23, 2014