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

Sponsor

Osaka City University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01120002

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Anticipated 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 1, 2010

Anticipated Primary Completion Date :

Dec 1, 2012

Anticipated Study Completion Date :

Dec 1, 2012

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Changes in Alzheimer's Disease Assessment Scale (ADAS-JCog) [baseline, 12 weeks, 24 weeks]

Secondary Outcome Measures

Changes in Mini-Mental State Examination (MMSE) [baseline, 12 weeks, 24 weeks]
Changes in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) [baseline, 12 weeks, 24 weeks]
Changes in Clinician Interview-Based Assessment of Change Plus Caregiver Information (CIBIC-Plus) [baseline, 12 weeks, 24 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Osaka City University Hospital	Osaka		Japan	545-8586

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Shudo K, Fukasawa H, Nakagomi M, Yamagata N. Towards retinoid therapy for Alzheimer's disease. Curr Alzheimer Res. 2009 Jun;6(3):302-11. Review.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT01120002

Other Study ID Numbers:

OAM80-01

First Posted:

May 10, 2010

Last Update Posted:

Jul 22, 2011

Last Verified:

Jul 1, 2011

Keywords provided by , ,

mild to moderate Alzheimer's Disease

Additional relevant MeSH terms:

Alzheimer Disease

Study Results

No Results Posted as of Jul 22, 2011