UMIN-CTR Clinical Trial

Public title

Effectiveness of aripiprazole augmentation therapy in patients with bipolar depression who do not respond to mood stabilizers: A randomized, double-blind, placebo-controlled study

Acronym

Effectiveness of AripipRazole THerapy in Bipolar Depression (EARTH BD)

Scientific Title

Effectiveness of aripiprazole augmentation therapy in patients with bipolar depression who do not respond to mood stabilizers: A randomized, double-blind, placebo-controlled study

Scientific Title:Acronym

Effectiveness of AripipRazole THerapy in Bipolar Depression (EARTH BD)

Region

Japan

Condition

Treatment resistant bipolar depression

Classification by specialty

Psychiatry

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

We examine the efficacy of aripiprazole augmentation in patients with bipolar depression who had inadequate response to mood stabilizers using a randomized, double-blind, placebo-controlled study.
We also evaluate the safety of aripiprazole and the effects of plasma catecholamine metabolites, plasma brain- derived neurotrophic factor, plasma cytokines (IL-6, IL-2, IL-1beta, TNF-alpha) and gene polymorphisms on aripiprazole to predict response to the treatment in this study.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Mean change of Montgomery-Asberg Depression Rating Scale (MADRS) for 8 weeks in double-blind phase (from Week 2 to Week 10) in aripiprazole group and placebo group (LOCF).

Key secondary outcomes

Mean change of The Japanese version of Young Mania rating scale (YMRS-J), Clinical global impression;Severity (CGI-S) and Quick Inventory of Depressive Symptomatology (QIDS-J)
(at Week 2, 6, 10)
Mean change of Body mass index (BMI), body weight, and laboratory values (at Week 2, 10)

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is considered as a block.

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

The patients receive single-blind, adjunctive placebo for 2 weeks after patients achieve adequate dose or target blood levels. When it is not fully responded with mood stabilizers (lithium valproate, lamotorigine), aripiprazole is added for 8 weeks in patients with bipolar depression.

Interventions/Control_2

The patients receive single-blind, adjunctive placebo for 2 weeks after patients achieve adequate dose or target blood levels. When it is not fully responded with mood stabilizers (lithium, valproate, lamotorigine), placebo is added for 8 weeks in patients with bipolar depression.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

18

years-old

<=

Age-upper limit

65

years-old

>

Gender

Male and Female

Key inclusion criteria

1) Screening phase
Patients who meet DMS-IV-TR criteria for bipolar disorder
Both male and female outpatients/inpatients aged at 18-65 years.
Patients who have a MADRS total score of 20 or greater and a YMRS total score of 12 or less at baseline.
Patients who have received mood stabilizers (Li, VPA, or LTG) for 4 weeks prior to this study.
Patients who have achieved serum Li levels of 0.7 mEq/L or blood VPA levels of 50 ug/mL..
Patients who have received LTG at 200 mg/day or greater for 2 weeks.
Patients providing written informed consent.

2) Double-blind phase (adjunctive phase)
Patients who meet the above inclusion criteria.
Patients who have a MADRS total score of 20 or greater and a YMRS total score of 12 or less at baseline.
Patients who have less than 20% improvement in MADRS for the screening phase.

Key exclusion criteria

Patients who meet DSM-IV-TR for significant Axis I and II disorders except bipolar disorder.
Patients who received antipsychotics or antidepressants within 4 weeks prior to screening phase.
Patients who have a ECT therapy within 3 months prior to screening phase.
Patients who are comatose and strongly affected by central nervous system depressants such as barbiturates or anesthetics.
Patients who have received adrenaline.
Patients known to have a history or complication of allergy to aripiprazole.
Patients with a history or a complication of diabetes.
Women who are pregnant, possibly pregnant, or breast-feeding.
Patients who have been judged by the investigator to be inappropriate for inclusion in the trial for any other reasons
Patients who have a complication of serious physical disorder.
Patients who have been judged by the investigators to have a high risk of suicide.

Target sample size

93

Name of lead principal investigator

1st name
Middle name
Last name	MASAKI KATO

Organization

Kansai Medical University

Division name

Department of Neuropsychiatry

Zip code

Address

11-15 Fumizonocho Moriguchi, Osaka

TEL

06-6992-1001

Email

katom@takii.kmu.ac.jp

Name of contact person

1st name
Middle name
Last name	MASAKI KATO

Organization

Kansai Medical University

Division name

Department of Neuropsychiatry

Zip code

Address

10-15, Fumizono-cho, Moriguchi City, Osaka

TEL

06-6992-1001

Homepage URL

Email

katom@takii.kmu.ac.jp

Institute

Kansai Medical University

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Department of Psychiatry, University of Occupational and Environmental Health

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

関西医科大学（大阪府）　　　　　　　　　Kansai Medical University
産業医科大学 (福岡県)　　　　 University of Occupational and Environmental Health

Date of disclosure of the study information

2012

Year

04

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2012

Year

07

Month

01

Day

Date of IRB

Anticipated trial start date

2012

Year

08

Month

01

Day

Last follow-up date

2014

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2012

Year

03

Month

06

Day

Last modified on

2015

Year

03

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000008787