AGTs-BD: Algorithm Guided Treatment Strategies for Bipolar Depression

Sponsor

Shanghai Mental Health Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT01938859

Collaborator

(none)

360

Enrollment

Location

Arms

Anticipated Duration (Months)

4.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the AGTs-BD study is to compare the treatment outcome and safety profiles between different mood stabilizers combination treatments in the patients with bipolar disorders, currently suffered from depression episode.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Lithium Drug: Quetiapine Drug: Shuganjieyu capsule	Phase 4

Detailed Description

The AGTs-BD study is a randomized, open-label, rater-blind, multicenter study, which including an 8-week acute treatment (Phase I), followed by a 24-week recurrence prevention treatment (Phase II), and a 24-week relapse prevention treatment (Phase III). Patients initially enter an up to 4 weeks screening phase to confirm the randomization to whom met DSM-IV criteria of bipolar I or II disorder, currently depressed with Hamilton Depression Rating Scale-17 items (HAM-D) total score ≥17. The protocol was approved by the each sites' appropriate institutional review boards and ethics committees. After screening, patients were randomly allocated to one of three groups: (1) lithium monotherapy; (2) lithium plus quetiapine; (3) lithium plus a Traditional Chinese Medicine (TCM) named as Shuganjieyu capsule (SGJY, St. John's wort and acanthopanax senticosus combination). After phase I, patients who met stable remission, defined as HAM-D total score ≤7 and Young Mania Rating Scale (YMRS) total score ≤10 in two consecutive visit at least 4 weeks, were qualified into phase II and III. Patients remained on the allocated treatment for up to 48 weeks or until treatment failure. The difference between phase II and phase III was that treatment dose could be decreased (within the study ranges) if side-effects became troublesome in phase III, but not for phase II. All patients will be provided with free care (3 visits) by the investigators, for a period of up to 3 months after the end of the study, in order to help them make the transition into routine clinical care.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

360 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Algorithm Guided Treatment Strategies for Bipolar Depression

Actual Study Start Date :

Jun 1, 2012

Anticipated Primary Completion Date :

Dec 1, 2017

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lithium combined with SGAs SGAs (Second Generation Antipsychotics), quetiapine adjunctive to lithium therapy	Drug: Lithium Lithium plasma concentration was between 0.6-1.2 mmol/L, dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability. Drug: Quetiapine Quetiapine adjunctively to lithium therapy, target 400 mg/d with a minimum dose of 200 mg/d. Dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability.
Experimental: lithium combined with TCM TCM (Traditional Chinese Medicine), Shuganjieyu capsule adjunctive to lithium therapy.	Drug: Lithium Lithium plasma concentration was between 0.6-1.2 mmol/L, dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability. Drug: Shuganjieyu capsule Shuganjieyu capsule adjunctively to lithium therapy, target dose 1440 mg/d. Other Names: SGJY, St.John's wort and acanthopanax senticosus combination
Active Comparator: Lithium monotherpy Lithium monotherapy	Drug: Lithium Lithium plasma concentration was between 0.6-1.2 mmol/L, dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability.

Arm

Intervention/Treatment

Experimental: Lithium combined with SGAs

SGAs (Second Generation Antipsychotics), quetiapine adjunctive to lithium therapy

Drug: Lithium

Lithium plasma concentration was between 0.6-1.2 mmol/L, dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability.

Drug: Quetiapine

Quetiapine adjunctively to lithium therapy, target 400 mg/d with a minimum dose of 200 mg/d. Dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability.

Experimental: lithium combined with TCM

TCM (Traditional Chinese Medicine), Shuganjieyu capsule adjunctive to lithium therapy.

Drug: Lithium

Lithium plasma concentration was between 0.6-1.2 mmol/L, dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability.

Drug: Shuganjieyu capsule

Shuganjieyu capsule adjunctively to lithium therapy, target dose 1440 mg/d.

Other Names:

SGJY, St.John's wort and acanthopanax senticosus combination

Active Comparator: Lithium monotherpy

Lithium monotherapy

Drug: Lithium

Lithium plasma concentration was between 0.6-1.2 mmol/L, dose should be fixed at the end of week 4, and the maximum dosage was judged by the investigator based on the patients' tolerability.

Outcome Measures

Primary Outcome Measures

The change of HAM-D total score only for the phase I [baseline and 8 weeks]
Time to new intervention for an emerging mood episode [up to 48 weeks]
Time to new intervention for an emerging mood episode is only for Phase II and Phase III, including drug treatment (commencement of a new drug, increase in dose of concurrent drug, restarting of a discontinued drug, or increasing the investigational drug dose in response to an emergent mood episode) or admission to hospital.

Secondary Outcome Measures

HAM-D total score ≤7 [8 weeks for phase I, up to 48 weeks for phase II and III]
Remission rate
Mean changes from baseline to EOS in HAM-D total score ≥50% [8 weeks for phase I, up to 48 weeks for phase II and III]
Response rate
Mean changes from baseline to EOS in 16-item Quick Inventory of Depressive Symptomatology-Patient Self-Report (QIDS16-SR) [8 weeks for phase I, up to 48 weeks for phase II and III]
Mean changes from baseline to EOS in Clinical Global Impression scale of Bipolar Disorder-Severity (CGI-BP-S) [8 weeks for phase I, up to 48 weeks for phase II and III]
Mean changes from baseline to EOS in Sheehan Disability Scale (SDS) [8 weeks for phase I, up to 48 weeks for phase II and III]
Social function
Mean changes from baseline to EOS in 6-item Quality of Life scale (QOL-6) [8 weeks for phase I, up to 48 weeks for phase II and III]
Social function
Young Mania Rating Scale (YMRS) total score ≤10 [8 weeks for phase I, up to 48 weeks for phase II and III]
Using YMRS total score to monitor the switching from depression to hypomania and mania

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age from 18 to 65 years old;
Han Chinese;
Outpatient and inpatient patients;
Patients met DSM-IV criteria of bipolar I or II disorder, currently depressed, ascertained with the Mini International Neuropsychiatric Interview (MINI)
HAM-D total score≥17, HAM-D item 1 (depressed mood) score≥2, and YMRS total score≤10 at baseline;
Written informed consent was given;
Junior high school education and above, with enough audio-visual ability to accomplish the visits;
Normally resident in one country and had a residential address, able to follow-up.

Exclusion Criteria:

Bipolar disorder rapid cycling or mixed episode;
Experienced DSM-IV-TR axis I disorders in the 6 months prior to randomization;
Severe personality disorder, metal retardation, anorexia/bulimia nervosa;
Actively suicide ascertained by research psychiatrist or HAM-D item 3 score≥3(suicidality);
Known history of intolerance or hypersensitivity to any of the medications involved in the study, including lithium, quetiapine and SGJY capsule;
Female patients who were pregnant, planning to be pregnant or breast feeding;
Severe medical or neurological problems.