Series Studies of Bipolar Disorder-Valproate add-on Memantine (MM)

Series Studies of Bipolar Disorder-Valproate add-on Memantine Treatment

All participants should fulfill the following criteria: aged between 18 and 65 years old, and of domestic Han descendants. Participants will be randomly assigned to either the (1) pharmacotherapy (valproate add-on memantine) group; (2) pharmacotherapy (valproate add-on memantine) plus Cognitive Behavior Group Therapy (CBGT) group; (3) valproate add-on placebo plus CBGT group, or (4) valproate add-on placebo only group. A total of 240-320 individuals (60-80 participants per group) will be recruited for this study. For each CBGT group, 12-weekly sessions are scheduled according to patients' preference. The investigators will attempt to understand the effects of pharmaceutical drugs for mood stabilizers add-on neuro-protective drugs, pharmacotherapy with CBGT, mood stabilizer with CBGT, and the use of only traditional mood stabilizers in the treatment of BP II. Comparisons will be made for each type of treatment and possible mechanisms will be examined regarding the pharmacotherapy and CBGT for bipolar disorder patients.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorders
• Intervention / Treatment: Drug: Placebo; Drug: Memantine

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • Ru-Band Lu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patient aged >=18 and <= 65 years.
2. A diagnosis of bipolar II disorder according to DSM-IV-TR criteria made by a specialist in psychiatry.
3. A total of HDRS score at least 18 or YMRS score at least 14 at screen.
4. Signed informed consent by patient or legal representative.

Exclusion Criteria:

1. Women of childbearing potential not using adequate contraception as per investigator judgment or not willing to comply with contraception for duration of study.
2. Females who are pregnant or nursing.
3. Patient has received memantine or other selective cyclo-oxygenase 2 (Cox-2) inhibitors within 1 week prior to first dose of double-blind medication.
4. Axis-I DSM-IV-TR diagnosis other than bipolar II disorder.
5. Current evidence of an uncontrolled and/or clinically significant medical condition (e.g., cardiac, hepatic and renal failure), which in the judgments of the investigator, would compromise patient safety or preclude study participation.
6. History of intolerance to valproate or memantine or other Cox-2 inhibitors.
7. History of sensitivity reaction (e.g., urticaria, angioedema, bronchospasm, severe rhinitis, anaphylactic shock) precipitated by memantine
8. Patient has received electroconvulsive therapy (ECT) within 4 weeks prior to first dose of doubleblind medication.
9. Inclusion in another bipolar disorder study or study for another indication with psychotropic's within the last 30 days prior to start of study.
10. Increase in total SGOT, SGPT, BUN and creatinine by more than 3X ULN (upper limit of normal).
11. Substance-related disorders within 6 months prior to study start, borderline personality disorder, schizophrenia, or other major psychiatric disorders as defined by DSM-IV criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: VPA & Placebo	Drug: Placebo
Experimental: VPA & memantine	Drug: Memantine; 5 mg per day of memantine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Young's Mania Rating Scale (YMRS)	Normally, YMRS is used to evaluate the Bipolar Disorder Patient's mood change.	baseline, 1, 2, 4, 8 and 12 weeks
Hamilton Depression Rating Scale (HDRS)	Normally, YMRS is used to evaluate the Bipolar Disorder Patient's mood change of depression.	baseline, 1, 2, 4, 8 and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cytokines		baseline, 1, 2, 4, 8 and 12 weeks
Clinical Global Impression (CGI)	CGI will be used to evaluate how the patient's adverse effect go on during the trial.	baseline, 1, 2, 4, 8 and the week 12
lipid profiles	HDL, LDL, cholesterol and etc.	baseline, 1, 2, 4, 8 and 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
genetics	ALDH2, ADH1B, COMT, DRD2, DRD3, BDNFVal66Met	baseline

Collaborators and Investigators

• Sponsor: National Cheng-Kung University Hospital
• Collaborators: National Science Council, Taiwan

Publications and helpful links

General Publications

• Lee SY, Chen SL, Chang YH, Chen SH, Chu CH, Huang SY, Tzeng NS, Wang CL, Wang LJ, Lee IH, Yeh TL, Yang YK, Hong JS, Lu RB. Genotype variant associated with add-on memantine in bipolar II disorder. Int J Neuropsychopharmacol. 2014 Feb;17(2):189-97. doi: 10.1017/S1461145713000825. Epub 2013 Oct 9. Erratum In: Int J Neuropsychopharmacol. 2014 Jun;17(6):979. Lu, Ru-Band [removed]; Hong, Jau-Shyong [added].
• Lee SY, Chen SL, Chang YH, Chen PS, Huang SY, Tzeng NS, Wang YS, Wang LJ, Lee IH, Yeh TL, Yang YK, Lu RB, Hong JS. Add-on memantine to valproate treatment increased HDL-C in bipolar II disorder. J Psychiatr Res. 2013 Oct;47(10):1343-8. doi: 10.1016/j.jpsychires.2013.06.017. Epub 2013 Jul 18.
• Lee SY, Chen SL, Chang YH, Chen PS, Huang SY, Tzeng NS, Wang YS, Wang LJ, Lee IH, Wang TY, Yeh TL, Yang YK, Hong JS, Lu RB. Inflammation's Association with Metabolic Profiles before and after a Twelve-Week Clinical Trial in Drug-Naive Patients with Bipolar II Disorder. PLoS One. 2013 Jun 27;8(6):e66847. doi: 10.1371/journal.pone.0066847. Print 2013.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: August 23, 2010
• First Submitted That Met QC Criteria: August 23, 2010
• First Posted (Estimate): August 25, 2010

Study Record Updates

• Last Update Posted (Estimate): September 17, 2013
• Last Update Submitted That Met QC Criteria: September 16, 2013
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: BPMM HR-98-025