Clinical trial NCT01188148: Series Studies of Bipolar Disorder-Valproate add-on Memantine
Official title: Series Studies of Bipolar Disorder-Valproate add-on Memantine Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Bipolar Disorders
Lead sponsor: National Cheng-Kung University Hospital
Sponsor class: OTHER
Collaborators: name: National Science and Technology Council, Taiwan
First posted: 2010-08-25
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Young's Mania Rating Scale (YMRS)
timeFrame: baseline, 1, 2, 4, 8 and 12 weeks
measure: Hamilton Depression Rating Scale (HDRS)
timeFrame: baseline, 1, 2, 4, 8 and 12 weeks
Secondary outcomes:
measure: cytokines
timeFrame: baseline, 1, 2, 4, 8 and 12 weeks
measure: Clinical Global Impression (CGI)
timeFrame: baseline, 1, 2, 4, 8 and the week 12
measure: lipid profiles
timeFrame: baseline, 1, 2, 4, 8 and 12 weeks
Other outcomes:
measure: genetics
timeFrame: baseline
Locations:
city: Tainan
country: Taiwan
facility: Ru-Band Lu
Study officials:
affiliation: National Cheng-Kung University Hospital
name: Ru-Band Lu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.