Clinical trial NCT03039842: Combination of Dextromethorphan and Memantine in Treating Bipolar Disorder
Official title: Combination of Dextromethorphan and Memantine in Treating Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Bipolar Disorder II
Keywords: dextromethorphan; memantine; treatment response
Lead sponsor: National Cheng-Kung University Hospital
Sponsor class: OTHER
First posted: 2017-02-01
Enrollment: 300
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: This is a research clinical trial of double-blind, stratified randomized, parallel group, two-centre study. It will be conducted in a total of 250\~300 male and female subjects from the Department of Psychiatry at National Cheng Kung University Hospital. Eligible subjects will be psychiatric out- and in-patients, aged between 18\~65 years old, who have psychiatric evaluation with clinically suspected of having bipolar II disorder and fulfill the inclusion and exclusion criteria. The add-on double-blind study treatment with dextromethorphan/place will commence at randomization for while patients continue open-label valproate. Subjects will be enrolled for 12 weeks double-blind add-on treatment and randomly assigned to (1) 30mg dextromethorphan+valproate, (2) 5mg memantine+valproate, (3) dextromethorphan+memantine+valproate or (4) placebo+valproate. Concomitant benzodiazepine medication (preferably up to 8mg lorazepam) may be used for daytime sedation, agitation or insomnia during the study. For the consideration of the less influence to immune-system, resperidone 1-3mg/daily and fluoxetine maximum 20mg/daily will be chose. We will measure the treatment response and side effect to clarify the curative effect of DM and memantine add-on therapy to valproate in the treatment of bipolar disorders. This study is being performed to investigate the possibly significant beneficial effects on the subtypes of bipolar disorders psychopathology.

Detailed description: A total of 250\~300 male and female subjects from the Department of Psychiatry at National Cheng Kung University Hospital. Eligible subjects who are aged between 18\~65 years old and clinically suspected of having bipolar II disorder are invited. The add-on double-blind study treatment with dextromethorphan/place will commence at randomization for while patients continue open-label valproate. Subjects will be enrolled for 12 weeks double-blind add-on treatment and randomly assigned to (1) 30mg dextromethorphan+valproate, (2) 5mg memantine+valproate, (3) dextromethorphan+memantine+valproate or (4) placebo+valproate. Concomitant benzodiazepine medication (preferably up to 8mg lorazepam) may be used for daytime sedation, agitation or insomnia during the study. For the consideration of the less influence to immune-system, resperidone 1-3mg/daily and fluoxetine maximum 20mg/daily will be chose. We will measure the treatment response and side effect to clarify the curative effect of DM and memantine add-on therapy to valproate in the treatment of bipolar disorders. This study is being performed to investigate the possibly significant beneficial effects on the subtypes of bipolar disorders psychopathology.

Eligibility criteria: Inclusion Criteria:

* A 2-day minimum for hypomania to diagnose bipolar II disorder
* A total of Hamilton Rating Scale for Depression scored at least 18 or Young Mania Rating Scale scored at least 14 at the screening stage
* Must allow to ensure acceptable compliance and visit

Exclusion Criteria:

* Pregnant females or nursing
* Women of childbearing potential not using adequate contraception
* Received dextromethorphan, memantine, other antiinflammatory medication within 1 week prior
* Clinically significant medical condition (cardiac, hepatic and renal disease)
* Received electroconvulsive therapy patients within 4 weeks prior to the first dose of double-blind medication
* Increase in total SGOT, SGPT, BUN and creatinine by more than 3X upper limit of normal.

Primary outcomes:
measure: treatment change assessed by plasma levels of cytokines (e.g., IL-6, IL-8)
timeFrame: baseline, week 1, week 2, week 4, week 8, week 12
Secondary outcomes:
measure: depression change change
timeFrame: baseline, week 1, week 2, week 4, week 8, week 12
measure: manic state change
timeFrame: baseline, week 1, week 2, week 4, week 8, week 12
Other outcomes:
measure: attention function change
timeFrame: baseline, week 12
measure: memory change
timeFrame: baseline, week 12
measure: executive functioning change
timeFrame: baseline, week 12
Locations:
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
Study officials:
affiliation: Department of Psychiatry, National Cheng Kung University
name: Ru-Band Lu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee SY, Wang TY, Chen SL, Chang YH, Chen PS, Huang SY, Tzeng NS, Wang LJ, Lee IH, Chen KC, Yang YK, Hong JS, Lu RB. Combination of dextromethorphan and memantine in treating bipolar spectrum disorder: a 12-week double-blind randomized clinical trial. Int J Bipolar Disord. 2020 Mar 2;8(1):11. doi: 10.1186/s40345-019-0174-8.