Combination of Dextromethorphan and Memantine in Treating Bipolar Disorder

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.

Study Overview

• Status: Unknown
• Conditions: Bipolar Disorder II
• Intervention / Treatment: Drug: Memantine; Drug: Dextromethorphan; Drug: dextromethorphan+memantine; Drug: placebo+valproate

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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 30 mg DM; 30mg dextromethorphan+valproate	Drug: Dextromethorphan; Other Names: 30mg dextromethorphan
Experimental: 5 mg MM; 5mg memantine+valproate	Drug: Memantine; Other Names: 5mg memantine+valproate
Experimental: DM+MM; dextromethorphan+memantine+ valproate	Drug: dextromethorphan+memantine
Placebo Comparator: placebo; Placebo+valproate	Drug: placebo+valproate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment change assessed by plasma levels of cytokines (e.g., IL-6, IL-8)	change assessment	baseline, week 1, week 2, week 4, week 8, week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
depression change change	depression change assessed by Hamilton Depression Rating Scale	baseline, week 1, week 2, week 4, week 8, week 12
manic state change	Manic symptom assessed by Young Mania Rating Scale	baseline, week 1, week 2, week 4, week 8, week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
attention function change	attention change assessed by CPT	baseline, week 12
memory change	memory change assessed by WMS	baseline, week 12
executive functioning change	executive function change assessed by WCST	baseline, week 12

Collaborators and Investigators

• Sponsor: National Cheng-Kung University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): December 31, 2016
• Study Completion (Anticipated): December 31, 2017

Study Registration Dates

• First Submitted: August 29, 2014
• First Submitted That Met QC Criteria: January 30, 2017
• First Posted (Estimate): February 1, 2017

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: July 6, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: dextromethorphan; memantine; treatment response
• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; GABA Agents; Anticonvulsants; Antimanic Agents; Respiratory System Agents; Antitussive Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Valproic Acid; Dextromethorphan; Memantine
• Other Study ID Numbers: CombindBP2014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No