NMDA Receptor Modulation for the Treatment of Bipolar I Disorder

NMDA Receptor Modulation for the Treatment of Cognitive Impairment and Perceived Stress in Bipolar I Disorder

At present, the treatment of Bipolar I disorder (BD-I), especially its depressive episode (bipolar depression), is still limited, because there is no effective treatment for the associated cognitive impairment and perceived stress. NMDA receptor (NMDAR) dysfunction is associated with BD-I, particularly its cognitive impairment and perceived stress. This study aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) in the treatment of cognitive impairment and perceived stress in the patients with bipolar depression.

Study Overview

• Status: Recruiting
• Conditions: Bipolar I Disorder
• Intervention / Treatment: Drug: NMDAE; Drug: Placebo Cap

Detailed Description

Bipolar I disorder (BD-I) is a severe brain disorder. At present, the treatment of BD-I, especially its depressive episode (bipolar depression), is still limited, because there is no effective treatment for the associated cognitive impairment and perceived stress. This study aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) in the treatment of cognitive impairment and perceived stress in the patients with bipolar depression.

The subjects are bipolar depression patients. They have been treated for bipolar depression for at least four weeks but remain depressive. Participating in this study, they will continue the original treatment, and will be randomized, double-blindly to receive the NMDAE or placebo for 8 weeks. We will measure 6 cognitive domains (including 9 cognitive tests) and quality of life at weeks 0 and 8; and assess the Perceived Stress Scale, Global Assessment of Function (GAF), various scales for clinical symptoms, and side effects at weeks 0, 2, 4, 6, and 8.

The efficacies of NMDAE and placebo will be compared. Chi-square (or Fisher's exact test) will be used to compare differences of categorical variables and t-test (or Mann-Whitney test if the distribution is not normal) for continuous variables between treatment groups. Mean changes from baseline in repeated-measure assessments will be assessed using the generalized estimating equation (GEE). All p values for clinical measures will be based on two-tailed tests with a significance level of 0.05.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hsien-Yuan Lane Lane, M.D., Ph.D; Phone Number: 1855 886 4 22052121; Email: hylane@gmail.com

Study Locations

• Taiwan
  • Taichung, Taiwan
    • Recruiting
    • Department of Psychiatry, China Medical University Hospital
    • Contact: Hsien-Yuan Lane, M.D., Ph.D; Phone Number: 1855 886 4 22052121; Email: hylane@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Are 18 to 65 years of age;
• Satisfy a DSM-5-TR (American Psychiatric Association) diagnosis of BD-I, current episode depressed, after treatment of stable (i.e., at least 4 weeks) and adequate treatment of antipsychotic (quetiapine or lurasidone) and/or mood stabilizer;
• Have a 17-item Hamilton Depression Rating Scale (HAMD) score ≥18 and a Young Mania Rating Scale (YMRS) score ≤7 at baseline;
• Agree to participate in the study and provide informed consent

Exclusion Criteria:

• Current substance abuse or history of substance dependence in the past 6 months
• History of epilepsy, head trauma, stroke or other serious medical or neurological illness which may interfere with the study
• Schizophrenia or other psychotic disorder
• Moderate-severe suicidal risks
• Severe cognitive impairment
• Clinically significant laboratory screening tests (including blood routine, biochemical tests)
• Pregnancy or lactation;
• Inability to follow protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo Cap; Use of placebo as a comparator.
Experimental: NMDAE; An NMDA enhancer	Drug: NMDAE; Use of an NMDA enhancer for the treatment of bipolar depression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digit Span	Assessment of verbal working memory	week 0, 8
Spatial Span	Assessment of nonverbal working memory	week 0, 8
Category Fluency	Assessment of speed of processing	week 0, 8
Trail Marking A	Assessment of speed of processing	week 0, 8
WAIS-III Digit Symbol-Coding	Assessment of speed of processing	week 0, 8
Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) V2.0	Assessment of social cognition	week 0, 8
Change in Visual Continuous Performance Test	Assessment of sustained attention	week 0, 8
Change in Wisconsin Card Sorting Test	Assessment of abstract and shift set	week 0, 8
Change in Logical Memory Test of the Wechsler Memory Scale	Assessment of episodic memory	week 0, 8
Change in Perceived Stress Scale in Perceived Stress Scale	Assessment of stress and anxiety symptoms Minimum value: 0, maximum value:56, the higher scores mean a worse outcome.	week 0, 2, 4, 6, 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quality of life (SF-36)		week 0, 8
Change in Global Assessmeint of Functioning	Assessment of global improvement. Minimum value: 1, maximum value:100, the higher scores mean a better outcome.	Week 0, 2, 4, 6, 8
Change in Hamilton Rating Scale for Depression	Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.	Week 0, 2, 4, 6, 8
Change in Montgomery-Åsberg Depression Rating Scale	Assessment of depressive symptoms. Minimum value: 0, maximum value:60, the higher scores mean a worse outcome.	Week 0, 2, 4, 6, 8
Change in Young Mania Rating Scale	Assessment of manic symptoms. Minimum value: 0, maximum value:60, the higher scores mean a worse outcome.	Week 0, 2, 4, 6, 8
Change in Beck Scale for Suicide Ideation	Assessment of Suicide Ideation. Minimum value: 0, maximum value:38, the higher scores mean a greater risk of suicide.	Week 0, 2, 4, 6, 8
Change in Clinical Global Impression Scale		Week 0, 2, 4, 6, 8

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Collaborators: National Science and Technology Council

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 28, 2023
• First Submitted That Met QC Criteria: August 3, 2023
• First Posted (Actual): August 4, 2023

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Bipolar depression; Bipolar I disorder; NMDA
• Other Study ID Numbers: CMUH111-REC2-222

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No