NMDA Receptor Modulation for the Treatment of Bipolar I Disorder

Phase 2

Recruiting

• Conditions: Bipolar I Disorder
• Interventions: Drug: NMDAE; Drug: Placebo Cap

• Registration Number: NCT05977023
• Lead Sponsor: China Medical University Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2023-07-28
• Study First Submitted QC: 2023-08-03
• Study First Posted: 2023-08-04
• Status Verified: 2023-10
• Study Start: 2023-10-04
• Last Update Submitted: 2023-10-05
• Last Update Posted: 2023-10-06
• Primary Completion: 2027-11
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NMDAE	NMDAE	An NMDA enhancer
Placebo	Placebo Cap	Placebo

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of Psychiatry, China Medical University Hospital; 🇨🇳 Taichung, Taiwan