Clinical trial NCT05977023: NMDA Receptor Modulation for the Treatment of Bipolar I Disorder
Official title: NMDA Receptor Modulation for the Treatment of Cognitive Impairment and Perceived Stress in Bipolar I Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Bipolar I Disorder
Keywords: Bipolar I disorder
Bipolar depression
NMDA
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
Collaborators: name: National Science and Technology Council
First posted: 2023-08-04
Enrollment: 90
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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Visual Continuous Performance Test
timeFrame: week 0, 8
measure: Change in Wisconsin Card Sorting Test
timeFrame: week 0, 8
measure: Change in Logical Memory Test of the Wechsler Memory Scale
timeFrame: week 0, 8
measure: Digit Span
timeFrame: week 0, 8
measure: Spatial Span
timeFrame: week 0, 8
measure: Category Fluency
timeFrame: week 0, 8
measure: Trail Marking A
timeFrame: week 0, 8
measure: WAIS-III Digit Symbol-Coding
timeFrame: week 0, 8
measure: Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) V2.0
timeFrame: week 0, 8
measure: Change in Perceived Stress Scale in Perceived Stress Scale
timeFrame: week 0, 2, 4, 6, 8
Secondary outcomes:
measure: Change in Quality of life (SF-36)
timeFrame: week 0, 8
measure: Change in Global Assessmeint of Functioning
timeFrame: Week 0, 2, 4, 6, 8
measure: Change in Hamilton Rating Scale for Depression
timeFrame: Week 0, 2, 4, 6, 8
measure: Change in Montgomery-Åsberg Depression Rating Scale
timeFrame: Week 0, 2, 4, 6, 8
measure: Change in Young Mania Rating Scale
timeFrame: Week 0, 2, 4, 6, 8
measure: Change in Beck Scale for Suicide Ideation
timeFrame: Week 0, 2, 4, 6, 8
measure: Change in Clinical Global Impression Scale
timeFrame: Week 0, 2, 4, 6, 8
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Department of Psychiatry, China Medical University Hospital
Study officials:
References: