NMDA Modulation in Antidepressant Nonresponders With Major Depressive Disorder

Major Depressive Disorder Clinical Trial

Official title:

NMDA Modulation in Antidepressant Nonresponders With Major Depressive Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05136755
• Other study ID #: CMUH110-REC3-123
• Status: Recruiting
• Phase: Phase 2
• Start date: January 25, 2022
• Est. completion date: December 2024

Study information

• Verified date: February 2023
• Source: China Medical University Hospital
• Contact: Hsien-Yuan Lane, M.D., Ph.D
• Phone: 886 4 22052121
• Email: hylane[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Most of the current antidepressants for major depressive disorder (MDD) are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. NMDA hypofunction has been implicated in the pathophysiology of depression. This study aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) in the treatment of antidepressant nonresponders with MDD.

Description:

Major depressive disorder (MDD) is a multi-factorial disorder. Most of the current antidepressants are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. Many patients respond poorly to antidepressants and suffer from side effects. NMDA hypofunction has been implicated in the pathophysiology of depression. MDD is often associated with cognitive deficits which are not necessarily recovered by current antidepressants. The NMDA receptor regulates synaptic plasticity, memory, and cognition. Therefore, this study aims to examine the efficacy and safety as well as cognitive function improvement of NMDAE in the treatment of antidepressant nonresponders with MDD. The investigators will enroll a total of 50 antidepressant nonresponders with MDD. All patients, continuing their originally ongoing treatment throughout the study period, will be randomly assigned into either of two treatment groups: NMDAE or placebo. We will biweekly measure clinical performances using 17-item Hamilton Rating Scale for Depression, Global Assessment of Function, Perceived Stress Scale, Visual Analogue Scale for pain, Clinical Global Impression, and side effects. Quality of life and cognitive functions will be assessed at baseline and at endpoint of treatment. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Have a DSM-5 (American Psychiatric Association) diagnosis of MDD
• Have failed to respond to at least one antidepressant with adequate dosage and treatment duration
• Their original treatments should have been unchanged for at least 8 weeks. Some treatment-resistant patients (that is, having failed to respond to at least two different classes of antidepressants) who have started to refuse any antidepressant by themselves due to previous failure experience are also allowed, if they have already been antidepressant-free for at least 2 weeks
• 17-item Hamilton Rating Scale for Depression total score = 18
• 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
• Bipolar disorder, schizophrenia or other psychotic disorder
• Moderate-severe suicidal risks
• Severe cognitive impairment
• Initiating or stopping formal psychotherapy within six weeks prior to enrollment
• A history of previously received electroconvulsive therapy
• Inability to follow protocol

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Major Depressive Disorder

Intervention

Drug:
• NMDAE
Use of an NMDA enhancer for the treatment of antidepressant nonresponders with MDD
• Placebo Cap
Use of placebo as a comparator

Locations

Country	Name	City	State
Taiwan	Department of Psychiatry, China Medical University Hospital	Taichung

Sponsors (1)

Lead Sponsor	Collaborator
China Medical University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Change in Global Assessment 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
Secondary	Change Change in Perceived Stress Scalein 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	Visual Analogue Scale for pain	Assessment of pain Minimum value: 0, maximum value:10, the higher scores mean a worse outcome.	week 0, 2, 4, 6, 8
Secondary	Clinical Global Impression		week 0, 2, 4, 6, 8
Secondary	Quality of life (SF-36)		week 0, 8
Secondary	Visual Continuous Performance Test	Assessment of sustained attention	week 0, 8
Secondary	Wisconsin Card Sorting Test	Assessment of abstract and shift set	week 0, 8
Secondary	Logical Memory Test of the Wechsler Memory Scale	Assessment of episodic memory	week 0, 8
Secondary	Digit Span	Assessment of verbal working memory	week 0, 8
Secondary	Spatial Span	Assessment of nonverbal working memory	week 0, 8
Secondary	Category Fluency	Assessment of speed of processing	week 0, 8
Secondary	Trail Marking A	Assessment of speed of processing	week 0, 8
Secondary	WAIS-III Digit Symbol-Coding	Assessment of speed of processing	week 0, 8
Secondary	Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) V2.0	Assessment of social cognition	week 0, 8