NMDA Modulation in Antidepressant Nonresponders With Major Depressive Disorder

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.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo Cap; Drug: NMDAE

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hsien-Yuan 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: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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 antidepressant nonresponders with MDD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression		week 0, 2, 4, 6, 8
Quality of life (SF-36)		week 0, 8
Visual Continuous Performance Test	Assessment of sustained attention	week 0, 8
Wisconsin Card Sorting Test	Assessment of abstract and shift set	week 0, 8
Logical Memory Test of the Wechsler Memory Scale	Assessment of episodic memory	week 0, 8
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 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
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

Collaborators and Investigators

• Sponsor: China Medical University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2022
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (Actual): November 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 16, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Major depressive disorder; NMDA; Antidepressant nonresponders
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: CMUH110-REC3-123

Drug and device information, study documents

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