NMDA Modulation in 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. Therefore, this study will examine the efficacy and safety as well as cognitive function improvement of an NMDA enhancer (NMDAE) in the treatment of MDD in the adults.

Study Overview

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

Detailed Description

Major depressive disorder (MDD) is a complex and multi-factorial disorder. Most of the current antidepressants are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. Many patients have significant side effects after treatment with antidepressants which hamper the motivation for treatment and medication adherence. 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. In our previous studies, cognitive improvement has been observed with treatment of NMDA enhancers. Therefore, this study will examine the efficacy and safety as well as cognitive function improvement of NMDAE in the treatment of MDD in the general adults by comparing with sertraline (a selective serotonin reuptake inhibitor [SSRI]) and placebo. The investigators will enroll non-elderly adult patients with MDD for an 8-week treatment. All patients will be randomly assigned into three groups: NMDAE, sertraline, or placebo. The investigators will biweekly measure clinical performances and side effects. Cognitive functions will be assessed at baseline and at endpoint of treatment by a battery of tests. The efficacy of three groups will be compared.

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

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan
    • Recruiting
    • Department of Psychiatry, China Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have a DSM-5 (American Psychiatric Association) diagnosis of MDD
• 17-item Hamilton Rating Scale for Depression total score ≥ 18
• Free of antidepressant drugs for at least 2 weeks
• 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 depression, 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 severe adverse reaction to SSRIs
• A treatment-resistant history (that is, they have failed to respond to two or more different classes of antidepressants with adequate dosage and treatment duration
• 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
• Masking: TRIPLE

Number of Arms

3

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 MDD
ACTIVE_COMPARATOR: SSRI; Sertraline (selective serotonin reuptake inhibitor)	Drug: Sertraline; Use of SSRI as an active comparator

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
Change 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
Visual Analogue Scale (VAS)	Assessment of pain Minimum value: 0, maximum value:10, the higher scores mean a worse outcome.	week 0, 2, 4, 6, 8
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

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Collaborators: Ministry of Science and Technology, Taiwan

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2017
• Primary Completion (ANTICIPATED): September 1, 2024
• Study Completion (ANTICIPATED): December 1, 2024

Study Registration Dates

• First Submitted: October 11, 2020
• First Submitted That Met QC Criteria: November 15, 2020
• First Posted (ACTUAL): November 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Major depressive disorder; Selective serotonin reuptake inhibitor; NMDA
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Sertraline
• Other Study ID Numbers: CMUH103-REC2-130

Drug and device information, study documents

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