NMDA Modulation in Major Depressive Disorder

Sponsor

China Medical University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04637620

Collaborator

Ministry of Science and Technology, Taiwan (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: NMDAE Drug: Sertraline Drug: Placebo Cap	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

NMDA Modulation in Major Depressive Disorder

Actual Study Start Date :

Jun 1, 2017

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
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
Placebo Comparator: Placebo Placebo	Drug: Placebo Cap Use of placebo as a comparator

Arm

Intervention/Treatment

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

Placebo Comparator: Placebo

Placebo

Drug: Placebo Cap

Use of placebo as a comparator

Outcome Measures

Primary Outcome Measures

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 Global Assessment 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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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