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NMDA Modulation in Major Depressive Disorder

Phase 2
Recruiting
Conditions
Major Depressive Disorder
Interventions
Drug: NMDAE
Drug: Placebo Cap
Registration Number
NCT04637620
Lead Sponsor
China Medical University Hospital
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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
90
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NMDAENMDAEAn NMDA enhancer
PlaceboPlacebo CapPlacebo
SSRISertralineSertraline (selective serotonin reuptake inhibitor)
Primary Outcome Measures
NameTimeMethod
Change in Global Assessment of FunctioningWeek 0, 2, 4, 6, 8

Assessment of global improvement. Minimum value: 1, maximum value:100, the higher scores mean a better outcome.

Change in Hamilton Rating Scale for Depressionweek 0, 2, 4, 6, 8

Assessment of depressive symptoms Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.

Secondary Outcome Measures
NameTimeMethod
Wisconsin Card Sorting Testweek 0, 8

Assessment of abstract and shift set

Category Fluencyweek 0, 8

Assessment of speed of processing

Trail Marking Aweek 0, 8

Assessment of speed of processing

WAIS-III Digit Symbol-Codingweek 0, 8

Assessment of speed of processing

Visual Continuous Performance Testweek 0, 8

Assessment of sustained attention

Change in Perceived Stress Scaleweek 0, 2, 4, 6, 8

Assessment of stress and anxiety symptoms Minimum value: 0, maximum value:56, the higher scores mean a worse outcome.

Clinical Global Impressionweek 0, 2, 4, 6, 8
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.

Digit Spanweek 0, 8

Assessment of verbal working memory

Spatial Spanweek 0, 8

Assessment of nonverbal working memory

Quality of life (SF-36)week 0, 8
Logical Memory Test of the Wechsler Memory Scaleweek 0, 8

Assessment of episodic memory

Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) V2.0week 0, 8

Assessment of social cognition

Trial Locations

Locations (1)

Department of Psychiatry, China Medical University Hospital

🇨🇳

Taichung, Taiwan

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