NMDA Modulation in Major Depressive Disorder in Late- Life

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 elderly 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 in the elderly 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 elderly by comparing with sertraline (a selective serotonin reuptake inhibitor [SSRI]) and placebo.

The investigator will enroll elderly patients with MDD for an 8-week treatment. All patients will be randomly assigned into three groups: NMDAE, sertraline, or placebo. The investigator will biweekly measure clinical performances. Cognitive functions will be assessed at baseline and at endpoint of treatment by a battery of tests. The investigator hypothesize that NMDAE can safely yield better efficacy than placebo and sertraline for elderly patients with MDD.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: Sertraline; Drug: NMDA; Drug: Placebo - Cap

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan, 886
    • Chang Gung Memorial Hospital
  • Taichung, Taiwan, 404
    • China Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have a DSM-IV (American Psychiatric Association 1994) diagnosis of MDD
• 17-item Hamilton Rating Scale for Depression total score ≥ 18
• Free of psychotropic drugs for at least 2 weeks
• Have a Mini-Mental State Examination (Folstein, Folstein et al. 1975) score ≥ 20

Exclusion Criteria:

• Current substance abuse or history of substance dependence in the past 6 months
• Use of depot antipsychotics in the past 6 months
• History of epilepsy, head trauma, stroke or other serious medical or neurological illness
• 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 poor response to SSRIs or other antidepressants
• A history of previously received electroconvulsive therapy
• A history of severe adverse reaction to SSRIs or other antidepressants
• Inability to follow protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

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: NMDA; Use of an NMDA enhancer for the treatment of MDD in late life; Other Names: NMDAE
ACTIVE_COMPARATOR: SSRI; Sertraline	Drug: Sertraline; Use of SSRI as an active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of 17-item Hamilton Rating Scale for Depression	Assessment of depressive symptoms. The 17-item Hamilton Rating Scale for Depression will be measured biweekly.	Week 0, 2, 4, 6, 8
Change from baseline of Perceived Stress Scale	Assessment of stress and anxiety symptoms. The Perceived Stress Scale will be measured biweekly	Week 0, 2, 4, 6, 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drop out rate	The rate of drop out	Week 0, 2, 4, 6, 8
Change from baseline of Geriatric Depression Scale	Assessment of geriatric depressive symptoms. The Geriatric Depression Scale will be measured biweekly	Week 0, 2, 4, 6, 8
Clinical Global Impression	Assessment of global improvement	Week 2, 4, 6, 8
Cognitive function	A battery of tests to assess the cognitive function including speed of processing (category fluency) and verbal and nonverbal working memory	Week 0, 8
Change from baseline of Beck's Suicide Scale	Assessment of suicidal symptoms. The Beck's Suicide Scale will be measured biweekly	Week 0, 2, 4, 6, 8

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Publications and helpful links

General Publications

• Lin CH, Wang SH, Lane HY. Effects of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, on Perceived Stress and Cognitive Function Among Patients With Late-Life Depression: A Randomized, Double-Blind, Sertraline- and Placebo-Controlled Trial. Int J Neuropsychopharmacol. 2022 Aug 4;25(7):545-555. doi: 10.1093/ijnp/pyac006.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2016
• Primary Completion (ACTUAL): November 1, 2020
• Study Completion (ACTUAL): November 1, 2020

Study Registration Dates

• First Submitted: January 16, 2018
• First Submitted That Met QC Criteria: January 23, 2018
• First Posted (ACTUAL): January 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 1, 2020
• Last Update Submitted That Met QC Criteria: November 29, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; 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: 101-0365A3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No