Study to Treat Major Depressive Disorder With a New Medication

NCT03043560 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GCO 16-03741R61MH111932-01
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

This project is designed to examine the neuronal KCNQ2/3 potassium (K+) channel subtype as a novel treatment target for mood disorders through the administration of the KCNQ-selective channel opener ezogabine (Potiga, GlaxoSmithKline; FDA-approved for the treatment of seizure disorders).

Conditions

Depressive Disorder; Anhedonia

Keywords

depression; anhedonia; reward

Outcome Measures

Primary Outcomes (1)

• Change in Ventral Striatum (VS) Activation

  change in activation during reward anticipation within the bilateral VS from baseline (Study Visit 0) to the primary outcome visit (Study Visit 5) as measured by functional MRI during the incentive flanker task (IFT). The IFT, like the Monetary Incentive Delay task, permits discrete modeling of brain activity during anticipation of an incentive. Functional scans were preprocessed and denoised for motion and physiological noise using multi-echo independent component analysis (ME-ICA). Task-based modeling was conducted using AFNI and FSL software. The primary outcome for reward anticipation was the contrast of reward cue compared to neutral cue (reward\>neutral cue). The primary imaging outcome was analyzed using a linear mixed model with a single random intercept term treating time as discrete or continuous as appropriate.

  baseline and 5 weeks

Secondary Outcomes (8)

• Change in Snaith-Hamilton Pleasure Scale (SHAPS)

  baseline and 5 weeks

• Clinical Global Impression - Improvement (CGI-I)

  baseline and 5 weeks

• Clinical Global Impression - Severity (CGI-S)

  baseline and 5 weeks

• Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS)

  baseline and 5 weeks

• Montgomery-Asberg Depression Rating Scale (MADRS)

  baseline and 5 weeks

Study Arms (2)

Ezogabine

EXPERIMENTAL

Participants will receive treatment with ezogabine up to 900mg/day.

Drug: Ezogabine

Placebo

PLACEBO COMPARATOR

Participants will receive treatment with a matching placebo pill.

Drug: Placebos

Interventions

Ezogabine DRUG

daily for 5 weeks

Also known as: Potiga

Ezogabine

Placebos DRUG

placebo pill daily for 5 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study;
• Men and women, age 18-65;
• Participants must meet DSM-V criteria for current depressive disorder (major depressive disorder \[MDD\], persistent depressive disorder, other specified depressive disorder) as determined by a study psychiatrist and confirmed using the Structured Clinical Interview for DSM-V (SCID);
• Clinically significant anhedonia as determined by a SHAPS score ≥ 20 at screening;
• Current illness severity is at least moderate, defined as a score of ≥4 on the Clinical Global Impression-Severity (CGI-S) Scale;
• If female of childbearing potential, must agree to use of a medically accepted form of contraception, or else agree to abstinence.

You may not qualify if:

• A primary psychiatric diagnosis other than a depressive disorder as defined by DSM-V \[co-morbid anxiety disorders (including agoraphobia, generalized anxiety disorder, social anxiety disorder and panic disorder) and Posttraumatic Stress Disorder (PTSD) are allowed\] or major cognitive disorder;
• Meets criteria for a substance or alcohol use disorder in the past 6 months;
• Female participants who are pregnant, breastfeeding, or may become pregnant, or unwilling to practice birth control during participation in the study;
• Positive urine toxicology screen for drugs of abuse at the time of screening;
• Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease;
• Clinically significant abnormalities of laboratory tests, physical examination, or ECG;
• Prolonged QT Interval at screening, operationalized as a QTc of \> 480 ms;
• A history of retinal abnormalities (i.e., pigment changes, retinal dystrophy) or findings of retinal pathology on ophthalmological exam at baseline;
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data;
• Use of any dis-allowed medication according to the study protocol;
• Serious and imminent risk of self harm or violence as determined by the PI;
• Extreme illness severity as defined by a GCI-S score \>6;
• Any contraindication to MRI including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more;
• History of non-response to electroconvulsive therapy in the current depressive episode
• Exceptions:

Sponsors & Collaborators

• James Murrough: lead
• National Institute of Mental Health (NIMH): collaborator
• Baylor College of Medicine: collaborator

Study Sites (2)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Costi S, Morris LS, Kirkwood KA, Hoch M, Corniquel M, Vo-Le B, Iqbal T, Chadha N, Pizzagalli DA, Whitton A, Bevilacqua L, Jha MK, Ursu S, Swann AC, Collins KA, Salas R, Bagiella E, Parides MK, Stern ER, Iosifescu DV, Han MH, Mathew SJ, Murrough JW. Impact of the KCNQ2/3 Channel Opener Ezogabine on Reward Circuit Activity and Clinical Symptoms in Depression: Results From a Randomized Controlled Trial. Am J Psychiatry. 2021 May 1;178(5):437-446. doi: 10.1176/appi.ajp.2020.20050653. Epub 2021 Mar 3.

  PMID: 33653118 DERIVED

MeSH Terms

Conditions

Depressive Disorder; Anhedonia; Depression

Interventions

ezogabine

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Limitations and Caveats

The relatively small sample size and termination of enrollment prior to the planned target limit conclusions regarding efficacy and generalizability.

Results Point of Contact

• Title: Dr, James Murrough
• Organization: Icahn School of Medicine at Mount Sinai

james.murrough@mssm.edu

212-585-4640

Study Officials

• James Murrough, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 2, 2017
• First Posted: February 6, 2017
• Study Start: September 25, 2017
• Primary Completion: August 30, 2019
• Study Completion: August 30, 2019
• Last Updated: October 23, 2020
• Results First Posted: October 23, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

US (2)