NCT03043560

Study to Treat Major Depressive Disorder With a New Medication

Developing Neuronal KCNQ Channel Modulators for Mood Disorders

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: James Murrough · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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).

Detailed description

Depressive disorders are among the most disabling medical conditions worldwide and currently available treatments fall short of addressing this large public health burden. Dysfunction within the brain reward system is emerging as a core feature of depressive disorders, in particular related to deficits in motivation, interest, and response to pleasure (e.g., anhedonia: markedly diminished response to pleasure). Evidences from a series of preclinical studies from our group highlighted the KCNQ subtype of neuronal potassium (K+) channel as a novel target for the treatment of depressive disorders and our human pilot study showed a reduction in anhedonia and related symptoms, and an increased brain response to reward (as measured by functional magnetic resonance imaging \[fMRI\]) following treatment with ezogabine. Building on this data, the current project will assess reward circuit activity following treatment with ezogabine in depressed patients with a current depressive disorder (Major depressive disorder \[MDD\], persistent depressive disorder, other specified depressive disorder) and anhedonia (defined by a score ≥ 20 on the Snaith-Hamilton Pleasure Scale \[SHAPS\]), using fMRI to investigate the cortico-striatal circuit to reward. This study represents the first part of the R61/R33 National Institutes of Health (NIH) founded project. A clear increase in reward circuit activation in at least one ezogabine treatment group compared to placebo, given acceptable tolerability, will constitute a "go" and the project will move to the next phase (R33), where we aim to examine the relationship between treatment, reward circuit activity, and behavioral and clinical outcomes in a larger, confirmatory efficacy trial of ezogabine for depression with anhedonia.

Conditions

• Depressive Disorder
• Anhedonia

Interventions

Type	Name	Description
DRUG	Ezogabine	daily for 5 weeks
DRUG	Placebos	placebo pill daily for 5 weeks

Timeline

• Start date: 2017-09-25
• Primary completion: 2019-08-30
• Completion: 2019-08-30
• First posted: 2017-02-06
• Last updated: 2020-10-23
• Results posted: 2020-10-23

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study