Depressive DisorderPhase 2NCT03043560

Study to Treat Major Depressive Disorder With a New Medication

A Phase 2 study testing Ezogabine in people with Depressive Disorder and Anhedonia, run by James Murrough at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Depressive Disorder, Anhedonia
What is being tested?: Ezogabine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 45 participants
Where: 2 sitesUnited States
Study dates: 25 Sep 2017to 30 Aug 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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;

Show all 18Show fewer

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:
Subjects with a positive urine drug screen for cannabinoids, barbiturates, opiates, amphetamines, or benzodiazepines may be allowed in the study provided that the drug was used for a documented, legitimate medical purpose and/or the use of such products may be discontinued (documented by a negative repeat test) prior to randomization;
Medically appropriate episodic use (up to 3 days) of narcotic analgesics for acute medical indications is allowed (Discussion with PI required)
Potential participants will not be discontinued from medication for the purposes of this study. If a patient is taking a protocol dis-allowed medication at the time of screening, the patient may discontinue the medication under the supervision of the treating physician in the case that the patient is not benefiting from the medication or otherwise wishes to discontinue the medication. In no case will a dis-allowed medication be discontinued for the purpose of study participation if the patient is receiving clinical benefit from the medication.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Baylor College of Medicine
Houston, Texas, 77030
Icahn School of Medicine at Mount Sinai
New York, New York, 10029

Other trials in United States

About this study

Official title: Developing Neuronal KCNQ Channel Modulators for Mood Disorders

Read the 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
Being tested: Ezogabine, Placebos
Keywords: depression, anhedonia, reward
Medical subject headings: Depressive Disorder, Anhedonia, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EzogabineDrug
Also called Potiga
daily for 5 weeks
PlacebosDrug
placebo pill daily for 5 weeks

Study groups in NCT03043560
Study group	Role	What they receive
Ezogabine	Experimental	Participants will receive treatment with ezogabine up to 900mg/day. Receives: Drug: Ezogabine
Placebo	Placebo comparator	Participants will receive treatment with a matching placebo pill. Receives: Drug: Placebos

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: baseline and 5 weeks

Secondary outcomes (8)

Change in Snaith-Hamilton Pleasure Scale (SHAPS)
The SHAPS is a well-validated 14-item self-report questionnaire commonly used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater pleasure capacity. A total score can be derived by summing the responses to each item. Items answered with "strongly agree" are coded as "1", while a "strongly disagree" response was assigned a score of "4." Total scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.
Measured: baseline and 5 weeks
Clinical Global Impression - Improvement (CGI-I)
A widely administered clinician rated global measure of the degree of improvement from the initial assessment in subject overall illness severity. 7 point scale rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Measured: baseline and 5 weeks
Clinical Global Impression - Severity (CGI-S)
Clinician rated global measure of subject overall illness severity. a 7-point scale rated as 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
Measured: baseline and 5 weeks
Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS)
A measure specifically designed to assess hedonic capacity for social and interpersonal pleasure.The ACIPS is a 17-item self-report measure scored on a likert scale, ranging from 1 (very false for me) to 6 (very true for me). Full scale from 17-102, higher score indicates higher hedonic capacity
Measured: baseline and 5 weeks
Montgomery-Asberg Depression Rating Scale (MADRS)
A 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).
Measured: baseline and 5 weeks
World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)
A 12-item generic assessment instrument that measures the level of functioning. Each item is scored from 0 to 4 and the items are summed to provide a total score. The score therefore ranges from 0 to 48, with higher scores indicating greater disability.
Measured: baseline and 5 weeks
Temporal Experience of Pleasure Scale (TEPS)
The TEPS is composed of 18-items rated on a likert-type scale ranging from 1 (Very True for me) to 6 (Very False for me), and yields two subscales. Ten items make up the TEPS-Anticipatory Pleasure (TEPS-ANT) scale with a range from 10 (not motivated) to 60 (highly motivated). The other eight TEPS items make up the TEPS-Consummatory Pleasure (TEPS-CON) scale; range from 8 (not responsive) to 48 (highly responsive). Total scores range is 18-108. Lower scores indicate greater levels of anhedonia.
Measured: baseline and 5 weeks
Specific Loss of Interest and Pleasure Scale (SLIPS)
The SLIPS is a recently developed and validated measure of anhedonia that is tailored to detect recent changes in anhedonia. A 23-item measure, each item range from 0-3. Full scale from 0 to 69, higher score indicates more recent changes.
Measured: baseline 5 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Sep 201730 Aug 2019

First posted6 Feb 2017 (estimated)
Study start25 Sep 2017
Primary completion30 Aug 2019
Study completion30 Aug 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Depressive DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 45 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03043560
Sponsor's protocol ID: GCO 16-0374
Other IDs: 1R61MH111932-01
Status last verified: Sep 2020
First submitted: 2 Feb 2017
Last updated: 23 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Data from this study may be submitted to the National Database for Clinical Research Related to Mental Illness (NDCT). NDCT isa data repository run by the National Institute of Mental Health (NIMH) that allows researchers studying mental illness to collect and share deidentified information with each other. During and after the study, the researchers will send deidentified information about health and behavior and in some cases, genetic information, to NDCT. Other researchers nationwide can then file an application with the NIMH to obtain access to deidentified study data for research purposes.

Publications

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.
PubMed 33653118

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 23 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Developing Neuronal KCNQ Channel Modulators for Mood Disorders
ClinicalTrials.gov ID: NCT03043560
Acronym / sponsor ID: GCO 16-0374
Conditions: Depressive Disorder, Anhedonia
Keywords: depression, anhedonia, reward
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 45 participants (actual)
Lead sponsor: James MurroughUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH), Baylor College of Medicine
Study start: 25 Sep 2017 (actual)
Primary completion: 30 Aug 2019 (actual)
Study completion: 30 Aug 2019 (actual)
First posted: 6 Feb 2017 (estimated)
Results: Posted 23 Oct 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Ezogabine	Experimental	Drug: EzogabineParticipants will receive treatment with ezogabine up to 900mg/day.
Placebo	Placebo comparator	Drug: PlacebosParticipants will receive treatment with a matching placebo pill.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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;

Key exclusion criteria (18 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EzogabineAlso: Potigadaily for 5 weeks	Drug	Ezogabine
Placebosplacebo pill daily for 5 weeks	Drug	Placebo

Primary outcome

Change in Ventral Striatum (VS) Activation
Time frame: baseline and 5 weeks
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.

8 secondary outcomes

Change in Snaith-Hamilton Pleasure Scale (SHAPS)
Time frame: baseline and 5 weeks
Clinical Global Impression - Improvement (CGI-I)
Time frame: baseline and 5 weeks
Clinical Global Impression - Severity (CGI-S)
Time frame: baseline and 5 weeks
Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS)
Time frame: baseline and 5 weeks
Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: baseline and 5 weeks
World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)
Time frame: baseline and 5 weeks
Temporal Experience of Pleasure Scale (TEPS)
Time frame: baseline and 5 weeks
Specific Loss of Interest and Pleasure Scale (SLIPS)
Time frame: baseline 5 weeks

Results and safety

Results posted to the registry on 23 Oct 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ezogabine	21	20
Placebo	24	21

Primary outcome: Change in Ventral Striatum (VS) Activation

Time frame: baseline and 5 weeks. Mean (Standard Deviation). Unit: Bold Oxygen-level Dependent (BOLD) Signa

Measure	Ezogabine n = 21	Placebo n = 24
baseline	-0.26 (0.69)	0.95 (0.79)
5 weeks	0.176 (0.81)	0.015 (0.68)

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: 8 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ezogabine	0 of 21 (0%)	21 of 21 (100%)	0 of 21
Placebo	0 of 24 (0%)	19 of 24 (79.2%)	0 of 24

Limitations and caveats (from the sponsor): The relatively small sample size and termination of enrollment prior to the planned target limit conclusions regarding efficacy and generalizability.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33653118Costi 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.
Individual participant dataSharing planned: Yes. Data from this study may be submitted to the National Database for Clinical Research Related to Mental Illness (NDCT). NDCT isa data repository run by the National Institute of Mental Health (NIMH) that allows researchers studying mental illness to collect and share deidentified information with each other. During and after the study, the researchers will send deidentified information about health and behavior and in some cases, genetic information, to NDCT. Other researchers nationwide can then file an application with the NIMH to obtain access to deidentified study data for research purposes.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

James Murrough, MD, PhD principal investigator

Icahn School of Medicine at Mount Sinai

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ezogabine in people with Depressive Disorder and Anhedonia, run by James Murrough at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Ventral Striatum (VS) Activation (time frame: baseline and 5 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03043560, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2020.