Major Depressive DisorderPhase 2NCT02149836
Study to Treat Major Depressive Disorder (MDD) With a New Medication
A Phase 2 study testing ezogabine in people with Major Depressive Disorder and Depression, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
The purpose of this study is to test the antidepressant effects of Ezogabine in major depressive disorder (MDD). The investigators also aim to determine the safety and tolerability Ezogabine in patients with MDD. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder, Depression
- What is being tested?
- ezogabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to Dec 2016
- 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
- Male or female participants, 18-65 years of age;
- Current diagnosis of major depressive disorder according as determined by a psychiatrist and confirmed with The Mini-International Neuropsychiatric Interview (MINI);
- At least moderate depression severity as defined by a score of >= 21 on the Montgomery-Asberg Depression Rating Scale (MADRS);
- At least a moderate level of anhedonia based on a Snaith-Hamilton Pleasure Scale (SHAPS) score ≥ 20;
- If female of childbearing potential, must agree to use of a medically accepted form of contraception, or else agree to abstinent;
- Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.
Who cannot join
- Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, obsessive compulsive disorder or pervasive developmental disorders or mental retardation;
- Diagnosis of a substance use disorder within the past 6 months (excluding substance use disorder in sustained remission)
- Female participants who are pregnant, nursing, for may become pregnant;
- Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
- Clinically significant abnormalities of laboratories, physical examination, or ECG;
- Prolonged QT Interval at screening, operationalized as a QTc of > 480 ms at baseline;
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- Hypokalemia (potassium value less than 3.5mEq/L) or hypomagnesemia (magnesium value less than 1.6mEq/L) at baseline;
- A history of retinal abnormalities (ie, pigment changes, retinal dystrophy) or findings of retinal pathology on ophthalmological exam at baseline
- Antidepressant medication within 2 weeks of start of treatment (4 weeks for fluoxetine)*
- Other psychotropic medication, including antipsychotics and mood stabilizers within 2 weeks of start of treatment; subjects will be allowed to remain on a stable dose of zolpidem 10 mg nightly for sleep or a benzodiazepine as needed for sleep or anxiety (dosage equivalent to lorazepam 1 mg daily or less)
- No current or recent significantly elevated risk of self-harm or violence as determined by the PI.
- For subjects who may participate in the MRI portion of the study, 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: A Proof-Of-Concept Clinical Trial of a Novel KCNQ Potentiator in Major Depressive Disorder
The purpose of this study is to test the antidepressant effects of Ezogabine in major depressive disorder (MDD). The investigators also aim to determine the safety and tolerability Ezogabine in patients with MDD. The investigators hypothesize that depressive symptoms will be significantly decreased following an 8-week treatment period of the medication compared to baseline.
Read the detailed description
Study Introduction:
Major depressive disorder (MDD) is a global health disease associated with significant morbidity and costs. Many anti-depressants exist within the monoaminergic system yet novel therapeutics are still needed outside of this system. Ezogabine, currently approved by the FDA for adjunctive treatment of partial-onset seizures, may serve as a potential key agent for those with MDD. Ezogabine is known to bind to and activate KCNQ transmembrane K+ ion channels, specifically targeting KCNQ2 in the VTA. Such membrane activity has been show to play a role in previous studies involving a social defeat model of depression. Specifically, data has shown that KCNQ channels were upregulated only in resilient mice and moreover, ezogabine was able to potentiate KCNQ channel activity to result in a fast reversal of the depressed phenotype.
General Investigational Plan:
Objectives:
- Primary Efficacy Objective: To test the antidepressant effects of Ezogabine in MDD.
- Primary Safety Objective: To characterize the safety and tolerability of Ezogabine in patients with MDD.
- Secondary Objectives: To measure the effects of Ezogabine on ventral tegmental area (VTA)-striatal reward circuitry in MDD using reward task-based functional MRI. Rationale: Ezogabine is hypothesized to modulate the firing rate of VTA dopamine (DA) neurons and thereby influence the functioning of the mesolimbic reward system.
Hypotheses
- Efficacy Hypothesis:
Hypothesis 1a: Depressive symptoms will be significantly decreased following an 8-week treatment period compared to baseline, as measured by change in Montgomery-Åsberg Depression Rating Scale (MADRS).
Hypothesis 1b: The antidepressant response rate at study end (defined as 50% in depressive symptoms compared to baseline) will exceed 50%, consistent with known response rates of current antidepressant agents.
- Safety Hypothesis: Ezogabine will be safe and adverse event rates will be similar to rates observed in other adult populations. Specific safety items to be monitored include frequency and intensity of adverse events as measured by the Patient Rated Inventory of Side Effects (PRISE) and treatment-emergent suicidal ideation or behavior as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS).
- Conditions
- Major Depressive Disorder, Depression
- Being tested
- ezogabine
- Keywords
- major depressive disorder, depression, treatment resistent depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ezogabineDrug
Also called Potiga, Retigabine
Treatment Week 1: 100mg of Ezogabine by mouth three times per day (total daily dose = 300mg) Treatment Week 2: dose will be increased to 150 mg Ezogabine by mouth three times per day (total daily dose = 450mg).
Treatment Week 3: dose will be increased to 200mg of Ezogabine by mouth three times per day (total daily dose = 600mg).
Treatment Week 4: dose will be increased to 250mg of Ezogabine by mouth three times per day (total daily dose = 750mg).
Treatment Week 5: dose will be increased to 300mg of Ezogabine by mouth three times per (total daily dose = 900mg).
Participants will continue to take 900mg of Ezogabine per day and return weekly to the clinic for the remainder of the study.
Following this primary outcome visit, participants will be instructed to taper the study medication over the following 3 weeks based on FDA recommended guidelines as follows:
250 mg po TID daily x 1 week, then 200 mg po daily x 1 week, then 100 mg po daily x 1 week, then discontinue
| Study group | Role | What they receive |
|---|---|---|
| ezogabine | Experimental | Ezogabine dosage plan to 900mg and then tapered down Receives: Drug: ezogabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale Comparison to Baseline
The Montgomery-Asberg Depression Rating Scale (29) is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is rated on a scale of 0 to 6, with differing descriptors for each item. These individual item scores are added together to form a total score, which can range between 0 and 60 points. The MADRS is specifically designed to detect changes in depression severity in the context of a medication treatment trial.
Measured: baseline and after end of treatment (10 weeks)
Secondary outcomes (3)
Patient Rated Inventory of Side Effects (PRISE)
Number of symptom events as reported by the patient in a self-report measure. PRISE assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other)
Measured: 8 weeks
Columbia-Suicide Severity Rating Scale (C-SSRS)
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a comprehensive, semi-structured interview measure that uniquely measures the full spectrum of suicidality including passive and active suicidal ideation, suicidal intent as well as suicidal behaviors. Full range from 0 (low intensity suicidal ideation to 9 (high intensity suicidal ideation).
Measured: 8 weeks
Changes in Reward System Activation After Treatment With Ezogabine
Functional MRI of reward processing: The primary neuroimaging endpoint is the degree of change observed in the reward system in the brain. Although it was an outcome measure, the data format is a set of 4-dimensional statistical maps and not reported in raw data. Mean changes in activation of the ventral tegmental area (VTA) or ventral striatum (VS) in response to reward cue to reward receipt, and VTA mean change in beta weight in response to reward cue at 8 weeks as compared to baseline. The Z-score indicates the number of standard deviations away from a reference population in the same age range. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
Measured: baseline and post treatment (8 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2014 (estimated)
- Study startAug 2014
- Primary completionDec 2016
- Study completionDec 2016
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.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Murrough, Icahn School of Medicine at Mount Sinai
- Investigators
- James Murrough, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02149836
- Sponsor's protocol ID
- GCO 14-0597
- Status last verified
- Mar 2019
- First submitted
- 22 May 2014
- Last updated
- 16 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof-Of-Concept Clinical Trial of a Novel KCNQ Potentiator in Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT02149836
- Acronym / sponsor ID
- GCO 14-0597
- Conditions
- Major Depressive Disorder, Depression
- Keywords
- major depressive disorder, depression, treatment resistent depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 29 May 2014 (estimated)
- Results
- Posted 16 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the antidepressant effects of Ezogabine in major depressive disorder (MDD). The investigators also aim to determine the safety and tolerability Ezogabine in patients with MDD. The investigators hypothesize that depressive symptoms will be significantly decreased following an 8-week treatment period of the medication compared to baseline.
Detailed description
Study Introduction:
Major depressive disorder (MDD) is a global health disease associated with significant morbidity and costs. Many anti-depressants exist within the monoaminergic system yet novel therapeutics are still needed outside of this system. Ezogabine, currently approved by the FDA for adjunctive treatment of partial-onset seizures, may serve as a potential key agent for those with MDD. Ezogabine is known to bind to and activate KCNQ transmembrane K+ ion channels, specifically targeting KCNQ2 in the VTA. Such membrane activity has been show to play a role in previous studies involving a social defeat model of depression. Specifically, data has shown that KCNQ channels were upregulated only in resilient mice and moreover, ezogabine was able to potentiate KCNQ channel activity to result in a fast reversal of the depressed phenotype.
General Investigational Plan:
Objectives:
- Primary Efficacy Objective: To test the antidepressant effects of Ezogabine in MDD.
- Primary Safety Objective: To characterize the safety and tolerability of Ezogabine in patients with MDD.
- Secondary Objectives: To measure the effects of Ezogabine on ventral tegmental area (VTA)-striatal reward circuitry in MDD using reward task-based functional MRI. Rationale: Ezogabine is hypothesized to modulate the firing rate of VTA dopamine (DA) neurons and thereby influence the functioning of the mesolimbic reward system.
Hypotheses
- Efficacy Hypothesis:
Hypothesis 1a: Depressive symptoms will be significantly decreased following an 8-week treatment period compared to baseline, as measured by change in Montgomery-Åsberg Depression Rating Scale (MADRS).
Hypothesis 1b: The antidepressant response rate at study end (defined as 50% in depressive symptoms compared to baseline) will exceed 50%, consistent with known response rates of current antidepressant agents.
- Safety Hypothesis: Ezogabine will be safe and adverse event rates will be similar to rates observed in other adult populations. Specific safety items to be monitored include frequency and intensity of adverse events as measured by the Patient Rated Inventory of Side Effects (PRISE) and treatment-emergent suicidal ideation or behavior as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ezogabine | Experimental | Drug: ezogabineEzogabine dosage plan to 900mg and then tapered down |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female participants, 18-65 years of age;
- Current diagnosis of major depressive disorder according as determined by a psychiatrist and confirmed with The Mini-International Neuropsychiatric Interview (MINI);
- At least moderate depression severity as defined by a score of >= 21 on the Montgomery-Asberg Depression Rating Scale (MADRS);
- At least a moderate level of anhedonia based on a Snaith-Hamilton Pleasure Scale (SHAPS) score ≥ 20;
- If female of childbearing potential, must agree to use of a medically accepted form of contraception, or else agree to abstinent;
Key exclusion criteria (12 listed)
- Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, obsessive compulsive disorder or pervasive developmental disorders or mental retardation;
- Diagnosis of a substance use disorder within the past 6 months (excluding substance use disorder in sustained remission)
- Female participants who are pregnant, nursing, for may become pregnant;
- Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
- Clinically significant abnormalities of laboratories, physical examination, or ECG;
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: Potiga, RetigabineTreatment Week 1: 100mg of Ezogabine by mouth three times per day (total daily dose = 300mg) Treatment Week 2: dose will be increased to 150 mg Ezogabine by mouth three times per day (total daily dose = 450mg). Treatment Week 3: dose will be increased to 200mg of Ezogabine by mouth three times per day (total daily dose = 600mg). Treatment Week 4: dose will be increased to 250mg of Ezogabine by mouth three times per day (total daily dose = 750mg). Treatment Week 5: dose will be increased to 300mg of Ezogabine by mouth three times per (total daily dose = 900mg). Participants will continue to take 900mg of Ezogabine per day and return weekly to the clinic for the remainder of the study. Following this primary outcome visit, participants will be instructed to taper the study medication over the following 3 weeks based on FDA recommended guidelines as follows: 250 mg po TID daily x 1 week, then 200 mg po daily x 1 week, then 100 mg po daily x 1 week, then discontinue | Drug | ezogabine |
Primary outcome
Montgomery-Asberg Depression Rating Scale Comparison to Baseline
Time frame: baseline and after end of treatment (10 weeks)
The Montgomery-Asberg Depression Rating Scale (29) is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is rated on a scale of 0 to 6, with differing descriptors for each item. These individual item scores are added together to form a total score, which can range between 0 and 60 points. The MADRS is specifically designed to detect changes in depression severity in the context of a medication treatment trial.
3 secondary outcomes
Patient Rated Inventory of Side Effects (PRISE)
Time frame: 8 weeks
Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: 8 weeks
Changes in Reward System Activation After Treatment With Ezogabine
Time frame: baseline and post treatment (8 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 principal investigator
Icahn School of Medicine at Mount Sinai
1 site 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 Major Depressive Disorder and Depression, run by Icahn School of Medicine at Mount Sinai at 1 site 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 12 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 16 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 16 Apr 2019). 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?
Montgomery-Asberg Depression Rating Scale Comparison to Baseline (time frame: baseline and after end of treatment (10 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Apr 2019.