Back to resultsStudy to Treat Major Depressive Disorder (MDD) With a New Medication
Primary Purpose
Major Depressive Disorder, Depression
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ezogabine
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder focused on measuring major depressive disorder, depression, treatment resistent depression
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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;
- 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.
Sites / Locations
- Icahn School of Medicine at Mount Sinai
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ezogabine
Arm Description
Ezogabine dosage plan to 900mg and then tapered down
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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)
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).
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.
Full Information
NCT ID
NCT02149836
First Posted
May 22, 2014
Last Updated
March 26, 2019
Sponsor
Icahn School of Medicine at Mount Sinai
1. Study Identification
Unique Protocol Identification Number
NCT02149836
Brief Title
Study to Treat Major Depressive Disorder (MDD) With a New Medication
Official Title
A Proof-Of-Concept Clinical Trial of a Novel KCNQ Potentiator in Major Depressive Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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. 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:
A. Primary Efficacy Objective: To test the antidepressant effects of Ezogabine in MDD.
B. Primary Safety Objective: To characterize the safety and tolerability of Ezogabine in patients with MDD.
C. 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
A. 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.
B. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Depression
Keywords
major depressive disorder, depression, treatment resistent depression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ezogabine
Arm Type
Experimental
Arm Description
Ezogabine dosage plan to 900mg and then tapered down
Intervention Type
Drug
Intervention Name(s)
ezogabine
Other Intervention Name(s)
Potiga, Retigabine
Intervention Description
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
Primary Outcome Measure Information:
Title
Montgomery-Asberg Depression Rating Scale Comparison to Baseline
Description
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.
Time Frame
baseline and after end of treatment (10 weeks)
Secondary Outcome Measure Information:
Title
Patient Rated Inventory of Side Effects (PRISE)
Description
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)
Time Frame
8 weeks
Title
Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
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).
Time Frame
8 weeks
Title
Changes in Reward System Activation After Treatment With Ezogabine
Description
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.
Time Frame
baseline and post treatment (8 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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;
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Murrough, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
12. IPD Sharing Statement
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Study to Treat Major Depressive Disorder (MDD) With a New Medication
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