A Proof-Of-Concept Clinical Trial of a Novel KCNQ Potentiator in Major Depressive Disorder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Montgomery-Asberg Depression Rating Scale Comparison to Baseline
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
ezogabine
Ezogabine dosage plan to 900mg and then tapered down
干预措施: ezogabine (Drug)
结局指标
主要结局
Montgomery-Asberg Depression Rating Scale Comparison to Baseline
时间窗: 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.
次要结局
- Columbia-Suicide Severity Rating Scale (C-SSRS)(8 weeks)
- Patient Rated Inventory of Side Effects (PRISE)(8 weeks)
- Changes in Reward System Activation After Treatment With Ezogabine(baseline and post treatment (8 weeks))
研究者
James Murrough
Assistant Professor
Icahn School of Medicine at Mount Sinai