Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 2
- 主要终点
- Montgomery-Asberg Depression Rating Scale
研究概览
简要总结
The aim of the study is to provide insight into the impact of the immunosuppressant drug sirolimus, on the antidepressant effects of the prototypal rapid-acting antidepressant medication, ketamine.
详细描述
This is a double blind, placebo-controlled, crossover, randomized controlled trial investigating the impact of sirolimus on ketamine's antidepressant effects in participants with antidepressant-resistant depressive symptoms.
Prior to this, there was a phase 1 which included monitoring 3 subjects over the course of 7 days after a single dose of sirolimus and ketamine in order to inquire about side effects or interaction effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Veterans and non-Veterans between the ages of 21-
- •Diagnosis of Major Depressive Episode (unipolar or bipolar) as determined by the Mini International Neuropsychiatric Interview (MINI).
- •Antidepressant-resistant depressive symptoms, defined by a history of failure of one or more adequate antidepressant trials.
- •Stable doses of antidepressants (if prescribed) for a period of four weeks or longer at the time of randomization, except for MAOIs which are prohibited.
- •Stable course of psychotherapy (if engaged in) for a period of four weeks or longer at the time of randomization.
- •Females will be included if they are not pregnant or breastfeeding and agree to utilize a medically accepted birth control method (to include oral, injectable, or implant birth control, condom, diaphragm with spermicide, intrauterine device, tubal ligation, abstinence, or partner with vasectomy) or if post-menopausal for at least 1 year, or surgically sterile. For those women who are taking an oral contraceptive, we will also ask that they use (or ask their partners to use) a barrier method contraceptive.
- •Able to provide written informed consent according to VA HSS guidelines.
- •Ability to read and write in English.
- •A score greater than or equal to 18 on the Montgomery Åsberg Depression Rating Scale (MADRS).
排除标准
- •Subjects with a diagnostic history of schizophrenia or schizoaffective disorder, or currently exhibiting manic or mixed episodes or psychotic features as confirmed by the Mini International Neuropsychiatric Inventory.
- •Current, ongoing serious suicidal risk as assessed by evaluating investigator or by scoring 5 or more on the item-10 of the MADRS.
- •Patients with unstable or inadequately controlled medical conditions.
- •Patient requiring prohibited medication.
- •Patient with history of organ transplant.
- •Meet criteria for a diagnosis of substance dependence (amphetamines, cocaine, hallucinogens, inhalants, opioids, sedatives/hypnotics/anxiolytics) within the three months prior to screening date.
- •Positive urine drug screen for cannabis, cocaine, PCP, or barbiturates.
- •Positive pregnancy test at screening at any screen given during the study.
- •Known sensitivity to sirolimus or ketamine.
- •History of sensitivity to heparin or heparin-induced thrombocytopenia.
- •Resting blood pressure lower than 85/55 or higher than 150/95, or resting heart rate lower than 45/min or higher than 100/min.
研究组 & 干预措施
ketamine + sirolimus (placebo at time 2)
Participants will be treated twice with ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally. After two weeks, they will recieve another infusion of ketamine, and a single dose of placebo.
干预措施: Ketamine (Drug)
ketamine + sirolimus (placebo at time 2)
Participants will be treated twice with ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally. After two weeks, they will recieve another infusion of ketamine, and a single dose of placebo.
干预措施: sirolimus (Drug)
ketamine + sirolimus (placebo at time 2)
Participants will be treated twice with ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally. After two weeks, they will recieve another infusion of ketamine, and a single dose of placebo.
干预措施: Placebo (Drug)
ketamine + placebo (sirolimus at time 2)
Participants will be treated twice with ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg placebo. After two weeks, they will recieve another infusion of ketamine, and a single dose of sirolimus 6 mg.
干预措施: Ketamine (Drug)
ketamine + placebo (sirolimus at time 2)
Participants will be treated twice with ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg placebo. After two weeks, they will recieve another infusion of ketamine, and a single dose of sirolimus 6 mg.
干预措施: sirolimus (Drug)
ketamine + placebo (sirolimus at time 2)
Participants will be treated twice with ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg placebo. After two weeks, they will recieve another infusion of ketamine, and a single dose of sirolimus 6 mg.
干预措施: Placebo (Drug)
结局指标
主要结局
Montgomery-Asberg Depression Rating Scale
时间窗: Pretreatment and 2 week
Montgomery-Asberg Depression Rating Scale (MADRS): The MADRS is a standardized instrument to ascertain depressed mood and neurovegetative signs and symptoms of depression. Ranges from 0-60 (higher is worse).
次要结局
- Quick Inventory of Depressive Symptoms (QIDS)(Pretreatment and 2 week)
- Hamilton Anxiety Rating Scale (HAMA)(Pretreatment and 2 week)
- Clinician Administered Dissociative States Scale (CADSS)(During infusion, approximately 40 mins)
- Positive and Negative Symptom Scale (PANSS) - Positive(During infusion, approximately 40 mins)
- Rapamycin Level(During infusion, approximately 0 mins)
- Ketamine Level(During infusion, approximately 40 mins)