A Proof-of-Concept Trial on the Effect of Ketamine on Fatigue
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Percentage Change in Self-reported Fatigue Visual Analog Scale (VAS) Scale
研究概览
简要总结
Background:
Many people experience fatigue as a side effect of their illnesses and treatments. There are no medicines to treat fatigue, but a drug called ketamine has reduced fatigue in depressed people. Researchers hope that ketamine, compared to a drug called midazolam, can reduce fatigue in people with illnesses.
Objective:
To test whether ketamine reduces fatigue in cancer survivors and people with chronic illness.
Eligibility:
Adults between the ages of 18 and 70 who have fatigue and are cancer survivors or have been diagnosed with a chronic illness such as chronic fatigue syndrome and lupus.
Design:
Participants will be screened with a physical exam, medical history, blood and urine tests, questions about their fatigue, and breathalyzer test.
During phase 1, participants will complete rating their fatigue using questionnaires. They will be provided thinking, memory, and motivation tests. They will also take a handgrip test. For this study, the participant will have an IV, which a needle guides a thin plastic tube (intravenous or IV line) into an arm in their vein. An IV will be required for two of the visits. They will get a single dose of either ketamine or midazolam through an IV line over 40 minutes. Participants must be accompanied by a responsible friend/family/colleague to take them home after getting the study drug.
Participants will have follow-up visits where they repeat the above tests. They will also have follow-up phone calls.
Phase 2 is the same as phase 1, but participants get the other study drug.
The study lasts 1 month. Each phase lasts 2 weeks. Participants will have 6-8 total NIH visits. For the whole study, they will wear a device on their wrists that records physical activity.
Drug side effects can include vivid dreams, seeing colors, perceiving time as moving slower or faster than normal, dizziness, headache, restlessness, nausea, or vomiting, among others.
详细描述
Purpose: The purpose of the study is to investigate the anti-fatigue effects of ketamine in individuals with chronic illness.
Background: Although the underlying mechanisms of fatigue have been studied in several disease conditions, the etiology, mechanisms, and risk factors remain elusive and this symptom remains poorly managed. Fatigue is conceptualized as a multidimensional symptom which incorporates temporal, sensory, cognitive/mental, affective/emotional, behavioral, and physiological dimensions. It is described as a common, chronic, and disabling symptom in individuals with Sjogren s syndrome and those with systemic lupus erythematosus. We recently observed that upregulation of glutamate receptors (e.g.,GRM5) can predict individuals who will develop chronic fatigue one year after completing cancer therapy, suggesting that fatigue may share common glutamatergic markers with depression. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist and has been reported to have rapid anti-depressant effects, and we recently found that it also has rapid anti-fatigue effects. Evidence suggest that severe fatigue in diverse medical conditions is driven by similar biological mechanisms, hence identifying a potential anti-fatigue agent in one medical condition may be a valuable anti-fatigue therapy for other fatiguing conditions.
Population for Study: This proof-of-concept study will enroll 59 individuals (target n of completers = 50) with chronic fatigue.
Key Inclusion/Exclusion Criteria: Participants must have a fatigue visual analog scale (VAS) score of greater than or equal to 50 mm (on a 0-100 mm horizontal scale). The greater than or equal to 50 mm fatigue VAS score is considered clinically important fatigue cutoff score for patients with chronic illness, and also captures the effectivity outcome of a previous pharmacologic intervention for fatigue. The participants must not have any progressive or unstable conditions or be taking medications that cause fatigue.
Methodology: This is a phase II, randomized, double-blind (study team and participants), active comparator-controlled, cross-over trial. After determining eligibility during the screening visit, the participant will be randomized to determine the sequence of study drug/active comparator to take during each phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Ketamine then midazolam administration
Participants receive ketamine 0.5 mg/kg intravenous infusion over 40 minutes followed by a two week washout period then receive midazolam 0.045 mg/kg intravenous infusion over 40 minutes followed by two weeks of observation.
干预措施: Ketamine (Drug)
Ketamine then midazolam administration
Participants receive ketamine 0.5 mg/kg intravenous infusion over 40 minutes followed by a two week washout period then receive midazolam 0.045 mg/kg intravenous infusion over 40 minutes followed by two weeks of observation.
干预措施: Midazolam (Drug)
Midazolam then ketamine administration
Participants receive midazolam 0.045 mg/kg intravenous infusion over 40 minutes followed by a two week washout period then receive ketamine 0.5 mg/kg intravenous infusion over 40 minutes followed by two weeks of observation.
干预措施: Ketamine (Drug)
Midazolam then ketamine administration
Participants receive midazolam 0.045 mg/kg intravenous infusion over 40 minutes followed by a two week washout period then receive ketamine 0.5 mg/kg intravenous infusion over 40 minutes followed by two weeks of observation.
干预措施: Midazolam (Drug)
结局指标
主要结局
Percentage Change in Self-reported Fatigue Visual Analog Scale (VAS) Scale
时间窗: Baseline to three days post infusion for each study arm
Percentage change in self-reported Fatigue Visual Analog Scale (VAS) after a single intravenous dose of the study drug. The Fatigue VAS is a 0-100 mm scale widely used to assess fatigue in patients with chronic illness. Higher score indicates worse fatigue. Change in fatigue VAS scores measured as comparison of fatigue VAS scores collected at the first visit (baseline) and three days post infusion of study drug during each treatment arm (Ketamine, active comparator). Analysis is measured as the difference between day three score minus the baseline score, divided by the baseline score.
次要结局
- Percentage Change in Self-reported Fatigue Visual Analog Scale (VAS) Scale - Day 7(Up to 7 days post infusion for each study drug)
- Areas Under the Curve (AUC) for Percentage Changes in Self-reported Fatigue VAS Score - Through Day 7(Up to 7 days post infusion for each study drug)
- Mean Physical Activity Count Using Actigraphy(Day 7 post infusion)
- Fatigue Level Measured by Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale(Day 7 post infusion)
- Patient Reported Outcome Measurement Information System (PROMIS) - Anxiety Domain(Day 7 post infusion)
- Patient Reported Outcome Measurement Information System (PROMIS) - Depression Domain(Day 7 post infusion)
- Patient Reported Outcome Measurement Information System (PROMIS) - Fatigue Domain(Day 7 post infusion)
- Patient Reported Outcome Measurement Information System (PROMIS) - Sleep Disturbance Domain(Day 7 post infusion)
- Fatigue Level Measured by Fatigue Visual Analogue Scale(Day 7 post infusion)
- Measure of Depression Using the Hamilton Rating Scale for Depression (HAM-D)(Day 7 post infusion)