Nitrous Oxide as Treatment for Fibromyalgia
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Monitor changes in NPRS score
研究概览
简要总结
The purpose of this study is to explore a potential role of nitrous oxide in treating pain associated with fibromyalgia.
详细描述
Investigators are conducting this trial to determine the efficacy of nitrous oxide on fibromyalgia, a chronic, debilitating, disorder typified by widespread musculoskeletal pain, accompanied by symptoms of fatigue, affected sleep, memory issues, and mood disorders.
Studies suggests that the chronic widespread pain seen in fibromyalgia patients has a neurogenic origin. Higher levels of ascending pathway neurochemicals, including nerve growth factor, substance P, and brain derived neurotrophic factor, are present in the cerebrospinal fluid (CSF) of fibromyalgia patients when compared to healthy controls. In addition, glutamate levels can be elevated in both the CSF and brain of fibromyalgia patients. Glutamate may play a central role, by acting on the NMDA-receptors to increase the central amplification of pain perception, which is thought to manifest as allodynia and hyperalgesia in fibromyalgia patients. NMDA-receptors are thus an attractive target for fibromyalgia therapeutic drug development.
In four other randomized controlled trial(s) to evaluate ketamine an NMDA-receptor antagonist; two demonstrated an acute reduction in VAS pain scores (20- to -25 points) 90- to 120-minutes following IV ketamine 0.3 mg/kg compared with placebo; while the other two using different drug concentrations and dose regimen (0.3 mg/kg over 30 minutes and 0.5 mg/kg for 3 hours) showed a 0.5- to 0.9-point reduction in pain scores (10-cm VAS) at 90 to 180 minutes following IV ketamine compared with placebo. Although all four trials demonstrated significant acute pain improvement during and immediately following the infusions, there were no sustained improvements.
Given nitrous oxide is another drug with known NMDA-receptor antagonism, this trial will evaluate the efficacy of inhaled 50% nitrous oxide compared to placebo (oxygen-air mixture). Study participants with a clinical diagnosis of fibromyalgia, meeting 2016-Fibromyalgia Diagnostic Criteria (2016-ACR) and neuropathic pain criterion will be randomly assigned to receive two, 60-minute inhalation sessions (50% nitrous oxide and placebo).
Treatment outcomes will be monitored using diagnostic tools measuring functionality, pain, and mood:
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, Outcomes Assessor)
盲法说明
Patient and assessor blinded to study group assigned
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •2016 American College of Rheumatology Revised criteria for fibromyalgia (2016-ACR)
- •Subjects 18 -75 years of age.
- •Self-reported pain of at least 4 on the Numeric Pain Rating Scale (NPRS) at screening and baseline.
- •Subject receives and agrees to remain on their stable fibromyalgia treatment plan established at least 4 weeks prior to dosing. Stable means no change in dose or any pain medication.
- •Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments
- •If currently on psychotherapy, it must have been maintained at the same frequency for 4 weeks prior to treatment.
排除标准
- •Unstable doses of allowed antidepressants or muscle relaxants or dosages for any other medical condition.
- •Pain due to concurrent autoimmune or inflammatory disease such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, or other chronic widespread pain condition(s) that may confound fibromyalgia pain.
- •Psychiatric or cognitive disorder (e.g., current schizophrenia, severe depression, suicidal ideation, dementia, etc.) that the investigator or sponsor considers significant for this study.
- •Clinically significant alcohol or other substance abuse within the last 2 years, in the opinion of the investigator.
- •Current or recent history of medically inappropriate or illegal use of drugs of abuse including benzodiazepines, opiates, cocaine, cannabinoids, and amphetamines.
- •Current treatment with N-methyl-D-aspartate receptor (NMDAR) ligands including ketamine, amantadine, dextromethorphan, memantine, methadone, or dextropropoxyphene.
- •Subjects who are pregnant, breast feeding, or planning to become pregnant during the course of the study and for 28 days after the final administration of investigational product.
- •Any other serious medical condition affecting heart, lung or any other organ system.
- •Any impairment, activity or situation that in the judgment of the investigator would prevent satisfactory completion of the study protocol.
研究组 & 干预措施
Treatment; Nitrous Oxide 50%
A single 60-minute session of inhaled 50% nitrous oxide.
干预措施: Nitrous oxide gas for inhalation (Drug)
Control; Oxygen-air mixture
A single 60-minute session of inhaled Oxygen-air mixture
干预措施: Placebo (Drug)
结局指标
主要结局
Monitor changes in NPRS score
时间窗: Over 8-weeks from baseline (length of study participation)
Monitoring changes in 'Numeric Pain Rating Scale' (NPRS) diagnostic score to determine effectiveness a 60-minute session of inhaled 50% nitrous oxide vs placebo has on symptoms associated with fibromyalgia. The NPRS is a validated self-report diagnostic asking patients to indicate the intensity of current, best, and worst pain levels over the past 24 hours on a scale of 0 (no pain) to 10 (worst pain imaginable). Response and remission will be based on a 30% improvement in average daily mean (max and min) NPRS score.
次要结局
- Changes in FIQR(Over 8-weeks from baseline (length of study participation))
- Changes in Global Impression of Change Scale(Over 8-weeks from baseline (length of study participation))
- Computerize Adaptive Testing - Mental Health (CAT-MH) measurements(Over 8-weeks from baseline)
- Hospital Anxiety and Depression Scale(Over 8-weeks from baseline (length of study participation))
- Changes in FIQR(Over 8-weeks from baseline (length of study participation))
- Changes in Global Impression of Change Scale(Over 8-weeks from baseline (length of study participation))
- Computerize Adaptive Testing - Mental Health (CAT-MH) measurements(Over 8-weeks from baseline)
- Hospital Anxiety and Depression Scale(Over 8-weeks from baseline (length of study participation))