Double Blind Placebo Controlled Study of Outpatient Intravenous Ketamine for the Treatment of CRPS
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- The purpose of this study is to evaluate intravenous outpatient infusion of sub-anesthetic doses of ketamine for the treatment of CRPS by a 30% pain reduction post treatment
研究概览
简要总结
Complex Regional Pain Syndrome is a debilitating and extremely difficult to treat condition. There is a large body of evidence demonstrating the therapeutic value of N-methyl-D-aspartate (NMDA)-receptor antagonists in CRPS. The NMDA antagonist ketamine has been shown to be effective in the treatment of CRPS, resulting in complete remission of the disease in some patients. The purpose of this study is to evaluate intravenous outpatient infusion of sub-anesthetic doses of ketamine for the treatment of CRPS. A thorough evaluation of this procedure, providing information into the degree of relief and which of the constellation of RSD symptoms are best alleviated by this procedure would result in the optimization of this therapy for the treatment of CRPS.
详细描述
PRE TREATMENT:
Prior to treatment, after informed consent is obtained, each subject will be randomized into the ketamine or placebo (normal saline) infusion group. Both the patient and all other individuals involved in the study will be blinded as to the treatment except Guillermo Alexander PhD who will be responsible for the randomization and Margaret Rose RN who will be responsible for preparing the infusion solution. The patient will then receive a complete neurological examination and will be asked to complete a short form McGill and Quality of life questionnaires (Attachment 1).
Two weeks before treatment, 2 week and 3 months post treatment the following sensory and motor tests will be performed.
Thermal Detection Thresholds: Cool detection thresholds, which are mediated via A fibers and warm detection thresholds, which are mediated by small unmyelinated C fibers, will be determined using the TSA-II NeuroSensory Analyzer (Medoc Advanced Medical Systems U.S., Minneapolis, MN). The device consists of a computer controlled thermoelectric probe with a surface area of 9 cm2 that is attached using a velcro strap to the area of skin to be tested (thenar eminence and hypothenar eminence in the hands and the dorsal foot). For each trial the thermal stimulator starts at the thermo-neutral baseline temperature of 32oC, and increases for warming thresholds, or decreases for cooling thresholds, linearly at a rate of 1oC per second, until the subject pushes a button that stops and records the temperature and returns the unit to baseline temperature. Three trials are averaged for cool and for warm threshold for each site tested.
Thermal Pain: Thermal pain tolerance will be determined at the same sites and using the same method described above for thermal detection thresholds. The only difference is that for thermal pain trials, the subject will be instructed to push the control button (which immediately resets the stimulator back to baseline temperature) when the thermal stimulus (cold or hot) becomes painful. The TSA-II hardware automatically resets if the temperature reaches -10oC (for cooling) or 50oC (for heating) and the control button has not been pushed. This temperature range has been determined to not cause damage to skin or underlying tissue.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Patients diagnosed with CRPS based on the modified IASP (International Association for the Study of Pain) research criteria (Harden RN and Bruehl SP
- •Diagnostic Criteria: The Statistical Derivation of the Four Criterion Factors.
- •In CRPS: Current Diagnosis and Therapy, Progress in Pain Research and Management, Vol 32: pp 45-58, 2005), whose condition is intractable for at least six months and have failed at least three of the following therapies:
- •Nerve blocks
- •Opioid analgesics
- •Non-opioid analgesics
- •Non-steroidal anti-inflammatory drugs
- •Anti-seizure medications
- •Antidepressants
- •Muscle relaxants; or
- •Physical therapy.
- •The patients must be ketamine naïve and can be of either gender including all racial and minority groups. The patient's age must be between 18 and 65 years, inclusive.
- •The study subjects must report pain levels equal to or greater than 4 on a scale of 0-10 (0 = no pain and 10 = unbearable pain). The pain must be stable over time and not vary more that 1 pain level.
- •The patient must be on a stable dose of CRPS medications for 28 days prior to and throughout the duration of the study.
- •The patient must be accompanied by a responsible adult.
- •The patient will be instructed that he/she will not be allowed to drive home following the infusion. Therefore in order to be included in the study the subjects must arrange for transportation for the 10 day duration of the study.
排除标准
- •Patients less than 18 years of age will be excluded. In this initial study, patients over 65 years of age will be excluded due to possible unforeseen concomitant medical problem.
- •Patients that have previously undergone intravenous ketamine infusions will be excluded from the study.
- •Patients who are pregnant, are lactating, have known psychotic or psychiatric illness, are afflicted with glaucoma or have thyrotoxicosis will also be excluded.
- •Any patient that is unable to provide consent due to cognitive difficulties will not be used in this study.
- •Patients that can not provide the means to be transported home following daily infusions will be excluded from the study.
- •The investigators feel that issues concerning monetary gain and or loss due to the patient's medical condition may adversely affect the study, therefore, patients with active litigation, compensation or disability issues related to their CRPS will be excluded.
- •Patients with a history of substance abuse will be excluded.
- •Patients on certain blood pressure lowering medications such as calcium blockers, or beta blockers will be excluded from the study.
- •Patients with major medical problems including but not limited to; uncontrolled hypertension, hypotension, cardiac failure, renal failure or liver failure will not be used in this study.
研究组 & 干预措施
1
干预措施: IV NSS (Other)
1
干预措施: Normal Saline (Other)
2
INFUSION PLAN:
All patients will be infused intravenously with 100 ml of normal saline with or without ketamine for four hours (25 ml/hr) daily for 10 days. The maximum intravenous ketamine infusion dose for this study will be 0.35 mg/kg/hr, not to exceed 25 mg/hr (100 mg of ketamine over a 4 hour period). On the first day, the intravenous ketamine infusion will be set to 50% of the maximum rate. On the second day, the intravenous ketamine infusion will be increased to 75% of the maximum rate. On the third day, the intravenous ketamine infusion will be increased to the maximum rate. The daily ketamine infusion rate is maintained at this level for the duration of the ten day study.
干预措施: Ketamine (Drug)
结局指标
主要结局
The purpose of this study is to evaluate intravenous outpatient infusion of sub-anesthetic doses of ketamine for the treatment of CRPS by a 30% pain reduction post treatment
时间窗: Patients will be evaluated for three months after treatment
次要结局
- Lenght of relief of pain(When and if pain returns to pre treatment levels)