Experimental Therapeutics for Chronic Pain and Symptoms Management

慢性疼痛和症状管理的实验疗法

基本信息

批准号：
8554726
负责人：
Leorey Saligan
金额：
$ 45.01万
依托单位：
NATIONAL INSTITUTE OF NURSING RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8554726
关键词：
Activities of Daily Living Affect Age American Antidepressive Agents Anxiety Anxiety Disorders Area Articular Range of Motion Back Bilateral Blood flow Caring Causalgia Chronic Clinical Clinical Trials Collection Complex Regional Pain Syndromes Cross-Over Studies Cutaneous Data Diagnosis Diagnostic Disease Double-Blind Method Drops Edema Enrollment Esthesia Evaluation Exclusion Criteria Fatigue Female Fibromyalgia Health Hyperalgesia Impairment Individual Institutional Review Boards International Intervention Japan Joints Limb structure Location Manuals Measurement Measures Mental Depression Mood Disorders Names Oryctolagus cuniculus Outcome Measure Outpatients Pain Pain intensity Patient Outcomes Assessments Patients Peripheral Nerves Pharmaceutical Preparations Phase Physical Examination Physical Function Placebo Control Placebos Protocols documentation Quality of life Questionnaires Randomized Recording of previous events Reflex Sympathetic Dystrophy Regimen Reporting Research Rheumatology SF-36 Safety Self-Administered Site Skin Sleep Sleep disturbances Specific qualifier value Swelling Symptoms Syndrome Tablets Temperature Testing Therapeutic Tissue Extracts Tissues United States United States National Institutes of Health Vaccinia virus Walking Woman Work allodynia base chronic neuropathic pain chronic pain clinical efficacy college design dosage drug testing inclusion criteria male meetings nerve injury neurotropin novel pressure primary outcome skin color spontaneous pain symptom management tertiary care trapezius muscle

项目摘要

Patients with Complex Regional Pain Syndrome, type I (CRPS-I), formerly termed Reflex Sympathetic Dystrophy, have chronic, post-traumatic pain that spreads beyond the distribution of any single peripheral nerve without evidence of major peripheral nerve damage. A similar disorder, Causalgia, re-named CRPS-II, presents with clear evidence of nerve injury. No successful drug treatment exists for these disorders. Neurotropin is a non-protein extract of cutaneous tissue from rabbits inoculated with vaccinia virus. Neurotropin tablets, prepared from the tissue extract, have been used extensively in Japan to treat CRPS and other painful conditions; however, the drug has not undergone clinical therapeutic testing in the United States. Protocol (00-NR-0200) was designed to carry out double-blind, placebo-controlled, crossover studies about clinical efficacy of Neurotropin (FDA IND # 60,994) for chronic neuropathic pain in outpatients with CRPS-I or II. Subjects of this double blind cross-over study receive Neurotropin or placebo tablets for 5 weeks, then no trial medication for at least 1 week, and then the other trial drug for the next 5 weeks. That is, patients who took placebo the first 5 weeks will take Neurotropin the second 5 weeks and vice versa. Thirty male and female patients (age range: 18 and older) meeting the diagnostic criteria established by the International Association for the Study of Pain for diagnosis of CRPS who have been treated unsuccessfully with a current standard therapeutic regimen will be selected for the study. The CRPS patients are given the test drug (4 tablets, twice daily) orally for 5 weeks. After the washout period (at least 1 week), the other test drug was administered to the same patient. Before first treatment phase and after 5 weeks of each treatment phase, the pain sensation (area, spontaneous pain intensity, allodynia, hyperalgesia), quality of life (SF-36 questionnaire), autonomic function (skin color, skin blood flow and temperature), edema/swelling of affected limb, and active range of motion of involved joints are measured. The protocol has completed enrolment of 16 patients. An interim analyses was conducted and the research team decided to terminate the study based on the findings of the interim analysis. IRB approval was obtained for the termination of the protocol. A parallel protocol is evaluating the use of neurotropin for fibromyalgia (FM), a disabling disorder that primarily affects women and presents a therapeutic challenge. Because of the reported efficacy of Neurotropin for treatment of FM in Japan, we have planned a double-blind, placebo-controlled, crossover studies to confirm these reports. The study is designed to test whether Neurotropin treatment will affect spontaneous pain, sensitivity to pressure-induced pain at specific locations, and/or the ability of the patient to function in normal activities as well as affect the fatigue, sleep disturbance, anxiety and mood disorder frequently seen in fibromyalgia patients. Female patients (age range: 18 and older) meeting the criteria established by the American College of Rheumatology for diagnosis of FM who have been treated unsuccessfully with a current standard therapeutic regimen are selected for the study. The criteria are (A) a history of widespread pain (in all quadrants and back) for more than half of the days in each of the prior three months and (B) the required number (11) of tender points of 18 test sites, which will be determined during the initial physical examination. The average score on the Fibromyalgia Impact Questionnaire (FIQ: a brief 10-item self-administered measure of physical functioning, ability to work and perform activities of daily living, depression, anxiety, sleep, pain, stiffness and fatigue) for patients seen in tertiary care settings is about 50 (with 100 being the maximum, a higher score indicating a greater impairment of health) and we will include only those patients in whom the FIQ score is greater than 30 at the initial evaluation. To be admitted to this study, patients must be willing to continue using only their present medications (including antidepressants) or other forms of care related to the control of FM symptoms during the course of the study. Because Neurotropin may take several weeks to have an effect and because FM has such a spontaneously fluctuating course, in this study test tablets will be administered over a 12-week interval. Neurotropin or matching placebo will be randomly assigned as the first treatment. During the first 12-week treatment patients will be given Neurotropin or placebo tablets. After more than 1 week wash-out period, the patient will receive a second 12-week supply of placebo (for those patients who received Neurotropin tablets) or Neurotropin tablets (for those patients who received placebo tablets). In both treatment phases, the patient is instructed to take 8 tablets daily (4 tablets twice daily), the dosage used in Japan and in another NIH protocol (00-NR-0200) for clinical trial of Neurotropin in patients with CRPS. Before each treatment phase and every 6 week during each treatment phase, the FIQ, SF-36, the manual tender point count, the dolorimetric estimate of overall tenderness and the six minute walk test are measured. Differences in the FIQ scores during and at the end of the study period will be used as the primary outcome measure. The 18 (9 bilateral) specified locations are examined for tender points. The dolorimetric measurement of mean pressure thresholds to elicit pain determined at three paired points (epicondyle, mid-trapezius, and thumbnail) assesses overall tenderness. Currently, the protocol has screened a total of 56 patients, 28 patients have completed the study, 12 dropped out, and 3 are actively enrolled.

具有复杂区域疼痛综合征的患者，I型（CRPS-I）以前称为反射性交感神经营养不良，具有慢性，创伤后疼痛，它们的传播超出了任何单个外周神经的分布，而没有严重的外周神经损伤的证据。一种类似的疾病，因果关系，重新命名为CRPS-II，呈现出明确的神经损伤的证据。这些疾病不存在成功的药物治疗。神经性蛋白是从接种牛vicinia病毒的兔子的皮肤组织的非蛋白质提取物。由组织提取物制备的神经性片剂已在日本广泛使用，以治疗CRP和其他疼痛状况。但是，在美国，该药物尚未进行临床治疗测试。方案（00-NR-0200）的设计旨在进行有关神经运动的临床疗效（FDA IND＃60,994）对CRPS-I或II的慢性神经性疼痛的临床疗效（FDA IND＃60,994）的临床疗效。这项双盲跨界研究的受试者接受神经支出或安慰剂片5周，然后在至少1周内没有试用药物，然后在接下来的5周内进行其他试验药物。也就是说，前5周的安慰剂患者将在第二个5周内服用神经支出，反之亦然。 30名男性和女性患者（年龄范围：18岁以上）符合国际诊断协会的诊断标准，该协会的CRP诊断诊断为诊断，而CRP的诊断为诊断，这些CRP的诊断将通过当前的标准治疗方案未成功治疗。给予CRPS患者的测试药物（每天两次，两次）口服5周。洗涤期（至少1周）后，将另一种测试药物给予同一患者。在第一个治疗阶段和每个治疗阶段5周之前，疼痛感觉（面积，自发性疼痛强度，异常性症，痛觉过敏），生活质量（SF-36问卷），自主神经功能（皮肤颜色，皮肤血液流量和温度），受影响的LIMB的水肿/肿胀以及涉及关节运动的活动范围。该方案已完成16名患者的入学人数。进行了临时分析，研究小组决定根据临时分析的发现终止研究。获得了IRB批准以终止协议。平行方案是评估神经运动对纤维肌痛（FM）的使用，纤维肌痛（FM）是一种主要影响女性并提出治疗挑战的残疾疾病。由于据报道，神经运动在日本治疗FM的功效，我们计划进行双盲，安慰剂对照的跨界研究来确认这些报告。该研究旨在测试神经支出治疗是否会影响自发性疼痛，对特定位置的压力诱发的疼痛的敏感性以及/或患者在正常活动中起作用，并影响纤维肌痛患者经常看到的疲劳，睡眠障碍，焦虑和情绪障碍。女性患者（年龄范围：18岁及以上）符合美国风湿病学院针对FM诊断的标准，这些标准已选择了当前的标准治疗方案未成功治疗的FM。标准是（a）在前三个月中的每个象限中（在所有象限和背部）中的广泛疼痛病史，以及（b）18个测试地点的招标点（11）的招标数（11），这将在初次体格检查期间确定。纤维肌痛影响问卷的平均得分（FIQ：短暂的10个项目的自我管理量度，衡量身体功能，工作能力和进行日常生活，抑郁，焦虑，睡眠，睡眠，疼痛，疼痛，僵硬和疲劳的能力，在第三级护理中所见的患者比50分（其中100个）比最高的患者更高，而在健康中更高，我们将在健康方面更高，我们将在健康方面更高，我们将获得更高的成绩。评估。要接受这项研究，患者必须愿意继续仅使用其目前的药物（包括抗抑郁药）或与FM症状有关的其他形式的护理。由于神经支出可能需要几周才能产生效果，并且由于FM具有如此自发的波动课程，因此在这项研究中，将在12周的间隔内进行测试片。神经支出或匹配的安慰剂将被随机分配为第一种治疗方法。在第一个12周的治疗期间，将为患者提供神经运动或安慰剂片。经过1周以上的清洗期，该患者将获得第二次为期12周的安慰剂（对于那些接受神经性片剂的患者）或神经性片剂（对于那些接受安慰剂片的患者）。在这两个治疗阶段中，指示患者每天服用8片（每天两次），日本使用的剂量和另一种NIH方案（00-NR-0200）（00-NR-0200）用于CRPS患者的临床试验。在每个治疗阶段和每个治疗阶段的每6周之前，都测量了FIQ，SF-36，手动招标点计数，整体压痛的多毛估计和六分钟步行测试。研究期间和结束时FIQ得分的差异将用作主要结果指标。检查了18个（9个双边）指定位置的招标点。对平均压力阈值的二左测量值在三个配对点（Epicondyle，Mid-Strapezius和Thumbnail）下确定的疼痛评估了整体压痛。目前，该方案总共筛选了56例患者，28例患者完成了研究，12例辍学，3例被积极招募。