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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.

患有I型复杂性局部疼痛综合征（CRPS-I）（以前称为反射性交感神经营养不良）的患者患有慢性创伤后疼痛，其扩散超出任何单一外周神经的分布，而没有主要外周神经损伤的证据。一种类似的疾病，Causgia，重新命名为CRPS-II，有明显的神经损伤证据。对于这些疾病没有成功的药物治疗。神经妥乐平是从接种牛痘病毒的兔子皮肤组织中提取的非蛋白质提取物。从组织提取物制备的神经妥乐平片剂在日本已被广泛用于治疗CRPS和其他疼痛状况;然而，该药物尚未在美国进行临床治疗测试。方案（00-NR-0200）旨在进行关于神经妥乐平（FDA IND #60，994）治疗CRPS-I或II门诊患者慢性神经性疼痛的临床疗效的双盲、安慰剂对照、交叉研究。该双盲交叉研究的受试者接受神经妥乐平或安慰剂片剂5周，然后至少1周不接受试验药物，然后在接下来的5周接受另一种试验药物。也就是说，前5周服用安慰剂的患者将在后5周服用神经妥乐平，反之亦然。本研究将选择30例符合国际疼痛研究协会制定的CRPS诊断标准且当前标准治疗方案治疗失败的男性和女性患者（年龄范围：18岁及以上）。给CRPS患者口服试验药物（4片，每日两次），持续5周。洗脱期（至少1周）后，对同一患者给予另一种试验药物。在第一治疗阶段之前和每个治疗阶段的5周之后，测量疼痛感觉（面积、自发性疼痛强度、异常性疼痛、痛觉过敏）、生活质量（SF-36问卷）、自主神经功能（皮肤颜色、皮肤血流和温度）、患肢的水肿/肿胀和受累关节的活动范围。该方案已完成16例患者的入组。进行了中期分析，研究团队决定根据中期分析的结果终止研究。获得IRB批准终止方案。一个平行的协议是评估使用神经妥乐平纤维肌痛（FM），致残性疾病，主要影响妇女和提出了一个治疗挑战。由于在日本报道了神经妥乐平治疗FM的疗效，我们计划进行一项双盲、安慰剂对照、交叉研究来证实这些报道。该研究旨在测试神经妥乐平治疗是否会影响自发性疼痛、对特定部位压力诱发疼痛的敏感性和/或患者在正常活动中发挥功能的能力，以及影响纤维肌痛患者中常见的疲劳、睡眠障碍、焦虑和情绪障碍。女性患者（年龄范围：18岁及以上）的患者被选择用于本研究，这些患者符合美国流变学学会建立的诊断FM的标准，并且用目前的标准治疗方案治疗失败。标准是：（A）在前三个月的每个月中，有超过一半的天数有广泛疼痛史（所有象限和背部）;（B）18个测试部位的压痛点的要求数量（11个），这将在初次体检期间确定。纤维肌痛影响问卷的平均得分（FIQ：一个简短的10项自我管理措施的身体功能，工作能力和日常生活活动的执行，抑郁，焦虑，睡眠，疼痛，僵硬和疲劳）的病人看到在三级保健设置是约50（100为最大值，分数越高表明健康受损越严重），我们将仅纳入初始评估时FIQ分数大于30的患者。要进入本研究，患者必须愿意在研究过程中继续仅使用其目前的药物（包括抗抑郁药）或与FM症状控制相关的其他形式的护理。由于神经妥乐平可能需要几周才能产生效果，并且因为FM具有这样的自发波动过程，因此在本研究中，将在12周的间隔内施用测试片剂。神经妥乐平或匹配的安慰剂将被随机分配为首次治疗。在前12周的治疗期间，患者将被给予神经妥乐平或安慰剂片剂。超过1周的洗脱期后，患者将接受第二次12周的安慰剂（对于接受神经妥乐平片剂的患者）或神经妥乐平片剂（对于接受安慰剂片剂的患者）。在两个治疗阶段，指导患者每天服用8片（4片，每天两次），这是在日本和另一个NIH方案（00-NR-0200）中使用的剂量，用于CRPS患者的神经妥乐平临床试验。在每个治疗阶段之前和在每个治疗阶段期间每6周，测量FIQ、SF-36、手动压痛点计数、总压痛的疼痛估计和6分钟步行试验。研究期间和研究结束时FIQ评分的差异将用作主要结局指标。对18个（9个双边）指定地点进行招标点审查。在三个配对点（上髁、中髁和拇指甲）测定平均压力阈值以引起疼痛的痛度测量评估总体压痛。目前，该方案共筛选了56例患者，28例患者已完成研究，12例退出，3例正在积极入组。