Treatment of SLE with Ajulemic Acid, a Non-Psychoactive Cannabinoid Derivative

用 Ajulemic Acid（一种非精神活性大麻素衍生物）治疗 SLE

基本信息

批准号：
8743075
负责人：
MEGGAN MACKAY
金额：
$ 35.81万
依托单位：
FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-25 至 2016-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8743075
关键词：
9-deoxy-delta-9-prostaglandin D2 Absence of pain sensation Adrenal Cortex Hormones Adverse effects Aftercare American Animal Model Animals Anti Inflammatory Analgesics Anti-Inflammatory Agents Anti-inflammatory Arthritis Atherosclerosis Autoantibodies Biological Markers Blood Cells Bone necrosis Brain Budgets Bursitis CCL2 gene Cannabinoids Case Report Form Cataract Cells Characteristics Chronic Clinical Clinical Trials Consent Forms Constipation Data Collection Development Diabetes Mellitus Diagnosis Disease Documentation Dose Drowsiness Eicosanoids Equipment and supply inventories Future Goals Grant Hemorrhage Human Immune Immune system In Vitro Individual Inflammation Inflammation Mediators Inflammatory Institutional Review Boards Interferons Interleukin-1 Interleukin-6 Investigational Drugs Kidney Label Laboratories Licensing Lupus Manuals Marijuana Measures Mediator of activation protein Mental Depression Metalloproteases Monitor Morbidity - disease rate Musculoskeletal Musculoskeletal Diseases Musculoskeletal Pain Musculoskeletal System Narcotics Nausea Oral Osteoporosis Pain Pamphlets Pathogenesis Patients Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Phase Phase III Clinical Trials Placebos Procedures Process Production Property Proteins Protocols documentation Quality of life Reporting Research Research Personnel Resolution Rheumatoid Arthritis Rheumatology Role Safety Schedule Serum Site Structure Symptoms System Systemic Lupus Erythematosus TNF gene Tendinitis Tetrahydrocannabinol Therapeutic Tissues Toxic effect Trail Making Test United States Food and Drug Administration Visual addiction ajulemic acid analog base belimumab chronic neuropathic pain chronic pain clinical efficacy college cytokine disability gastrointestinal human subject inflammatory pain lipoxin A4 novel novel therapeutics painful neuropathy preclinical study protocol development public health relevance safety testing tool treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Musculoskeletal symptoms, such as arthritis, tendonitis and bursitis, are very common in Systemic Lupus Erythematosus (SLE). Pain and disability from these symptoms can be significant and current treatment options for musculoskeletal pain in SLE include non-steroidal anti-inflammatory medications (NSAIDS), narcotic analgesia and corticosteroids. Each of these is limited by significant potential toxicitie including gastrointestinal bleeding and kidney toxicity in the case of NSAIDS, somnolence, constipation and nausea for narcotics and osteoporosis, osteonecrosis, diabetes, cataracts and atherosclerosis for corticosteroids. Ajulemic acid (AjA) is derived from a class of cannabinoids that retain analgesic and anti-inflammatory properties without the psychotropic effects characteristic of tetrahydrocannabinol (THC; marijuana). AjA has been shown to have potent pain- relieving effects, without psychotropic effects, in animal studies and a clinical trial in human subjects with chronic neuropathic pain. Anti-inflammatory effects of AjA have also been demonstrated in animal models as well as in human subjects and in vitro studies of human inflammatory cells. Thus far, a total of 123 subjects (healthy individuals and patients with neuropathic pain) have received AjA with no serious side effects. The overall purpose of this Phase IIa clinical trial is to evaluate the safety of AjA in SLE patients with mild to moderate musculoskeletal pain and to determine an optimum dose of AjA that will provide maximum benefit and minimal toxicity. Clinical improvement will be determined by assessment of SLE disease activity and changes in pain scales. Studies are also planned to evaluate the mechanisms of action of AjA on circulating inflammatory cells. Based on pre- clinical studies already completed in our laboratory, we expect that AjA will decrease the expression of certain pro-inflammatory proteins in peripheral blood cells and increase the expression of other proteins that enhance the resolution of inflammation.

描述（由申请人提供）：肌肉骨骼症状，如关节炎、肌腱炎和滑囊炎，在系统性红斑狼疮 (SLE) 中非常常见。这些症状引起的疼痛和残疾可能很严重，目前治疗 SLE 肌肉骨骼疼痛的选择包括非甾体抗炎药物 (NSAIDS)、麻醉镇痛和皮质类固醇。其中每一种都受到显着的潜在毒性的限制，包括非甾体抗炎药的胃肠道出血和肾毒性，麻醉药的嗜睡、便秘和恶心，以及皮质类固醇的骨质疏松症、骨坏死、糖尿病、白内障和动脉粥样硬化。 Ajulemic Acid (AjA) 衍生自一类大麻素，它保留了镇痛和抗炎特性，但没有四氢大麻酚 (THC；大麻) 特有的精神作用。动物研究和患有慢性神经性疼痛的人体临床试验表明，AjA 具有有效的止痛作用，但没有精神作用。 AjA 的抗炎作用也已在动物模型、人类受试者和人类炎症细胞的体外研究中得到证实。迄今为止，共有 123 名受试者（健康个体和神经性疼痛患者）接受了 AjA 治疗，没有出现严重的副作用。这项 IIa 期临床试验的总体目的是评估 AjA 在患有轻度至中度肌肉骨骼疼痛的 SLE 患者中的安全性，并确定 AjA 的最佳剂量，以提供最大的益处和最小的毒性。临床改善将通过评估 SLE 疾病活动度和疼痛等级的变化来确定。还计划开展研究评估 AjA 对循环炎症细胞的作用机制。根据我们实验室已经完成的临床前研究，我们预计 AjA 将减少外周血细胞中某些促炎蛋白的表达，并增加其他增强炎症消退的蛋白的表达。