Treatment of Dermatomyositis with Ajulemic Acid, a Non-Psychoactive Cannabinoid

用 Ajulemic Acid（一种非精神活性大麻素）治疗皮肌炎

• 批准号: 8691537
• 负责人: VICTORIA P WERTH
• 金额: $ 17.6万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8691537
• 关键词: Affect; Aftercare; Anti Inflammatory Analgesics; Anti-Inflammatory Agents; Anti-inflammatory; Antimalarials; Area; Autoimmune Process; Biological Markers; Biological Testing; Body Surface Area; Cannabinoids; Cells; Classification; Clinical; Clinical Research; Clinical Trials; Connective Tissue Diseases; Controlled Clinical Trials; Cutaneous; Data; Data Collection; Databases; Dermatology; Dermatomyositis; Development; Disease; Disease Attributes; Dose; Equipment and supply inventories; Evaluation; Future; Glucocorticoids; Goals; Health; Immune; Immunosuppressive Agents; Individual; Inflammation Mediators; Inflammatory; Interferon Type I; Interferons; Interleukin-1; International; Intravenous Immunoglobulins; Lesion; Link; Marijuana; Measures; Mediator of activation protein; Medical; Mental Depression; Muscle; Myopathy; Myositis; Outcome; Outcome Study; Pathogenesis; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Phase I Clinical Trials; Phase II Clinical Trials; Pilot Projects; Placebo Control; Placebos; Population; Process; Production; Property; Prospective Studies; Pruritus; Quality of life; Randomized; Reaction; Refractory; Refractory Disease; Research; Role; Safety; Sampling; Serum; Severities; Severity of illness; Skin; Skin Manifestations; Societies; Systemic Therapy; Systemic disease; TNF gene; Therapeutic; Tissues; Toxic effect; Translational Research; Tumor Necrosis Factor-alpha; Validation; Work; addiction; ajulemic acid; clinical efficacy; cohort; cytokine; design; indexing; novel; novel strategies; prospective; research study; safety testing; skin disorder; skin lesion; standardize measure; tool

DESCRIPTION (provided by applicant): Dermatomyositis (DM) is a severe autoimmune connective tissue disease in which patients routinely endure prolonged courses of systemic treatments that are associated with significant toxicity for their skin disease. Although over 60,000 individuals have DM in the U.S., the majority of whom have skin findings, there have been no prospective studies of treatments for the many patients with skin predominant disease. The goal of this proposal is to initiate a short-term (12 week treatment) clinical study to examine the role of ajulemic acid for patients with refractory dermatomyositis (DM) involving the skin. Patients with skin manifestations of dermatomyositis have extremely poor quality of life, including severe pruritus and depression, and current therapies are frequently ineffective. First line treatment for the skin is antimalarials, which frequently are not effective or cause drug reactions. We propose a randomized placebo-controlled clinical trial in DM patients with refractory skin disease, to test the safety and explore the clinical efficacy of ajulemic acid (AjA, a synthetic, nonpsychoactive, anti-inflammatory, analgesic cannabinoid, compared to placebo for the treatment of skin disease associated with DM. We anticipate that results from the proposed clinical trial will be used to power a larger Phase II clinical trial for clinical efficac of AjA. To test biological efficacy of AjA, serum levels and PBMC production of IL-1β, IFNγ, IFNα, TNFα, and expression in PBMC of the IFNα signature will be examined before and after dosing. Successful completion of these studies should also allow us to determine biomarker endpoints for clinical efficacy to be used in a larger clinical trial. There is a great need for new approachs to treatment of the skin lesions of patients with dermatomyositis. This clinical study will allow careful observation of a potentially exciting new treatment.

描述（由申请人提供）：皮肌炎（DM）是一种严重的自身免疫性结缔组织疾病，患者通常要忍受长时间的全身治疗，这与其皮肤病的显着毒性相关。尽管在美国有超过 60,000 人患有 DM，其中大多数有皮肤问题，但尚未对许多以皮肤为主的疾病患者进行治疗的前瞻性研究。该提案的目标是启动一项短期（12 周治疗）临床研究，以检查 ajulemic 酸对涉及皮肤的难治性皮肌炎 (DM) 患者的作用。具有皮肌炎皮肤表现的患者生活质量极差，包括严重瘙痒和抑郁，目前的治疗方法常常无效。皮肤的一线治疗是抗疟药，但通常无效或引起药物反应。我们提议在患有难治性皮肤病的 DM 患者中进行一项随机安慰剂对照临床试验，以测试 ajulemic Acid（AjA，一种合成的、非精神活性的、抗炎、镇痛的大麻素）的安全性并探索其临床疗效，与安慰剂相比，用于治疗与 DM 相关的皮肤病。我们预计拟议的临床试验的结果将用于为更大规模的 II 期临床试验提供动力 AjA 的临床疗效。为了测试 AjA 的生物学功效，将在给药前和给药后检查血清水平和 PBMC 中 IL-1β、IFNγ、IFNα、TNFα 的产生，以及 PBMC 中 IFNα 特征的表达。这些研究的成功完成还应该使我们能够确定临床疗效的生物标志物终点，以用于更大规模的临床试验。非常需要新的 皮肌炎患者皮损的治疗方法。这项临床研究将允许仔细观察潜在的令人兴奋的新疗法。