An Observational, Retrospective, Single-center, Clinical Study to Evaluate the Efficacy of Sirolimus (Rapamycin) in Patients With Graves' Disease and Moderate-to-severe and Active Graves' Orbitopathy (GO)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- GO overall response
研究概览
简要总结
Graves' Orbitopathy (GO) is a disabling and disfiguring condition associated with Graves' Disease, due to autoimmunity against antigens expressed by the thyroid and orbital tissues, and resulting in orbital fibroblast proliferation and release of glycosaminoglycans. The current treatments available, especially glucocorticoids, are not effective in all patients. Two cases of patients with GO treated with Sirolimus have been reported with an excellent response to the drug.
The rationale for the use of Sirolimus lies in its mechanisms of action. Sirolimus is able to inhibit T-cell activation as well as fibroblast proliferation. In addition, acts indirectly on the Insulin-Like Growth Factor-1 (IGF-1) pathway, and recent clinical trials have shown that a monoclonal antibody against the IGF-1 receptor (Teprotumumab) is effective in patients with GO. Thus, Sirolimus could be used in GO as monotherapy in patients with GO.
The aim of the present drug vs standard treatment, observational study is to evaluate the efficacy of Sirolimus as a second-line treatment in patients with moderately severe, active GO.
详细描述
Study Design: observational
Thirty consecutive patients with moderate-to-severe and active GO treated with sirolimus (15 patients) or methylprednisolone (15 patients) observance 18 consecutive months will be compared.
Study Timeline
Baseline visit - (Time 0) Treatment period (week 1-week 12): daily administration of the trial agent (Sirolimus) or weekly administration of the standard treatment (methylprednisolone) Outcome visit (week 24)
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- •A moderate-to-severe GO, defined as the presence of at least one of the following criteria: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm
- •Active GO: CAS (4) ≥2 out of 7 points in the most affected eye
- •Previous GO treatment with glucocorticoids and/or orbital radiotherapy and/or orbital decompressive surgery, performed more than 24 weeks before the current treatment
- •Male and female patients of age: 18-75 years
排除标准
- •Optic neuropathy
- •Treatment with glucocorticoids or other immunosuppressive medications, and/or selenium, and/or orbital radiotherapy and/or orbital decompressive surgery in the 24 weeks preceding the current treatment
- •Mental illness that prevents patients from comprehensive, written informed consent
研究组 & 干预措施
Sirolimus
Treatment with sirolimus for 12 weeks, given as a second-line treatment
干预措施: Sirolimus (Drug)
Methylprednisolone
Treatment with methylprednisolone for 12 weeks, given as a second-line treatment
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
GO overall response
时间窗: 24 weeks
Percentage of subjects with at least two of the following compared to baseline: a) Improvement in clinical activity score (CAS) by at least 1 point ; b) Improvement in exophthalmos by at least 2 mm; c) Improvement in lid aperture by at least 2 mm; d) Improvement in eye muscle ductions ≥8 degrees; e) Improvement of visual acuity by at least 0.2/1, without worsening of any of these parameters in the contralateral eye if applicable.
次要结局
- Change in exophthalmos(24 weeks)
- Change in the clinical activity score (CAS)(24 weeks)
- Change in quality of life(24 weeks)
- Change in eye ductions(24 weeks)
- Change in eyelid aperture(24 weeks)
- Change in diplopia(24 weeks)
研究者
Marinò Michele
Associate Professor of Endocrinology
University of Pisa