Adjunctive Atorvastatin in Moderate-to-severe Thyroid Eye Disease (SEMAR-TED: Structural, Biomarker Expression and Muscle Endpoints of Atorvastatin): Study Protocol for a Randomised, Open-label, Assessor-masked Controlled Trial
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Individual rectus muscle diameters
研究概览
简要总结
The trial tests the hypothesis that, in adults with active, moderate-to-severe Graves' orbitopathy, 24 weeks of oral atorvastatin 20 mg daily added to a standard 12-week course of intravenous methylprednisolone produces a greater reduction in extraocular muscle size than intravenous methylprednisolone alone, and that any such reduction is accompanied by lower expression of TSH receptor, IGF-1 receptor, PDGF receptor, PI3K/AKT and miR-155 transcripts, and higher expression of miR-146a. The prespecified direction for miR-146a follows its reported suppression in CD4+ T cells in active disease [26]. Reported directions of change are compartment-specific and not unanimous, so the transcript analyses are exploratory.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
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
- •Age 18 to 75 years inclusive
- •Graves' orbitopathy graded moderate-to-severe by EUGOGO criteria
- •Active disease, clinical activity score ≥ 3 of 7
- •Rehabilitative orbital decompression anticipated after completion of glucocorticoid therapy, on the usual clinical grounds
- •Able to attend weekly infusion visits and complete follow-up to week 48
- •Written informed consent given
- •For women of childbearing potential, agreement to use effective contraception until week 24
排除标准
- •Sight-threatening disease at screening: dysthyroid optic neuropathy or corneal breakdown
- •Any other autoimmune disease requiring systemic immunosuppresion
- •Known hypersensitivity to atorvastatin or to any statin
- •Current or recent (within 3 months) use of any lipid-lowering drug
- •Any contraindication to orbital decompression
- •Any independent indication for lipid-lowering therapy: established atherosclerotic cardiovascular disease, more than one cardiovascular risk factor (diabetes mellitus, hypertension, obesity), or LDL cholesterol ≥ 190 mg/dL
- •Systemic glucocorticoid or immunosuppressive treatment for orbitopathy within the preceding 3 months
- •Previous orbital irradiation or orbital surgery
- •Alanine or aspartate aminotransferase > 3 × upper limit of normal, or creatine kinase > 5 × upper limit of normal, at screening
- •Estimated glomerular filtration rate < 30 mL/min/1.73 m²
- •Pregnancy at screening (confirmed by a negative test before randomisation) or breastfeeding
- •Concomitant treatment with a strong CYP3A4 inhibitor
- •Any condition that, in the opinion of the investigator, would prevent completion of the trial
研究组 & 干预措施
Methylprednisolone plus Atorvastatin
Experimental group recieve methylprednisolone injection 500 mg per week for six weeks followed by methylprednisolone 250 mg combined per week for following six weeks combined atorvastatin 20 mg per weeks for six months
干预措施: Atorvastatin (Drug)
Methylprednisolone only
Experimental group recieve methylprednisolone injection 500 mg per week for six weeks followed by methylprednisolone 250 mg per weeks for following six weeks
干预措施: methylprednisolone (IVMP) (Drug)
Methylprednisolone plus Atorvastatin
Experimental group recieve methylprednisolone injection 500 mg per week for six weeks followed by methylprednisolone 250 mg combined per week for following six weeks combined atorvastatin 20 mg per weeks for six months
干预措施: methylprednisolone (IVMP) (Drug)
结局指标
主要结局
Individual rectus muscle diameters
时间窗: At the first week,12th week, and 24th week from starting point of treatment
The primary outcome is measuring the rectus muscle diameters using Coronal CT, per muscle, both orbits
次要结局
- Exophthalmos, radiological(Baseline, weeks 12, 24)
- Exophthalmos, clinical(Baseline and every study visit to week 24)
- Composite ocular response(At Week 24th)
- Clinical activity score(Baseline and every study visit to week 24)
- Vertical palpebral fissure height(Baseline and every study visit to week 24)
- Change in LDL cholesterol(Baseline, weeks 12, 24)
- Orbital fat volume(Baseline, weeks 12, 24)
- Transcript levels in peripheral blood(Baseline, weeks 12, 24)
- Transcript levels in orbital tissue(At decompression 24th week)
研究者
Banu Aji Dibyasakti
Principle investigator
Gadjah Mada University