An Open-label Study of Sodium Thiosulfate for Treatment of Calcinosis Associated With Juvenile and Adult Dermatomyositis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change in Calcinosis Activity Visual Analogue Scale Score
研究概览
简要总结
Background:
Dermatomyositis (DM) and juvenile dermatomyositis (JDM) cause inflammation in the muscles. People with DM and JDM can develop calcium deposits in places they should not, known as calcinosis. Calcinosis can be painful and cause disabilities and other problems. Researchers want to learn more about calcinosis to find treatments for it.
Objective:
To test if sodium thiosulfate (STS) can treat people with DM with calcinosis.
Eligibility:
People ages 7 and older who have moderate or severe calcinosis. They must have stable DM and calcium deposits in the torso or at least 2 limbs.
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Muscle strength and function tests
- Blood and urine tests
Participants will have several visits:
- 7-day pre-treatment visit about 10 weeks before starting STS
- Treatment visits over 10 weeks. They will get STS 3 times a week through IV infusion. They may be hospitalized the whole time. If they tolerate the drug, they may be discharged at certain times. During these times, they will return for the infusions.
- 3- to 5-day post-treatment visits 24 weeks and 62 weeks after starting STS.
Visits may include repeats of screening tests and:
- Questionnaires
- Scans: They lie in a machine that takes pictures of the body. They may be injected with a radioactive agent.
- Durometry: A small instrument applies pressure on the skin or exposed calcinosis.
- Measurements of blood flow in the arms and fingernail blood vessels
- Photographs of the skin
- Kidney ultrasound
- Tests of kidney function
- Calcinosis aspiration: A needle placed into areas of calcinosis removes liquid.
详细描述
Calcinosis, a serious complication of dermatomyositis, involves deposition of calcium (carbonate apatite) in soft tissue, and can result in negative impacts on quality of life and physical function. To date, there are no known effective therapies that are approved for the treatment of dermatomyositis-associated calcinosis, and there is no consensus within the medical community on the optimum treatment strategy for this often-debilitating condition.
A few reports in the literature describe treatment successes with a variety of therapeutics; however, these data are from anecdotal reports or case series and thus provide limited scientific evidence of effectiveness. Recently published reports as well as personal observations within our group have suggested that intravenous sodium thiosulfate treatment may benefit calcinosis patients. In order to gather more robust data on the utility of this medication in the treatment of calcinosis associated with adult and juvenile dermatomyositis, we propose to evaluate its effects in the context of a prospective clinical trial.
We plan to enroll participants at a single center into a single-arm, open-label study, with the overall objective of evaluating the efficacy and safety of intravenous sodium thiosulfate use in patients with moderate to severe extensive calcinosis associated with juvenile and adult dermatomyositis.
The study will enroll a maximum of 18 participants over 4 years into the full study, but up to 250 patients may screen for study entry. Eligible patients will be age 7 or older, and will have extensive calcinosis (defined as calcinosis involving the torso or 2 extremities) and moderate to severe calcinosis (indicated by a calcinosis activity visual analogue scale score of greater than or equal to 3.5 cm out of 10 cm).
Two separate evaluations performed at the NIH prior to initiation of therapy will be used as baseline data to compare in a pairwise manner to the change in assessments following treatment with sodium thiosulfate, with all other medications remaining stable. Study treatment will be 16 g/m2 sodium thiosulfate administered 3 times weekly over a period of 10 weeks at the NIH. Subjects who complete 10 weeks of treatment or reach the primary end point by week 6 will be considered completers. Following the treatment period, all participants will return to the NIH for evaluations at weeks 24 and 62.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 7 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Treatment
Participants received intravenous sodium thiosulfate 16 g/m^2 three times weekly for 10 weeks
干预措施: Sodium Thiosulfate (Drug)
结局指标
主要结局
Change in Calcinosis Activity Visual Analogue Scale Score
时间窗: Week 10 minus week 0 (on therapy) and week 0 minus week -10 (baseline)
Calcinosis activity is defined by the metabolic activity and the inflammation associated with calcinosis. In evaluating calcinosis activity, the study physicians take into account the change in extent of calcinosis and the location of calcinosis lesions, the consistency and texture of calcinosis lesions, the presence of erythema surrounding calcinosis lesion, and any pain associated with the calcinosis lesions. A 10 cm visual analogue scale (VAS) was scored by a physician with a vertical line on the scale marking calcinosis activity where 0 cm indicates no evidence of calcinosis, and 10 cm mark indicates severe calcinosis activity. The change in calcinosis activity VAS score from week 0 to week 10 on therapy was compared to the change in calcinosis activity VAS score from week -10 to week 0 on baseline therapy. The baseline score was calculated by taking the week 0 score minus the week -10 score. The on therapy score was calculated by taking the week 10 score minus the week 0 score.
次要结局
- Change in Quality of Life Measured by the Child Health Questionnaire-Parent Form 50 (CHQ-PF50): Physical Function Domain(Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment))
- Change in Quality of Life Measured by the 36-Item Short Form Health Survey (SF-36) Score: General Health Domain(Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment))
- Improvement of Calcinosis Lesions Measured by the Change in Mawdsley Calcinosis Questionnaire (MCQ) Score(Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment))
- Change in Quality of Life Measured by Skindex-29 Score(Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment))
- Change in Muscle Strength Over Time Measured by Manual Muscle Test-8 (MMT-8) Score(Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment))
- Change in Muscle Strength Over Time Measured by Quantitative Muscle Assessment (QMA): Hip Abductor Muscle(Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment))
- Change in Myositis Activity Measured by Physician Global Activity (PGA)(Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment))
- Change in Myositis Damage Measured by Physician Global Damage (PGD)(Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment))
- Change in Total Percent Body Surface Area (BSA) Involved With Calcinosis(Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment))