Randomized Placebo-controlled Trial of the Safety and Efficacy of Topical Sodium Metabisulfite for the Treatment of Calcinosis in Patients With Systemic Sclerosis.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- To assess the safety and tolerability of using topical 25% SM applied twice daily in SSc patients with calcinosis affecting the hands
研究概览
简要总结
This prospective placebo-controlled trial will enroll 20 patients with SSc and at least one calcinotic lesion of the hands that is palpable on physical examination and measurable on hand radiographs. Each subject will undergo a screening evaluation 1 month before treatment with the study drug is initiated. Each subject will be instructed to blindly self-apply either topical 25% sodium metabisulfite or placebo cream twice daily. In-person follow-up evaluations will be performed after 4-months, with monthly telehealth follow-up visits to ensure adherence and arrange study drug refill deliveries.
详细描述
- Background:
Calcinosis cutis is the deposition of calcium in the skin and subcutaneous tissues. It is a common and debilitating manifestation of systemic sclerosis (SSc), affecting 1 in 4 of these patients over the course of their disease. Calcinosis in SSc occurs most frequently in the hands, particularly the fingers, and within the fingers, most commonly in the thumbs or index of the dominant hand. Calcinosis in SSc can cause pain, soft tissue swelling around the calcium deposits, ulcers with superimposed infection, or deformities, leading to significant impact on quality of life.
Treatment for calcinosis cutis is often difficult and unsuccessful and remains an unmet need in patients with SSc. Evidence mainly comes from small retrospective studies, case series, and case reports, since no large, prospective randomized controlled trials have been conducted. The response to various agents, such as topical or oral aluminum hydroxide, topical or intralesional sodium thiosulfate, intralesional corticosteroids, calcium-channel blockers, minocycline, bisphosphonates, and surgical excision has remained largely unsatisfactory.
Topical, intralesional and intravenous (IV) sodium thiosulfate have been studied as treatments for disorders of cutaneous calcium deposition. The mechanism of sodium thiosulfate in the treatment of calcium-related disorders is thought to be multifactorial. It is believed to act by transforming calcium into calcium thiosulfate salts, thus increasing calcium solubility. In addition, it may increase the production of hydrogen sulfide, which has vasodilatory, antioxidant and anti-inflammatory properties, and may cause direct inhibition of vascular calcifications.
Sodium metabisulfite (SM) is an inorganic compound used as a disinfectant, antioxidant and preserving agent that, when reacting with oxygen, becomes sodium sulfate, a metabolite of sodium thiosulfate that has a similar ability to inhibit calcium oxalate agglomeration and calcium stone formation. In 2016, topical 25% SM was used for the first time in four patients with dystrophic calcinosis cutis (one with SSc, two with dermatomyositis and one with radio-dermatitis after breast cancer), showing significant decrease in size, erythema, and pain. The authors hypothesized that topical SM may dissolve calcium deposits and promote local vasodilation and wound healing. Since then, topical sodium metabisulfite use has been reported as an inexpensive, safe and promising new agent for the treatment of calcinosis cutis.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The research products will be prepared in pediatric cold cream (water in oil emulsion) at a concentration of 25% or placebo, with identical packing and labeling, each identified by an exclusive number ID which will be assigned by a researcher not involved with the trial.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent
- •Age > 18 years of age
- •Diagnosis of limited or diffuse cutaneous systemic sclerosis (SSc) according to the revised 2013 ACR/EULAR classification criteria for SSc (21)
- •Radiological and physical examination evidence of at least one subcutaneous calcium deposition in the hands that is clinically apparent as part of routine clinical care.
- •If female of childbearing potential, the patient must have a negative pregnancy test at screening and baseline visits
- •Oral corticosteroids (≤ 5 mg/day of prednisone or equivalent) and NSAIDs are permitted if the patient is on a stable dose regimen for ≥ 2 weeks prior to screening and throughout the study
- •Oral CCB, alpha-1-antagonists, ACE-inhibitors, angiotensin receptor blockers, and protein-pump inhibitors are permitted if the doses are stable for 4 weeks prior to screening and throughout the study.
排除标准
- •Rheumatic disease other than SSc
- •Allergy to sodium metabisulfite
- •Pregnant or nursing women
- •Concurrent malignancy except non-melanoma skin cancers
- •Patients receiving bisphosphonates, warfarin, colchicine, minocycline, intravenous immunoglobulins, or biological agents specifically abatacept or rituximab within 4 weeks of screening
- •Patients receiving local treatments for calcinosis of the hands including surgical removal or intralesional steroid injections within 12 weeks of screening or throughout the study.
- •Patients who have participated in another clinical trial of an investigative agent within 30 days of screening (or 5 half-lives of the investigational drug, whichever is longer)
- •Patients with a history of drug or alcohol abuse within 6 months of screening
- •Any medical condition that, in the opinion of the investigator, might interfere with the subject's participation in the study or poses an added risk for the subject
- •Inability to comply with study and follow-up procedures
研究组 & 干预措施
Sodium metabisulfite cream
Sodium metabisulfite prepared in pediatric cold cream (water in oil emulsion) at a concentration of 25% to be applied on calcinosis topically twice daily.
干预措施: Topical 25% sodium metabisulfite (SM) in pediatric cold cream (Drug)
Placebo cream
Pediatric cold cream (water in oil emulsion) to be applied on calcinosis topically twice daily.
干预措施: Placebo (Drug)
结局指标
主要结局
To assess the safety and tolerability of using topical 25% SM applied twice daily in SSc patients with calcinosis affecting the hands
时间窗: 4 months
The primary assessment of safety will be the development of adverse events. Any significant changes to the subject's medical condition, physical examination, and concomitant medications will be documented throughout the course of the study. Any untoward medical experience will be recorded as an adverse event.
To assess the efficacy of topical 25% SM versus placebo in stabilizing the calcinosis burden or reducing the radiographic progression of calcinosis over four months.
时间窗: 4 months
Radiograph of the hands will be scored using the SCTC radiographic calcinosis scroing system
次要结局
- To assess the effect of topical 25% SM on the change in the Mawdsley Calcinosis Questionnaire, and patient and physician assessment of calcinosis severity over four months.(4 months)
- To assess the effect of topical 25% SM on the change in size of calcinosis on ultrasound.(4 months)
- To assess the presence of markers of vascular damage and inflammation by tape stripping in SSc patients with calcinosis.(4 months)
研究者
Antonia Valenzuela
MD, MS, Assistant Professor at Pontificia Universidad Católica de Chile
Pontificia Universidad Catolica de Chile