Mesenchymal Stromal Cells for Angiogenesis and Neovascularisation in Digital Ulcers of Systemic Sclerosis: the MANUS Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- UMC Utrecht
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Toxicity of the treatment
研究概览
简要总结
The MANUS Trial aims to examine the safety, feasibility and potential efficacy of intramuscularly injected allogeneic mesenchymal stromal cells as treatment for digital ulcers of systemic sclerosis.
详细描述
The MANUS Trial is a randomized double-blind, placebo-controlled clinical trial. Patients with systemic sclerosis (SSc) and digital ischemia with intractable ischemic digital ulcers refractory to conventional treatments are eligible to participate.
20 participants will be randomised (1:1) to undergo intramuscular injection (8 sites) of allogeneic bone marrow derived mesenchymal stromal cells (BM-MSC) (45-50*10^6) or placebo in the most affected limb.
Main study parameters/endpoints: The primary outcome is the toxicity of the treatment at 12 weeks after MSC administration, defined as
- Local toxicity, including signs of local inflammation (swelling, warmth, impairment of function), worsening of ulcers or new ulcers or hematomas after MSC administration
- Other adverse events, graded according to the Common Terminology Criteria for Adverse Events version 4.0, expressed as maximum grade toxicity per organ system.
Secondary outcome measures are: number of serious adverse events, pain and disability parameters; healing, time to healing and reduction of new ischemic digital ulcers; modified Rodnan skin score; Scleroderma Health Assessment Questionnaire (S-HAQ) including visual analogue scales (VAS) for scleroderma-specific symptoms; Quality-of-life (SF-36, EuroQol (EQ-5D); Cochin hand function score. We will also evaluate changes in capillary morphology and architecture using capillaroscopy; biochemical parameters; markers for endothelial activation and injury, inflammation, oxidative stress, circulating cells including endothelial cells, hematopoietic and endothelial progenitor cells, cytokines and growth factors, immunological responses. Follow-up visits will be scheduled at 48 hours and 2, 4, 8, 12, 24 and 52 weeks post-treatment.
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)
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
- •Established diagnosis of SSc according to the 2013 ACR/EULAR criteria
- •At least one active digital ulcer (painful area, >2 mm in diameter with visible depth and loss of dermis) refractory to intravenous prostacyclins
- •'Refractory to prostacyclins' is defined as
- •Worsening of ulcer(s) within 1 month after prostacyclins iv
- •No improvement of ulcer(s) after 2 months after prostacyclins iv, as judged by the referring physician
- •Recurrence of exactly the same ulcer(s) (same location) within 3 months after prostacyclins iv
- •Written informed consent
排除标准
- •Ulcer with underlying calcinosis (ruled out by X-ray prior to screening/inclusion)
- •History of neoplasm or malignancy in the past 10 years
- •Pregnancy or unwillingness to use adequate contraception during study
- •Serious known concomitant disease with life expectancy <1 year
- •Uncontrolled hypertension
- •Uncontrolled acute or chronic infection with systemic symptoms (e.g. fever)
- •Follow-up impossible
研究组 & 干预措施
Placebo injections
Intramuscular injection of placebo (NaCl 0.9% + 10% human serum albumin)
干预措施: Placebo (Other)
MSC injections
Intramuscular injection of mesenchymal stromal cells (50 million allogeneic MSCs in 0.9% NaCl and 10% human serum albumin).
干预措施: Mesenchymal stromal cells (Drug)
结局指标
主要结局
Toxicity of the treatment
时间窗: 12 weeks after MSC administration
Toxicity of the treatment is defined as 1. Local toxicity, including signs of local inflammation (swelling, warmth, impairment of function), worsening of ulcers or new ulcers or hematomas after MSC administration 2. Other adverse events, graded according to the Common Terminology Criteria for Adverse Events version 4.0, expressed as maximum grade toxicity per organ system.
次要结局
- Serious adverse events(48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration)
- Change in perceived pain based on the Numerical Rating Scale(48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration)
- Quality of life - SF-36(12, 24 and 52 weeks after MSC administration)
- Quality of life - Euroqol(12, 24 and 52 weeks after MSC administration)
- Disability(12, 24 and 52 weeks after MSC administration)
- Hand function(12, 24 and 52 weeks after MSC administration)
- Number (and change in number) of digital ulcers(48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration)
- Healing of digital ulcers(48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration)
- Ulcer size(48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration)
- Time to healing of digital ulcers(48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration)
- Change in perceived pain based on the digital ulcer visual analogue scale (part of the S-HAQ)(48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration)
- Change in perceived pain based on the pain VAS ( part of the S-HAQ)(48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration)
- Change in perceived pain based on the use of analgesics.(48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration)
- Need to alter medication regime(48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration)
- Modified Rodnan Skin Score(12, 24 and 52 weeks after MSC administration)
- Severity of Raynaud's symptoms(12 , 24 and 52 weeks after MSC administration)
- Changes in capillary morphology and architecture(2, 12, 24 weeks and 52 weeks after MSC administration)
- Changes in laboratory parameters(48 hours, 2, 4, 8, 12 weeks after MSC administration)
- Changes in circulating cell populations(48 hours, 2, 4, 8, 12 weeks after MSC administration)