NCT03211793

Mesenchymal Stromal Cells as Treatment for Digital Ulcers in Systemic Sclerosis

Mesenchymal Stromal Cells for Angiogenesis and Neovascularisation in Digital Ulcers of Systemic Sclerosis: the MANUS Trial

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: UMC Utrecht · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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 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. 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.

Conditions

• Systemic Sclerosis
• Digital Ulcer

Interventions

Type	Name	Description
DRUG	Mesenchymal stromal cells	8 intramuscular injections at designated sites in the hand/forearm muscles of the most affected side. Blinded syringes will be used. Injections will be administered by an experienced clinician (plastic surgeon or hand surgeon).
OTHER	Placebo	8 intramuscular injections at designated sites in the hand/forearm muscles of the most affected side. Blinded syringes will be used. Injections will be administered by an experienced clinician (plastic surgeon or hand surgeon).

Timeline

• Start date: 2021-10-06
• Primary completion: 2026-11-01
• Completion: 2026-11-01
• First posted: 2017-07-07
• Last updated: 2025-09-10

Locations

1 site across 1 country: Netherlands