A Phase 1/2 interventional study of Mesenchymal stromal cells and Placebo in Systemic Sclerosis and Digital Ulcer, sponsored by UMC Utrecht. Recruiting at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-09-10.
Sponsored by UMC Utrecht · Phase 1/2, Interventional, and Treatment
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.
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
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.
610 studies on the registry are indexed under Scleroderma, Systemic; 218 are open to participants now.
This study's planned enrollment of 20 is below the median of 37 across 446 interventional studies indexed under Scleroderma, Systemic.
Browse Scleroderma, Systemic studies →UMC Utrecht is the lead sponsor of 364 studies on the registry; 82 are open to participants now.
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At least one active digital ulcer (painful area, >2 mm in diameter with visible depth and loss of dermis) to intravenous prostacyclins
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Intramuscular injection of mesenchymal stromal cells (50 million allogeneic MSCs in 0.9% NaCl and 10% human serum albumin).
Drug: Mesenchymal stromal cells
Intramuscular injection of placebo (NaCl 0.9% + 10% human serum albumin)
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).
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).
Toxicity of the treatment
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.
Time frame: 12 weeks after MSC administration
Serious adverse events
Any treatment-related serious adverse events (SAE) defined as events leading to hospitalization, death, or persistent or significant disability. To establish the presence or absence of a causal relationship, the World Health Organisation guidelines for pharmacovigilance will be followed.
Time frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration
Change in perceived pain based on the Numerical Rating Scale
Change in pain as assessed using the Numerical Rating Scale,
Time frame: 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)
Change in pain as assessed using the digital ulcer visual analogue scale (part of the S-HAQ).
Time frame: 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)
Change in pain as assessed using the pain VAS (S-HAQ), use of analgesics.
Time frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration
Change in perceived pain based on the use of analgesics.
Change in pain as assessed by analyzing the use of analgesics.
Time frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration
Quality of life - SF-36
SF-36 questionnaire.
Time frame: 12, 24 and 52 weeks after MSC administration
Quality of life - Euroqol
EuroQol questionnaire
Time frame: 12, 24 and 52 weeks after MSC administration
Disability
Assessed with the HAQ-DI questionnaire.
Time frame: 12, 24 and 52 weeks after MSC administration
Hand function
Cochin Hand Function Score
Time frame: 12, 24 and 52 weeks after MSC administration
Number (and change in number) of digital ulcers
Time frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration
Healing of digital ulcers
Healing of ulcers is defined as complete epithelialization, regardless of residual pain. This will be established using sequential pictures in addition to the clinical examination.
Time frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration
Ulcer size
Using sequential pictures, ulcer area and circumference will be measured.
Time frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration
Time to healing of digital ulcers
Time frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration
Need to alter medication regime
The need to alter the medication regime as determined by the patient's attending rheumatologist.
Time frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration
Modified Rodnan Skin Score
Time frame: 12, 24 and 52 weeks after MSC administration
Severity of Raynaud's symptoms
Raynaud Condition Score
Time frame: 12 , 24 and 52 weeks after MSC administration
Changes in capillary morphology and architecture
as visualized with video-assisted nailfold capillaroscopy by a trained investigator. The images will be scored by a certified rheumatologist and a trained investigator.
Time frame: 2, 12, 24 weeks and 52 weeks after MSC administration
Changes in laboratory parameters
A range of haematological and chemical parameters will be measured for safety assessment. Additionally, serum, plasma and peripheral blood mononuclear cells will be collected and stored for analysis at a later time point. Samples will be analysed and used to assess markers for endothelial activation and injury, proangiogenic factors, inflammation and oxidative stress. The presence of HLA-antibodies will be determined as well.
Time frame: 48 hours, 2, 4, 8, 12 weeks after MSC administration
Changes in circulating cell populations
Circulating cell populations will be studied by immunofluorescence labelling and analysis using fluorescence assisted cell sorting (FACS Canto machine).
Time frame: 48 hours, 2, 4, 8, 12 weeks after MSC administration
Plan to share: Undecided
Started Oct 2021 (actual). Primary completion is estimated for Nov 2026, 60 months after the start.
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