Mesenchymal Stromal Cells as Treatment for Digital Ulcers in Systemic Sclerosis

NCT03211793 | Recruiting Phase 1 DMC

• 2 other identifiers: MANUS2015-000168-32
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Systemic Sclerosis; Digital Ulcer

Keywords

systemic sclerosis; scleroderma; digital ulcer; vasculopathy; mesenchymal stromal cell; mesenchymal stem cell

Outcome Measures

Primary Outcomes (1)

• 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.

  12 weeks after MSC administration

Secondary Outcomes (19)

• 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

• 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

Study Arms (2)

MSC injections

EXPERIMENTAL

Intramuscular injection of mesenchymal stromal cells (50 million allogeneic MSCs in 0.9% NaCl and 10% human serum albumin).

Drug: Mesenchymal stromal cells

Placebo injections

PLACEBO COMPARATOR

Intramuscular injection of placebo (NaCl 0.9% + 10% human serum albumin)

Other: Placebo

Interventions

Mesenchymal stromal cells DRUG

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).

MSC injections

Placebo OTHER

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).

Placebo injections

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UMC Utrecht: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

RECRUITING

Related Publications (1)

• van Rhijn-Brouwer FCC, Gremmels H, Fledderus JO, Schuurman AH, Bonte-Mineur F, Vonk MC, Voskuyl AE, de Vries-Bouwstra JK, Coert JH, Radstake TRDJ, van Laar JM, Verhaar MC; MANUS Study Group. A randomised placebo-controlled double-blind trial to assess the safety of intramuscular administration of allogeneic mesenchymal stromal cells for digital ulcers in systemic sclerosis: the MANUS Trial protocol. BMJ Open. 2018 Aug 20;8(8):e020479. doi: 10.1136/bmjopen-2017-020479.

  PMID: 30127049 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic; digital ulcers; Scleroderma, Diffuse; Vascular Diseases

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Cardiovascular Diseases

Study Officials

• Marianne Verhaar, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Femke van Rhijn, MD

CONTACT

0031887557329; f.c.c.brouwer-3@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: prof. dr.

Study Record Dates

• First Submitted: April 27, 2017
• First Posted: July 7, 2017
• Study Start: October 6, 2021
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: September 10, 2025

Record last verified: 2025-09

Locations

NL (1)