Mesenchymal Stromal Cells as Treatment for Digital Ulcers in Systemic Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 December 2023
• Main ID: NCT03211793
• Date of registration: 27/04/2017
• Prospective Registration: Yes
• Primary sponsor: UMC Utrecht
• Public title: Mesenchymal Stromal Cells as Treatment for Digital Ulcers in Systemic Sclerosis MANUS
• Scientific title: Mesenchymal Stromal Cells for Angiogenesis and Neovascularisation in Digital Ulcers of Systemic Sclerosis: the MANUS Trial
• Date of first enrolment: October 6, 2021
• Target sample size: 20
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03211793
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

Netherlands

Contacts

• Name: Femke van Rhijn, MD

• Name: Marianne Verhaar, MD, PhD
• Affiliation: UMC Utrecht

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Digital Ulcer

Systemic Sclerosis

Intervention(s)

Drug: Mesenchymal stromal cells

Other: Placebo

Primary Outcome(s)

Toxicity of the treatment [Time Frame: 12 weeks after MSC administration]

Secondary Outcome(s)

Change in perceived pain based on the pain VAS ( part of the S-HAQ) [Time Frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration]

Quality of life - SF-36 [Time Frame: 12, 24 and 52 weeks after MSC administration]

Ulcer size [Time Frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration]

Changes in laboratory parameters [Time Frame: 48 hours, 2, 4, 8, 12 weeks after MSC administration]

Disability [Time Frame: 12, 24 and 52 weeks after MSC administration]

Hand function [Time Frame: 12, 24 and 52 weeks after MSC administration]

Need to alter medication regime [Time Frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration]

Changes in circulating cell populations [Time Frame: 48 hours, 2, 4, 8, 12 weeks after MSC administration]

Severity of Raynaud's symptoms [Time Frame: 12 , 24 and 52 weeks after MSC administration]

Quality of life - Euroqol [Time Frame: 12, 24 and 52 weeks after MSC administration]

Serious adverse events [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. [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]

Number (and change in number) of digital ulcers [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 [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]

Change in perceived pain based on 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]

Healing of digital ulcers [Time Frame: 48 hours, 2, 4, 8, 12, 24 weeks and 52 weeks after MSC administration]

Changes in capillary morphology and architecture [Time Frame: 2, 12, 24 weeks and 52 weeks after MSC administration]

Secondary ID(s)

MANUS

2015-000168-32

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

ZonMw: The Netherlands Organisation for Health Research and Development