MINIMISE-Pilot
Research type
Research Study
Full title
A randomised prospective open label pilot trial comparing mycophenolate mofetil (MMF) with no immunosuppression in adults with limited cutaneous systemic sclerosis MINIMISE-Pilot (Mycophenolate in limited cutaneous systemic sclerosis)
IRAS ID
275187
Contact name
Christopher Denton
Contact email
Sponsor organisation
University College London Comprehensive Clinical Trial Unit
Eudract number
2019-004139-21
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 4 months, 1 days
Research summary
Summary of Research
Systemic sclerosis or scleroderma is an autoimmune condition that causes thickening and hardening of the skin, but can also affect internal organs.
There are two major subsets of scleroderma: the limited cutaneous systemic sclerosis (lcSSc) that usually affects the skin of the face, neck, lower legs or lower arms, but can also lead to internal organ complications, and the diffuse cutaneous systemic sclerosis (dcSSc), that may affect blood circulation and internal organs, as well as the skin.
To date there is no drug that has been definitively proven to cure or modify the course of scleroderma. However, there is emerging evidence that immunosuppression and specifically mycophenolate mofetil (MMF) may be beneficial in lcSSc. The MINIMISE-Pilot trial would be an important first step to evaluate the risk and potential benefit to this disease group. MMF as the intervention of choice is both appropriate and timely, as it has been routinely used in the management of dcSSc.
The MINIMISE-Pilot trial aims to explore whether the immunosuppressive agent MMF at a target dose of 2g daily can slow down disease progression in patients with lcSSc compared to the current standard of care alone. This pilot trial will also provide critical information for the development of a future large trial that could potentially transform lcSSc patient management. This is an open label randomised prospective trial that will recruit 120 participants aged 18 or over across 13 sites in the UK. The trial will involve five (5) clinic visits which are expected to be carried out at the same time of the participants routine hospital appointment. In addition, they will receive four (4) routine telephone calls in between their clinic visits. Participants are expected to be followed up for a minimum of 48 weeks or a maximum of 96 weeks.Summary of Results
Systemic sclerosis (SSc), also known as scleroderma, is a serious multi-system inflammatory disease characterized by dysregulated autoimmunity, inflammation, vascular damage, and fibrosis, leading to disability and organ failure. Although rare, SSc has high mortality and morbidity rates.
Patients with SSc face a substantial clinical impact, with more than half ultimately dying from SSc-related complications. This outcome is worse than many malignancies and is particularly poor for a rheumatological disease. In addition to lethal complications, there is a significant non-lethal disease burden, including digital ulceration and musculoskeletal issues.Purpose of the Study: This study aimed to evaluate the feasibility of recruiting patients and the viability of clinical endpoints for a future definitive trial. The ultimate goal was to determine if patients with Limited Cutaneous Systemic Sclerosis on Mycophenolate Mofetil have a lower rate of developing significant complications compared to those not on immunosuppression.
Study Design: The MINIMISE-Pilot was a multicentre randomised prospective open-label external pilot trial and took place in the UK. It aimed to recruit 120 participants however only 43 participants with Limited Cutaneous Systemic Sclerosis were recruited. Participants were randomly assigned to receive either Mycophenolate Mofetil or no immunosuppression, in addition to standard care for Systemic Sclerosis-related symptoms.
Reason for Termination: The study was terminated early by the funder due to recruitment being below the level that would suggest feasibility of a future full trial using a similar study design. As a feasibility pilot the goal of the MINIMISE-Pilot had been achieved.
Number of Participants: A total of 43 participants were enrolled in the study before it was terminated.
Results:
• No participants reported any any clinical endpoints at any visit.
• The data indicate a high consent rate of 84.3%, with 43 out of 51 eligible patients consenting to participate.
• Serious Adverse Events (SAEs): Three patients (7%) reported at least one SAE. This included two patients (9%) in the control group and one patient (5%) in the MMF group. The SAEs reported were gastrointestinal disorders (1 on MMF), injury and procedural complications (1 on control), and musculoskeletal and connective tissue disorders (1 on control).
• Adherence to MMF: Adherence to MMF was generally high, with 19 participants (95%) being 100% adherent at Week 1, decreasing to 9 participants (64%) at Week 24.
• Baseline Characteristics: The average age of participants was 56.56 years, with a nearly equal distribution between the control and MMF groups. Most participants were female (83.72%) and of White British ethnicity (81.40%).Impact of Termination: The early termination of the study means that definitive conclusions about the effectiveness and safety of MMF in lcSSc cannot be drawn. However, the data collected may inform the design of a future definitive trial.
Next Steps: Further analysis of the collected data will be conducted to guide the design of a larger, double-blind placebo-controlled trial. This future trial informed by the results and experience of MINIMISE-Pilot will aim to provide more conclusive evidence on the potential benefits of MMF for lcSSc patients.
REC name
London - Central Research Ethics Committee
REC reference
20/LO/0352
Date of REC Opinion
2 Apr 2020
REC opinion
Favourable Opinion