Prednisolone in Early Diffuse Systemic Sclerosis
- Conditions
- Systemic Sclerosis
- Interventions
- Drug: Placebo oral capsule; From August 2020 'no additional treatment'
- Registration Number
- NCT03708718
- Lead Sponsor
- Prof. Ariane herrick
- Brief Summary
This is a randomised placebo-controlled study of moderate dose prednisolone for 6 months in patients with early diffuse cutaneous systemic sclerosis (dcSSc). Seventy-two patients within 3 years of the onset of skin thickening will be recruited from 14 UK centres over 3 years. Co-primary end-points will be the Health Assessment Questionnaire Disability Index (HAQ-DI) and the modified Rodnan skin score (mRSS). Patients will be assessed 5 times: screening, baseline, 6 weeks, 3 and 6 months, with a code-break on exit from the study at 6 months.
Please note: From August 2020, the trial was re-started following halt due to Covid-19 as open-label. The placebo arm is the 'no treatment' arm and there is no longer a code-break at study exit.
- Detailed Description
The study is a non-commercial phase II randomised, double-blind, placebo-controlled, multi-centre study to test moderate dose prednisolone versus placebo in patients with early diffuse cutaneous systemic sclerosis (dcSSc).
Our aim is to investigate whether treatment with the steroid prednisolone is beneficial in patients with early diffuse cutaneous systemic sclerosis (also termed "scleroderma"). This is a controversial subject. Although it is very possible that prednisolone can help relieve the severe pain, itching, and disability (due to contractures and musculoskeletal involvement) of early diffuse scleroderma, doctors are often reluctant to prescribe prednisolone because of possible side effects, particularly an increased risk of serious kidney problems. Our proposed trial, treating patients with either prednisolone or placebo therapy for 6 months, should provide clinicians with a long awaited answer to the important clinical question: Can prednisolone be used as a therapy in this group of patients?
The study, funded by Arthritis Research UK, aims to determine:
1. Is moderate dose prednisolone effective in reducing pain, disability and skin thickening in patients with early diffuse scleroderma?
2. Is moderate dose prednisolone a safe therapy in patients with early diffuse scleroderma (with particular reference to kidney function)?
If the answer to both is 'yes', then prednisolone therapy will be much more widely prescribed for this patient group.
The patient population will be selected from individuals with early dcSSc, as defined by skin involvement of less than 3 years, who are considered potentially able to benefit from this treatment. Following screening, to minimise bias, eligible patients will be randomised at the baseline visit to receive either daily moderate dose prednisolone (as determined by body weight) or a matched placebo. To further eliminate subjective and unrecognised bias both the research team and patients will be blind to the randomisation. A placebo control, as opposed to an active treatment control, will be administered. This is necessary as the study treatment is adjunctive to and not a substitute for any other therapies which may be prescribed, such as immunosuppressant therapies.
Patients will attend on 5 occasions (screen, baseline, 6 weeks, 3 and 6 months). All patients will be considered off-study at the end of the 6 month visit whereupon the treatment code will be broken. At each visit a number of measurements will be taken including functional ability, degree of skin involvement (skin score), mood and kidney function. This will allow us to determine whether 'active' (prednisolone) therapy is effective and free from serious side-effects.
Please note: from August 2020, due to Covid-19 the trial was re-designed and re-started following trial halt as open-label. A placebo is no longer required. The aims, primary outcome measures and number of visits remain unchanged. However, to further mitigate the ongoing impact of Covid-19, the screen and baseline assessments may now be conducted at the same visit. Remote visits can also be carried out at 6 weeks and 6 months, if necessary.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
- Patients presenting with dcSSc with skin involvement extending to the proximal limb and/or trunk.
- Male or female age ≥ 18 years.
- Skin involvement of less than 3 years defined by patient report or clinician opinion.
- Patient is able and willing to follow the requirements of the study.
- Fully written informed consent.
- Patients with significant uncontrolled Stage 1 Hypertension (clinic BP >140/90mmHg i.e. either >140mmHg OR >90mmHg). Patients with previous hypertension which is controlled (clinic BP <140/90mmHg) for at least 4 weeks are considered eligible.
- Previous renal crisis or significant renal impairment (estimated Glomerular Filtration Rate (eGFR) < 40 ml/min).
- Patients currently on steroid therapy, or previous steroid therapy within the last 4 weeks, with the exception of inhaled steroids for respiratory diseases.
- Patients currently participating in another randomised controlled trial of an investigational agent or device, or previous participation within the last 30 days.
- Patients currently receiving an immunosuppressant or biologic therapy the dose of which has changed in the last 4 weeks prior to the baseline visit, or is likely to change during the first 3 months of study treatment.
- Patients with major myositis or inflammatory arthritis. Patients with low level myositis or inflammatory arthritis are eligible for inclusion (for example, in the case of myositis, a creatine kinase less than 4 times the upper limit of normal or myositis only demonstrable on magnetic resonance imaging).
- Female patients who are pregnant at time of screening.
- Female patients who are breastfeeding.
- Patients with significant inflammatory bowel disease as judged by the investigator.
- It is important that patients do not suddenly stop taking the study medication. Patients who do not fully understand this, will be excluded.
- Patients who are unwilling or unable to provide informed consent.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo oral capsule; From August 2020 - 'no additional treatment' Placebo oral capsule; From August 2020 'no additional treatment' The placebo will be a hard gelatine capsule filled with lactose BP and identically matched to the prednisolone capsules. The placebo will be self-administered once a day, orally with water before or after a meal. Dosing will be continuous for a total of 6 months. From August 2020 - no placebo capsule will be administered. Prednisolone Prednisolone 5 mg Prednisolone 5mg enteric-coated tablets, over-encapsulated in a hard gelatine capsule and filled with lactose BP. The prednisolone will be self-administered, orally with water before or after a meal once a day. Dosing will be continuous for a total of 6 months. The total dose prescribed will be equivalent to approximately 0.3mg/kg/day. The minimum dose prescribed will be 10mg per day (2 capsules) and a maximum of 30mg per day (6 capsules). From August 2020: The prednisolone is no longer over-encapsulated. Prednisolone 5mg enteric-coated tablets will be prescribed and taken as above.
- Primary Outcome Measures
Name Time Method Health Assessment Questionnaire Disability Index (HAQ-DI) Baseline to 3 months The mean difference in HAQ-DI at 3 months
modified Rodnan Skin Score (mRSS) Baseline to 3 months The difference in mRSS at 3 months
- Secondary Outcome Measures
Name Time Method Health related quality of life - Assessed by Questionnaire Baseline to 6 weeks, 3 months and 6 months Short Form (36) Health Survey
Pain and disability - Assessed by Questionnaire Baseline to 6 weeks, 3 months and 6 months Assessment of Arthritis Index
Fatigue - Assessed by Questionnaire Baseline to 6 weeks, 3 months and 6 months Functional Assessment of Chronic Illness Therapy (FACIT)
Health related quality of Life - Assessed by Questionnaire Baseline to 6 weeks, 3 months and 6 months EuroQol 5 Dimensions
Hand function - Assessed by Questionnaire Baseline to 6 weeks, 3 months and 6 months Cochin Hand Function
Assessment of pain - Clinician assessment Baseline to 6 weeks, 3 months and 6 months Joint Count: The number of tender or swollen joints are assessed from 14 anatomical sites (both left and right side) and recorded out of a total of 28 (14 sites, left and right side) tender joints and 28 swollen joints
Quality of life and functional ability - Assessed by Questionnaire Baseline to 6 weeks and 6 months HAQ-DI
Functional ability - Assessed by Questionnaire Baseline to 6 weeks, 3 months and 6 months 11-point Scleroderma Functional Index
Pain associated with itch - Assessed by Questionnaire Baseline to 6 weeks, 3 months and 6 months Assessment of Pruritus
Pain and disability Baseline to 6 weeks, 3 months and 6 months Assessment in percentage change of mRSS
Anxiety and depression - Assessed by questionnaire Baseline to 6 weeks, 3 months and 6 months Hospital Anxiety and Depression Scale (HADS) . This questionnaire has 14 questions, each with 4 options designed to assess aspects of mental health
Trial Locations
- Locations (14)
Aintree University Hospitals NHS Foundation Trust
🇬🇧Liverpool, Merseyside, United Kingdom
Ninewells Hospital and Medical School - NHS Tayside
🇬🇧Dundee, United Kingdom
Salford Royal NHS Foundation Trust
🇬🇧Salford, Greater Manchester, United Kingdom
The Dudley Group NHS Foundation Trust
🇬🇧Dudley, West Midlands, United Kingdom
Aberdeen Royal Infirmary - NHS Grampian
🇬🇧Aberdeen, Aberdeenshire, United Kingdom
Royal National Hospital For Rheumatic Diseases - Royal United Hospitals Bath NHS Foundation Trust
🇬🇧Bath, Somerset, United Kingdom
Southmead Hospital Bristol - North Bristol NHS Trust
🇬🇧Bristol, United Kingdom
Glasgow Royal Infirmary -
🇬🇧Glasgow, Lanarkshire, United Kingdom
Queen's Medical Centre - Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, Nottinghamshire, United Kingdom
Royal Hallamshire Hospital - Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, South Yorkshire, United Kingdom
Freeman Hospital - The Newcastle upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle Upon Tyne, Tyne And Wear, United Kingdom
Addenbrooke's Hospital - Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Leeds Institute of Rheumatic and Musculoskeletal Medicine
🇬🇧Leeds, West Yorkshire, United Kingdom
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom