Prednisolone in Early Diffuse Systemic Sclerosis

Systemic Sclerosis Clinical Trial

— PRedSS  

Official title:

A Phase II Randomised Study of Oral Prednisolone in Early Diffuse Cutaneous Systemic Sclerosis (Initially Double-blind, Then Switched to Open-label Because of Covid-19)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03708718
• Other study ID #: 119220
• Status: Completed
• Phase: Phase 2
• Start date: December 21, 2017
• Est. completion date: May 27, 2021

Study information

• Verified date: July 2021
• Source: University of Manchester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: May 27, 2021
• Est. primary completion date: March 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients presenting with dcSSc with skin involvement extending to the proximal limb and/or trunk.

2. Male or female age = 18 years.

3. Skin involvement of less than 3 years defined by patient report or clinician opinion.

4. Patient is able and willing to follow the requirements of the study.

5. Fully written informed consent.

Exclusion Criteria:

1. 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.

2. Previous renal crisis or significant renal impairment (estimated Glomerular Filtration Rate (eGFR) < 40 ml/min).

3. Patients currently on steroid therapy, or previous steroid therapy within the last 4 weeks, with the exception of inhaled steroids for respiratory diseases.

4. Patients currently participating in another randomised controlled trial of an investigational agent or device, or previous participation within the last 30 days.

5. 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.

6. 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).

7. Female patients who are pregnant at time of screening.

8. Female patients who are breastfeeding.

9. Patients with significant inflammatory bowel disease as judged by the investigator.

10. It is important that patients do not suddenly stop taking the study medication. Patients who do not fully understand this, will be excluded.

11. Patients who are unwilling or unable to provide informed consent.

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Drug:
• Prednisolone 5 mg
5mg prednisolone, once a day for 6 months
• Placebo oral capsule; From August 2020 'no additional treatment'
Matched placebo capsule, once a day for 6 months; From August 2020 - no additional treatment above standard of care medication

Locations

Country	Name	City	State
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	Addenbrooke's Hospital - Cambridge University Hospitals NHS Foundation Trust	Cambridge	Cambridgeshire
United Kingdom	The Dudley Group NHS Foundation Trust	Dudley	West Midlands
United Kingdom	Ninewells Hospital and Medical School - NHS Tayside	Dundee
United Kingdom	Glasgow Royal Infirmary -	Glasgow	Lanarkshire
United Kingdom	Leeds Institute of Rheumatic and Musculoskeletal Medicine	Leeds	West Yorkshire
United Kingdom	Aintree University Hospitals NHS Foundation Trust	Liverpool	Merseyside
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	Freeman Hospital - The Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne	Tyne And Wear
United Kingdom	Queen's Medical Centre - Nottingham University Hospitals NHS Trust	Nottingham	Nottinghamshire
United Kingdom	Salford Royal NHS Foundation Trust	Salford	Greater Manchester
United Kingdom	Royal Hallamshire Hospital - Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield	South Yorkshire

Sponsors (2)

Lead Sponsor	Collaborator
Prof. Ariane herrick	Versus Arthritis

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Health Assessment Questionnaire Disability Index (HAQ-DI)	The mean difference in HAQ-DI at 3 months	Baseline to 3 months
Primary	modified Rodnan Skin Score (mRSS)	The difference in mRSS at 3 months	Baseline to 3 months
Secondary	Quality of life and functional ability - Assessed by Questionnaire	HAQ-DI	Baseline to 6 weeks and 6 months
Secondary	Pain and disability	Skin involvement as measured by the mRSS	Baseline to 6 weeks and 6 months
Secondary	Functional ability - Assessed by Questionnaire	11-point Scleroderma Functional Index	Baseline to 6 weeks, 3 months and 6 months
Secondary	Pain associated with itch - Assessed by Questionnaire	Assessment of Pruritus	Baseline to 6 weeks, 3 months and 6 months
Secondary	Hand function - Assessed by Questionnaire	Cochin Hand Function	Baseline to 6 weeks, 3 months and 6 months
Secondary	Fatigue - Assessed by Questionnaire	Functional Assessment of Chronic Illness Therapy (FACIT)	Baseline to 6 weeks, 3 months and 6 months
Secondary	Anxiety and depression - Assessed by questionnaire	Hospital Anxiety and Depression Scale (HADS) . This questionnaire has 14 questions, each with 4 options designed to assess aspects of mental health	Baseline to 6 weeks, 3 months and 6 months
Secondary	Health related quality of life - Assessed by Questionnaire	Helplessness Questionnaire	Baseline to 6 weeks, 3 months and 6 months
Secondary	Health related quality of life - Assessed by Questionnaire	Short Form (36) Health Survey	Baseline to 6 weeks, 3 months and 6 months
Secondary	Health related quality of Life - Assessed by Questionnaire	EuroQol 5 Dimensions	Baseline to 6 weeks, 3 months and 6 months
Secondary	Pain and disability	Patient Global Assessment	Baseline to 6 weeks, 3 months and 6 months
Secondary	Pain and disability	Physician Global Assessment	Baseline to 6 weeks, 3 months and 6 months
Secondary	Assessment of pain - Clinician assessment	Digital Ulcer Count: The site and total number of ulcers on the hand are recorded by the patients clinician on a diagram of a hand	Baseline to 6 weeks, 3 months and 6 months
Secondary	Assessment of pain - Clinician assessment	Tender Friction Rubs - the total number of tendon friction rubs on 12 possible anatomical sites are recorded	Baseline to 6 weeks, 3 months and 6 months
Secondary	Assessment of pain - Clinician assessment	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	Baseline to 6 weeks, 3 months and 6 months
Secondary	Pain and disability - Assessed by Questionnaire	Assessment of Arthritis Index	Baseline to 6 weeks, 3 months and 6 months
Secondary	Pain and disability	Assessment in percentage change of mRSS	Baseline to 6 weeks, 3 months and 6 months