Condition category
Musculoskeletal Diseases
Date applied
19/06/2017
Date assigned
27/06/2017
Last edited
27/06/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Systemic sclerosis (also termed 'scleroderma') is a rare, chronic disease affecting the connective tissues, blood vessels and immune system. The two most characteristic features of the disease are skin thickening and Raynaud's phenomenon (colour changes of the fingers and sometimes the toes, usually in response to cold exposure or emotional stress). However, the disease can also affect joints, tendons and internal organs, causing them to be unable to function normally. The diffuse cutaneous subtype of scleroderma, when skin thickening rapidly spreads from the hands and feet to involve the arms, legs and/or trunk, is associated with high mortality (death rates). Only around 60% of patients survive 10 years. As a result clinicians often focus on internal organ involvement. Yet on a day-to-day basis, the most distressing features of diffuse scleroderma are severe pain, itching, impaired upper and lower limb function, resulting in difficulty performing even simple tasks, and often a feeling of helplessness. These features of the disease often destroy the quality of life and, at present, there is no effective treatment. Prednisolone is a type of steroid medication that helps reduce inflammation (swelling) and could be helpful to treat this disease. The aim of this study is to see if the impact on a moderate dose of prednisolone is effective in reducing pain, disability, and skin thickening and if it is a safe therapy in patients with early diffuse scleroderma.

Who can participate?
Adults aged 18 and older who have diffuse cutaneous systemic sclerosis.

What does the study involve?
After a series of screening, eligible participants are randomly allocated to one of two groups. Those in the first group are given prednisolone taken daily by mouth for six months. Those in the second group receive a placebo (dummy) medication to take daily for six months. During this time, participants return to the clinics for monitoring at six weeks, three months and six months. Blood and urine samples are collected from participants. Participants are also given blood pressure monitors to take home and a study diary to record the readings in. After the six month visit, participants are informed of which treatment they received. Those who received the prednisolone can decide with their doctor if they would like to continue with the medication. Those who do not are advised to gradually lower their dose of the medication before stopping. Participants are recommended to see their usual doctor within 30 days of the trial. Participants are assessed for their functional abilities and pain levels to see if the medication is safe and effective.

What are the possible benefits and risks of participating?
Participants may benefit from experiencing relief in their symptoms and a reduction in pain, itching, skin function and improvements in function and quality of life. Participant’s condition may worsen but this could happen whether they participate or not. There are side effects with prednisolone, such as risk of serious kidney problems. Participants have their blood pressure monitored during the study to monitor for this. This study may disrupt participant’s normal routine as it required five extra hospital visits over six months. Participants may feel small discomfort when providing blood samples. It is very important that participants do not suddenly stop taking the study treatment. Abruptly stopping the medication will put individuals at risk of 'steroid withdrawal' symptoms and this is potentially dangerous. Suddenly stopping the study drug may require emergency medical treatment.

Where is the study run from?
This study is being run by the University of Manchester and takes place in Salford Royal NHS foundation trust (UK) and in 11 other hospitals in the UK.

When is the study starting and how long is it expected to run for?
March 2016 to March 2021

Who is funding the study?
Arthritis Research UK (UK)

Who is the main contact?
Dr Deb Griffiths-Jones
deb.griffiths-jones@manchester.ac.uk

Trial website

www.predss.org (Currently under development)

Contact information

Type

Public

Primary contact

Dr Deb Griffiths-Jones

ORCID ID

http://orcid.org/0000-0001-6606-9340

Contact details

University of Manchester
Oxford Road
Manchester
M13 9PL
United Kingdom
+44 161 275 1675
deb.griffiths-jones@manchester.ac.uk

Additional identifiers

EudraCT number

2016-002651-25

ClinicalTrials.gov number

Protocol/serial number

34302

Study information

Scientific title

A phase II randomised controlled study of oral PRednisolone in Early diffuse cutaneous Systemic Sclerosis

Acronym

PRedSS

Study hypothesis

The aim of this study is to determine whether:
1. Moderate dose prednisolone is effective in reducing pain, disability and skin thickening in patients with early diffuse scleroderma
2. Moderate dose prednisolone is a safe therapy in patients with early diffuse scleroderma (with particular reference to kidney function)

Ethics approval

North West – Great Manchester South, 26/06/2017, ref: 17/NW/0320

Study design

Randomised; Interventional; Design type: Treatment, Process of Care, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Musculoskeletal disorders, Primary sub-specialty: Other; UKCRC code/ Disease: Musculoskeletal/ Systemic connective tissue disorders

Intervention

Participants are asked to sign a consent form following a full explanation of the study. Before any treatment is given, individuals are asked to attend a screening visit. A doctor performs a physical examination and takes routine urine and blood samples. If the doctor thinks the study is suitable, participants are asked to return to the hospital a total of four more times. The next visit (baseline visit) is scheduled within 28 days of the screening visit, then again at six weeks, three months and six months. At every visit, the doctor performs a physical examination and a routine blood and urine sample are collected. At each visit, participants are also be asked to complete nine questionnaires. The questionnaires will take approximately 25 minutes to fill in.

Following screening, eligible participants are 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 participants are blind to the randomisation. A placebo control, as opposed to an active treatment control, is administered. Randomisation is conducted by the King’s CTU Randomisation service. Once site have an eligible patient, the local research team will log on to this system and participants are randomised electronically.

Patients receive either the active therapy or placebo for a total of six months, administered at the baseline visit. During the treatment period, patients will return for monitoring on 3 further occasions (six weeks, three months and six months). To avoid the risk of an Addisonian crisis, arising from the abrupt discontinuation of corticosteroid therapy, the treatment code will be broken at the six month visit. At this stage the clinician will decide, for patients receiving prednisolone, whether to recommend remaining on active treatment at the current dose, whether to reduce the dose or whether to gradually taper the dose with a view to discontinuing treatment. Blood and urine samples are also be collected to be analysed for biomarkers (substances for measuring or predicting the progress of the disease) in future scleroderma research projects. The analysis of these samples will not be part of the results of the PRedSS study. Participants are under no obligation to take part in this sample collection. Individuals are free to decide to take part in the PRedSS study but decline to have these extra samples taken. If participants provide samples for the biomarker research, no extra visits to the hospital are required. The samples are taken at baseline, three months and six months.

Participants are also be given a blood pressure monitor to take home and a study diary to record the blood pressure readings in. The doctor will advise blood pressure is measured twice a week, but this is not compulsory. Both diaries are checked at every visit by the research nurse.

At the six month visit, once all the tests have been completed, the doctor will tell participants which study treatment was received. Individuals who have been taking prednisolone will decide with the doctor if taking this medication should be continued (perhaps at a reduced dose) or gradually reduce the dose with a view to stopping the medication. At this point, individuals are no longer taking part in the PRedSS study. The doctor will recommend that participants see their usual hospital consultant within 30 days. Individuals prescribed the placebo can stop taking the capsules immediately.

Intervention type

Other

Phase

Drug names

Primary outcome measures

1. Functional ability is measured using the Health Assessment Questionnaire Disability Index (HAQ-DI) at baseline and three months
2. Pain is measured using the Health Assessment Questionnaire Disability Index (HAQ-DI) at baseline and three months
3. Skin score is measured using the modified Rodnan skin score (mRSS) at baseline and three months

Secondary outcome measures

1. Functional ability and pain are measured using the HAQ-DI at six weeks and six months
2. Skin score is measured using the mRSS at six weeks and six months
3. Percentage change in skin score from baseline is measured using the mRSS at six weeks, three months and six months
4. Functional ability, to complement the HAQ-DI, will be measured by the 11 point scleroderma functional index at baseline, six weeks, three months and six months
5. Pain is measured using the visual analogue scale (part of the HAQ-DI) at baseline, six weeks, three months and six months
6. Pruritus is measured using the 5-D Itch questionnaire at baseline, six weeks, three months and six months
7. Hand function is measured using the Cochin Hand Function scale at baseline, six weeks, three months and six months
8. Fatigue is measured using the Functional Assessment of Chronic Illness Therapy (FACIT) questionnaire at baseline, six weeks, three months and six months
9. Anxiety and depression are measured using the Hospital Anxiety and Depression Scale at baseline, six weeks, three months and six months
10. Helplessness is measured using the Helplessness questionnaire at baseline, six weeks, three months and six months
11. Health-related quality of life is measured using the Short Form (36) Health Survey (version 2) (SF-36v2) and the EuroQol five dimensions questionnaire (EQ-5D) at baseline, six weeks, three months and six months
12. A patient global assessment and physician global assessment are measured using a visual analogue scale at baseline, six weeks, three months and six months
13. Digital Ulcer Count, Tendon Friction Rubs and joint count are measured at baseline, six weeks, three months and six months
14. Arthritis Index is measured using the Rheumatology Attitudes questionnaire at baseline, six weeks, three months and six months
15. Safety measures as defined by renal crisis are measured at baseline, six weeks, three months and six month

Overall trial start date

01/04/2016

Overall trial end date

31/03/2021

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients presenting with diffuse cutaneous systemic sclerosis 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 72; UK Sample Size: 72

Participant exclusion criteria

1. Patients with significant uncontrolled Stage 1 Hypertension (clinic BP > 140/90mmHg). 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, 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. Patients with significant inflammatory bowel disease as judged by the investigator
9. It is important that patients do not suddenly stop taking the study medication

Recruitment start date

25/09/2017

Recruitment end date

24/09/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Salford Royal NHS Foundation Trust (Lead centre)
Department of Rheumatology Stott Lane
Salford
M6 8HD
United Kingdom

Trial participating centre

Royal Free Hospital
University College London Faculty of Medical Sciences Division of Medicine Centre for Rheumatology and Connective Tissue Diseases Rowland Hill Street
London
NW3 2PF
United Kingdom

Trial participating centre

Chapel Allerton Hospital
Leeds Institute of Rheumatic & Musculoskeletal Medicine (LIRMM)
Leeds
LS7 4SA
United Kingdom

Trial participating centre

Southmead Hospital
Department of Rheumatology Brunel Building
Bristol
BS10 5NB

Trial participating centre

Queen’s Medical Centre
Rheumatology Department A46 Soutch Block University Hospital NHS Trust
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Royal National Hospital for Rheumatic Diseases
Upper Borough Walls
Bath
BA1 1RL
United Kingdom

Trial participating centre

University Hospital Aintree
Institute for Ageing and Chronic Disease Faculty of Health and Life Science 3rd Floor Clinical Sciences Centre Longmoor Lane
Liverpool
L9 8ED
United Kingdom

Trial participating centre

The Freeman Hospital
Newcastle upon Tyne NHS Foundation Trust High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Trial participating centre

Old Queen Elizabeth Hospital
University Hospitals Birmingham NHS Foundation Trust Rheumatology Offices, East 1 Edgbaston
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Addenbrooke’s Hospital
Cambridge University Hospitals NHS Foundation Trust Department of Rheumatology Box 204 Hills Road
Cambridge
CB2 2QQ
United Kingdom

Trial participating centre

Glasgow Royal Infirmary
Centre for Rheumatic Diseases
Glasgow
G4 0SF
United Kingdom

Trial participating centre

Llandudno General Hospital
Peter Maddison Rheumatology Centre Conwy
Llandudno
LL30 1LB
United Kingdom

Sponsor information

Organisation

The University of Manchester

Sponsor details

Research Governance and Integrity Team
Directorate of Research and Business Engagement Support Services
Christie Building
Oxford Road
Manchester
M13 9PL
United Kingdom
+44 161 275 2725
mohammed.zubair@manchester.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Arthritis Research UK

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The main study results will be published in the name of the study in a high-impact peer-reviewed journal, on behalf of all collaborators.

IPD sharing statement:
The current data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

31/03/2022

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes