Prednisolone in Early Diffuse Systemic Sclerosis

NCT03708718 | Completed Phase 2 DMC

• 1 other identifier: 119220
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 14

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.

Conditions

Systemic Sclerosis

Keywords

Diffuse cutaneous systemic sclerosis (dcSSc); Prednisolone; Randomised Controlled Trial; Disability; Pain; Fatigue

Outcome Measures

Primary Outcomes (2)

• Health Assessment Questionnaire Disability Index (HAQ-DI)

  The mean difference in HAQ-DI at 3 months

  Baseline to 3 months

• modified Rodnan Skin Score (mRSS)

  The difference in mRSS at 3 months

  Baseline to 3 months

Secondary Outcomes (17)

• Quality of life and functional ability - Assessed by Questionnaire

  Baseline to 6 weeks and 6 months

• Pain and disability

  Baseline to 6 weeks and 6 months

• Functional ability - Assessed by Questionnaire

  Baseline to 6 weeks, 3 months and 6 months

• Pain associated with itch - Assessed by Questionnaire

  Baseline to 6 weeks, 3 months and 6 months

• Hand function - Assessed by Questionnaire

  Baseline to 6 weeks, 3 months and 6 months

Study Arms (2)

Prednisolone

ACTIVE COMPARATOR

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.

Drug: Prednisolone 5 mg

Placebo oral capsule; From August 2020 - 'no additional treatment'

PLACEBO COMPARATOR

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.

Drug: Placebo oral capsule; From August 2020 'no additional treatment'

Interventions

Prednisolone 5 mg DRUG

5mg prednisolone, once a day for 6 months

Prednisolone

Placebo oral capsule; From August 2020 'no additional treatment' DRUG

Matched placebo capsule, once a day for 6 months; From August 2020 - no additional treatment above standard of care medication

Placebo oral capsule; From August 2020 - 'no additional treatment'

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Prof. Ariane herrick: lead
• Versus Arthritis: collaborator

Study Sites (14)

Aberdeen Royal Infirmary - NHS Grampian

Aberdeen, Aberdeenshire, AB25 2ZN, United Kingdom

Location

Addenbrooke's Hospital - Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, Greater Manchester, M6 8HD, United Kingdom

Location

Glasgow Royal Infirmary -

Glasgow, Lanarkshire, G4 0SF, United Kingdom

Location

Aintree University Hospitals NHS Foundation Trust

Liverpool, Merseyside, L9 7AL, United Kingdom

Location

Queen's Medical Centre - Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

Royal National Hospital For Rheumatic Diseases - Royal United Hospitals Bath NHS Foundation Trust

Bath, Somerset, BA1 1RL, United Kingdom

Location

Royal Hallamshire Hospital - Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, South Yorkshire, S10 2JF, United Kingdom

Location

Freeman Hospital - The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

Location

The Dudley Group NHS Foundation Trust

Dudley, West Midlands, DY1 2HQ, United Kingdom

Location

Leeds Institute of Rheumatic and Musculoskeletal Medicine

Leeds, West Yorkshire, LS7 4SA, United Kingdom

Location

Southmead Hospital Bristol - North Bristol NHS Trust

Bristol, BS10 5NB, United Kingdom

Location

Ninewells Hospital and Medical School - NHS Tayside

Dundee, DD1 9SY, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Related Publications (1)

• Griffiths-Jones DJ, Garcia YS, Ryder WD, Pauling JD, Hall F, Lanyon P, Bhat S, Douglas K, Gunawardena H, Akil M, Anderson M, Griffiths B, Del Galdo F, Youssef H, Madhok R, Arthurs B, Buch M, Fligelstone K, Zubair M, Mason JC, Denton CP, Herrick AL. A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS). Rheumatology (Oxford). 2023 Sep 1;62(9):3133-3138. doi: 10.1093/rheumatology/kead012.

  PMID: 36637209 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic; Scleroderma, Diffuse; Pain; Fatigue

Interventions

Prednisolone

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Professor Ariane Herrick

  University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind. The trial management team are blind to treatment allocation for the duration of the trial. The site research teams and patients are blind to treatment until code-break. At this point the on-site team and patient are unblind to allocation for continuing care. The site pharmacy personnel, PRedSS trial monitor and supervising statistician are unblind throughout. From August 2020: Open-Label - The patient, site research team and site pharmacy are unblind. The trial management team are unblind for patients recruited from August 2020 onwards but remain blind to patients randomised to trial under the double-blind design. The trial monitor and trial statistician continue to be unblind for all patients randomised to trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Rheumatology

Model Details: Patients are allocated to received either prednisolone or matched placebo for the duration of the trial. The allocation is randomised 1:1. From August 2020: Under the open-label design, patients are allocated to receive prednisolone or no additional treatment. The randomisation allocation is 1:1.

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 17, 2018
• Study Start: December 21, 2017
• Primary Completion: March 4, 2021
• Study Completion: May 27, 2021
• Last Updated: July 30, 2021

Record last verified: 2021-07

Locations

GB (14)