Prednisolone in Early Diffuse Systemic Sclerosis (PRedSS)

July 29, 2021 updated by: Prof. Ariane herrick

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
35

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Bristol, United Kingdom, BS10 5NB
        • Southmead Hospital Bristol - North Bristol NHS Trust
      • Dundee, United Kingdom, DD1 9SY
        • Ninewells Hospital and Medical School - NHS Tayside
      • London, United Kingdom, NW3 2QG
        • Royal Free London NHS Foundation Trust
    • Aberdeenshire
      • Aberdeen, Aberdeenshire, United Kingdom, AB25 2ZN
        • Aberdeen Royal Infirmary - NHS Grampian
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
        • Addenbrooke'S Hospital - Cambridge University Hospitals Nhs Foundation Trust
    • Greater Manchester
      • Salford, Greater Manchester, United Kingdom, M6 8HD
        • Salford Royal NHS Foundation Trust
    • Lanarkshire
      • Glasgow, Lanarkshire, United Kingdom, G4 0SF
        • Glasgow Royal Infirmary -
    • Merseyside
      • Liverpool, Merseyside, United Kingdom, L9 7AL
        • Aintree University Hospitals NHS Foundation Trust
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
        • Queen's Medical Centre - Nottingham University Hospitals NHS Trust
    • Somerset
      • Bath, Somerset, United Kingdom, BA1 1RL
        • Royal National Hospital for Rheumatic Diseases - Royal United Hospitals Bath NHS Foundation Trust
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2JF
        • Royal Hallamshire Hospital - SHEFFIELD TEACHING HOSPITALS NHS FOUNDATION TRUST
    • Tyne And Wear
      • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN
        • Freeman Hospital - THE NEWCASTLE UPON TYNE HOSPITALS NHS FOUNDATION TRUST
    • West Midlands
      • Dudley, West Midlands, United Kingdom, DY1 2HQ
        • The Dudley Group NHS Foundation Trust
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS7 4SA
        • Leeds Institute of Rheumatic and Musculoskeletal Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: Prednisolone

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
5mg prednisolone, once a day for 6 months
PLACEBO_COMPARATOR: 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.
Drug: 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Health Assessment Questionnaire Disability Index (HAQ-DI)
Time Frame: Baseline to 3 months
The mean difference in HAQ-DI at 3 months
Baseline to 3 months
modified Rodnan Skin Score (mRSS)
Time Frame: Baseline to 3 months
The difference in mRSS at 3 months
Baseline to 3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Quality of life and functional ability - Assessed by Questionnaire
Time Frame: Baseline to 6 weeks and 6 months
HAQ-DI
Baseline to 6 weeks and 6 months
Pain and disability
Time Frame: Baseline to 6 weeks and 6 months
Skin involvement as measured by the mRSS
Baseline to 6 weeks and 6 months
Functional ability - Assessed by Questionnaire
Time Frame: Baseline to 6 weeks, 3 months and 6 months
11-point Scleroderma Functional Index
Baseline to 6 weeks, 3 months and 6 months
Pain associated with itch - Assessed by Questionnaire
Time Frame: Baseline to 6 weeks, 3 months and 6 months
Assessment of Pruritus
Baseline to 6 weeks, 3 months and 6 months
Hand function - Assessed by Questionnaire
Time Frame: Baseline to 6 weeks, 3 months and 6 months
Cochin Hand Function
Baseline to 6 weeks, 3 months and 6 months
Fatigue - Assessed by Questionnaire
Time Frame: Baseline to 6 weeks, 3 months and 6 months
Functional Assessment of Chronic Illness Therapy (FACIT)
Baseline to 6 weeks, 3 months and 6 months
Anxiety and depression - Assessed by questionnaire
Time Frame: 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
Baseline to 6 weeks, 3 months and 6 months
Health related quality of life - Assessed by Questionnaire
Time Frame: Baseline to 6 weeks, 3 months and 6 months
Helplessness Questionnaire
Baseline to 6 weeks, 3 months and 6 months
Health related quality of life - Assessed by Questionnaire
Time Frame: Baseline to 6 weeks, 3 months and 6 months
Short Form (36) Health Survey
Baseline to 6 weeks, 3 months and 6 months
Health related quality of Life - Assessed by Questionnaire
Time Frame: Baseline to 6 weeks, 3 months and 6 months
EuroQol 5 Dimensions
Baseline to 6 weeks, 3 months and 6 months
Pain and disability
Time Frame: Baseline to 6 weeks, 3 months and 6 months
Patient Global Assessment
Baseline to 6 weeks, 3 months and 6 months
Pain and disability
Time Frame: Baseline to 6 weeks, 3 months and 6 months
Physician Global Assessment
Baseline to 6 weeks, 3 months and 6 months
Assessment of pain - Clinician assessment
Time Frame: Baseline to 6 weeks, 3 months and 6 months
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
Assessment of pain - Clinician assessment
Time Frame: Baseline to 6 weeks, 3 months and 6 months
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
Assessment of pain - Clinician assessment
Time Frame: 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
Baseline to 6 weeks, 3 months and 6 months
Pain and disability - Assessed by Questionnaire
Time Frame: Baseline to 6 weeks, 3 months and 6 months
Assessment of Arthritis Index
Baseline to 6 weeks, 3 months and 6 months
Pain and disability
Time Frame: Baseline to 6 weeks, 3 months and 6 months
Assessment in percentage change of mRSS
Baseline to 6 weeks, 3 months and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Prof. Ariane herrick

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Versus Arthritis

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Professor Ariane Herrick, University of Manchester

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 21, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 4, 2021

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 27, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 8, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 17, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 30, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 29, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 119220

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

IPD will be shared with collaborating centres. It is undecided if this information will be shared with researchers unconnected with the trial.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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