Systemic SclerosisNCT03058887
The Effects of Exercise in Patients With Systemic Sclerosis
A study testing Exercise intervention - Cycling and Exercise intervention - arm cranking in people with Systemic Sclerosis and Raynaud's Phenomenon, run by Sheffield Hallam University at 2 sites in United Kingdom.
Trial summary
Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised by vascular abnormalities and fibrosis, including those of the skin and can be categorised as either Limited cutaneous scleroderma or Diffuse cutaneous scleroderma. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Systemic Sclerosis, Raynaud's Phenomenon, Quality of Life
- What is being tested?
- Exercise intervention - Cycling and Exercise intervention - arm cranking
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Jun 2016to Sep 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients diagnosed with Limited Cutaneous Systemic Sclerosis according to the 2013 ACR/EULAR criteria experiencing Raynaud's phenomenon.
- Men or women aged 18-80 years old.
- Disease duration between 1 to 10 years.
- Patients should be able to perform exercise. Exclusion criteria
- Patients with advanced pulmonary arterial hypertension or interstitial lung disease.
- Patients who are diagnosed with another inflammatory condition.
Show all 10Show fewer
- Patients presenting myositis with proximal muscle weakness.
- Patients with New York Heart Association class 3 or 4.
- Current smokers or people who stopped smoking within 4 weeks of health screening.
- Women who are currently pregnant.
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Sheffield Hallam University
Sheffield, S10 2BP
Royal Hallamshire Hospital
Sheffield, S10 2JF
About this study
Official title: Investigating the Effectiveness and Feasibility of Exercise on Microcirculatory Parameters and Quality of Life in Systemic Sclerosis Patients Experiencing Raynaud's Phenomenon.
Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised by vascular abnormalities and fibrosis, including those of the skin and can be categorised as either Limited cutaneous scleroderma or Diffuse cutaneous scleroderma. It is estimated that more than 90% of patients with SSc experience Raynaud's phenomenon (RP) at regular intervals during the course of their disease. Approximately 50% of patients with SSc develop severe digital ischaemia and/or ulceration which seems to be painful, difficult to heal, susceptible to infections and heavily influences quality of life and increases SSc-related disability.
Medical treatment is commonly used as an effective first line approach in the NHS policy when uncontrolled RP attacks emerge. However, considering the short-term side effects (oedema, headaches, heart palpitations, dizziness and constipation) but also the long-term side effects of nifedipine (heart dysfunction and increased cardiovascular risk) as well as the financial cost of this approach, alternative approaches with less side effects and less cost implications are warranted.
Read more
An alternative approach would be to implement a programme of therapeutic exercise that would be suitable for this patient group. To the investigators knowledge the efficacy of exercise on microcirculation in RP has not been previously examined. In this regard, high intensity interval training (HIIT) has come to prominence over the last years for its effectiveness in inducing greater improvements in vascular function than moderate intensity continuous training. Due to the variation in HIIT protocols evidence is limited to support which protocol is the most effective in SSc patients. Moreover, it should be noted that the chief aim of the research project is to encourage long-term adherence to physical activity and rehabilitation programmes in these patients which might be beneficial for the vascular function. A short HIIT protocol (30seconds/passive recovery) may elicit more favourable patient reported satisfaction /enjoyment levels compared to other longer exercise duration protocols. A short HIIT protocol (30seconds/passive recovery) has demonstrated to be well tolerated, preferred protocol with a low perception of effort, patient comfort and with a longer time spent at high percentage of V̇O2peak than a longer HIIT protocol with active recovery phases in chronic heart failure patients. More recent evidence supports this notion; when enjoyment levels in an overweight/obese cohort were examined after a short HIIT protocol.
Although it is known that HIIT is capable to improve vascular function and potentially the microcirculatory parameters, evidence is scarce regarding the mode of exercise that will be more effective on digital microcirculation where the RP attacks are present in SSc patients. Assumptions could be made that utilising an upper-body exercise would potentially be more beneficial for the digital microcirculation rather than lower-body exercise where the working muscles promote the blood flow in the lower limbs. Hence, the differential effects that may occur by the upper- and lower-limb exercise on the digital microcirculation in SSc patients should be examined.
Resistance training (RT) alone has shown significant improvements in the function of the vasculature; moreover, a combination of aerobic and RT have shown both in the past and recently important enhances in the vascular function and microcirculation. However, the limited number of studies have investigated the effects of RT on vasculature bespeaks a lack of concrete evidence. Moreover, to the investigators knowledge the effects of combined exercise (RT and aerobic exercise) utilising a HIIT protocol and RT on microcirculation has yet to be examined.
Aims:
The primary aim of the present study is to examine the feasibility of exercise in patients with Systemic Sclerosis experiencing Raynaud's Phenomenon.
- Conditions
- Systemic Sclerosis, Raynaud's Phenomenon, Quality of Life
- Being tested
- Exercise intervention - Cycling, Exercise intervention - arm cranking
- Keywords
- High Intensity Interval Training, Exercise, Microcirculation
- Medical subject headings
- Scleroderma, Systemic, Raynaud Disease, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise intervention - CyclingOther
The patients that will be randomly allocated to the exercise group - cycling will be requested to perform an exercise session on a cycle ergometer. Each training will be consisted of high intensity interval training for 30 minutes (30s 100% PPO/ 30s passive recovery) twice per week for 3 months. Patients will perform two visits for the baseline measurements prior the exercise intervention by repeating them at the end of the exercise intervention (follow up measurements).
Exercise intervention - arm crankingOther
The patients that will be randomly allocated to the exercise group - arm cranking will be requested to perform an exercise session on an arm crank ergometer. Each training will be consisted of high intensity interval training for 30 minutes (30s 100% PPO/ 30s passive recovery) twice per week for 3 months. Patients will perform two visits for the baseline measurements prior the exercise intervention by repeating them at the end of the exercise intervention (follow up measurements).
| Study group | Role | What they receive |
|---|---|---|
| Arm cranking | Experimental | exercising for 3 months twice per week. Receives: Other: Exercise intervention - arm cranking |
| Cycling | Experimental | exercising for 3 months twice per week. Receives: Other: Exercise intervention - Cycling |
| Control group | No intervention | No exercise intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part I (Pilot study): Microcirculation in the digital area
Microcirculation will be assessed via the combination of iontophoresis and laser doppler fluximetry in order to assess the microvascular reactivity pre and post the exercise intervention in the digital area.
Measured: 12 months
Part II (Feasibility study): Feasibility of a combined exercise protocol (aerobic with resistance training).
The feasibility of the exercise protocol will be assessed via the acceptability of the exercise protocol which will be measured with certain questionnaires (task self efficacy, enjoyment levels and engagement levels), individual experiences from the exercise sessions (interviews) and compliance criteria (e.g. completion of > 75% of the scheduled sessions and/or percentage of dropouts).
All these measures will be aggregated in order to conclude whether a combined exercise is feasible to be implemented in patients with systemic sclerosis.
Measured: 12 months
Part II (Feasibility study): Assessment of Quality of life
The quality of life will be assessed through a modified version of EQ-5D-5L questionnaire, a 6 minute-walking test that will assess the functional capacity to perform daily activities and individual experiences (interviews).
Measured: 12 months
Secondary outcomes (3)
Part I (Pilot study): Quality of life
The quality of life will be assessed through a modified version of EQ-5D-5L questionnaire, a 6 minute-walking test that will assess the functional capacity to perform daily activities and individual experiences (interviews).
Measured: 12 months
Part I (Pilot study): Enjoyment levels and acceptability of exercise
The acceptability of the exercise protocol and enjoyment levels which will be assessed via certain questionnaires (task self efficacy, enjoyment levels and engagement levels)
Measured: 12 months
Part II (Feasibility): Microcirculation in the digital area
Microcirculation will be assessed via the combination of iontophoresis and laser doppler fluximetry in order to assess the microvascular reactivity pre and post the exercise intervention in the digital area.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2017
- Study startJun 2016
- Primary completionSep 2018
- Study completionSep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Systemic SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Hallam University
- Sponsor type
- University, hospital or other
- Collaborators
- Sheffield Teaching Hospitals NHS Foundation Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03058887
- Sponsor's protocol ID
- IRAS: 68096
- Status last verified
- Apr 2019
- First submitted
- 13 Oct 2016
- Last updated
- 8 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Mitropoulos A, Akil M, Klonizakis M. Microcirculatory responses at rest and during exercise in limited cutaneous systemic sclerosis compared to age-matched healthy adults. Front Sports Act Living. 2026 Aug 11;8:1872867. doi: 10.3389/fspor.2026.1872867. eCollection 2026.
PubMed 42643722Mitropoulos A, Gumber A, Crank H, Akil M, Klonizakis M. Exploring the feasibility of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis. Clin Rheumatol. 2020 Jun;39(6):1889-1898. doi: 10.1007/s10067-019-04921-7. Epub 2020 Jan 14.
PubMed 31933034Mitropoulos A, Gumber A, Akil M, Klonizakis M. Exploring the microcirculatory effects of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis. Microvasc Res. 2019 Sep;125:103887. doi: 10.1016/j.mvr.2019.103887. Epub 2019 Jun 17.
PubMed 31220505Mitropoulos A, Gumber A, Crank H, Akil M, Klonizakis M. Investigating the effectiveness and feasibility of exercise on microvascular reactivity and quality of life in systemic sclerosis patients: study protocol for a feasibility study. Trials. 2018 Nov 21;19(1):647. doi: 10.1186/s13063-018-2980-1.
PubMed 30463598Mitropoulos A, Gumber A, Crank H, Akil M, Klonizakis M. The effects of upper and lower limb exercise on the microvascular reactivity in limited cutaneous systemic sclerosis patients. Arthritis Res Ther. 2018 Jun 5;20(1):112. doi: 10.1186/s13075-018-1605-0.
PubMed 29871697
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Effectiveness and Feasibility of Exercise on Microcirculatory Parameters and Quality of Life in Systemic Sclerosis Patients Experiencing Raynaud's Phenomenon.
- ClinicalTrials.gov ID
- NCT03058887
- Acronym / sponsor ID
- IRAS: 68096
- Conditions
- Systemic Sclerosis, Raynaud's Phenomenon, Quality of Life
- Keywords
- High Intensity Interval Training, Exercise, Microcirculation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Sheffield Hallam UniversityUniversity, hospital or other
- Collaborators
- Sheffield Teaching Hospitals NHS Foundation Trust
- Study start
- Jun 2016
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 23 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised by vascular abnormalities and fibrosis, including those of the skin and can be categorised as either Limited cutaneous scleroderma or Diffuse cutaneous scleroderma. It is estimated that more than 90% of patients with SSc experience Raynaud's phenomenon (RP) at regular intervals during the course of their disease. Approximately 50% of patients with SSc develop severe digital ischaemia and/or ulceration which seems to be painful, difficult to heal, susceptible to infections and heavily influences quality of life and increases SSc-related disability.
Medical treatment is commonly used as an effective first line approach in the NHS policy when uncontrolled RP attacks emerge. However, considering the short-term side effects (oedema, headaches, heart palpitations, dizziness and constipation) but also the long-term side effects of nifedipine (heart dysfunction and increased cardiovascular risk) as well as the financial cost of this approach, alternative approaches with less side effects and less cost implications are warranted.
An alternative approach would be to implement a programme of therapeutic exercise that would be suitable for this patient group. To the investigators knowledge the efficacy of exercise on microcirculation in RP has not been previously examined. In this regard, high intensity interval training (HIIT) has come to prominence over the last years for its effectiveness in inducing greater improvements in vascular function than moderate intensity continuous training. Due to the variation in HIIT protocols evidence is limited to support which protocol is the most effective in SSc patients. Moreover, it should be noted that the chief aim of the research project is to encourage long-term adherence to physical activity and rehabilitation programmes in these patients which might be beneficial for the vascular function. A short HIIT protocol (30seconds/passive recovery) may elicit more favourable patient reported satisfaction /enjoyment levels compared to other longer exercise duration protocols. A short HIIT protocol (30seconds/passive recovery) has demonstrated to be well tolerated, preferred protocol with a low perception of effort, patient comfort and with a longer time spent at high percentage of V̇O2peak than a longer HIIT protocol with active recovery phases in chronic heart failure patients. More recent evidence supports this notion; when enjoyment levels in an overweight/obese cohort were examined after a short HIIT protocol.
Although it is known that HIIT is capable to improve vascular function and potentially the microcirculatory parameters, evidence is scarce regarding the mode of exercise that will be more effective on digital microcirculation where the RP attacks are present in SSc patients. Assumptions could be made that utilising an upper-body exercise would potentially be more beneficial for the digital microcirculation rather than lower-body exercise where the working muscles promote the blood flow in the lower limbs. Hence, the differential effects that may occur by the upper- and lower-limb exercise on the digital microcirculation in SSc patients should be examined.
Resistance training (RT) alone has shown significant improvements in the function of the vasculature; moreover, a combination of aerobic and RT have shown both in the past and recently important enhances in the vascular function and microcirculation. However, the limited number of studies have investigated the effects of RT on vasculature bespeaks a lack of concrete evidence. Moreover, to the investigators knowledge the effects of combined exercise (RT and aerobic exercise) utilising a HIIT protocol and RT on microcirculation has yet to be examined.
Aims:
The primary aim of the present study is to examine the feasibility of exercise in patients with Systemic Sclerosis experiencing Raynaud's Phenomenon.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm cranking | Experimental | Other: Exercise intervention - arm crankingexercising for 3 months twice per week. |
| Cycling | Experimental | Other: Exercise intervention - Cyclingexercising for 3 months twice per week. |
| Control group | No intervention | –No exercise intervention. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients diagnosed with Limited Cutaneous Systemic Sclerosis according to the 2013 ACR/EULAR criteria experiencing Raynaud's phenomenon.
- Men or women aged 18-80 years old.
- Disease duration between 1 to 10 years.
- Patients should be able to perform exercise. Exclusion criteria
- Patients with advanced pulmonary arterial hypertension or interstitial lung disease.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise intervention - CyclingThe patients that will be randomly allocated to the exercise group - cycling will be requested to perform an exercise session on a cycle ergometer. Each training will be consisted of high intensity interval training for 30 minutes (30s 100% PPO/ 30s passive recovery) twice per week for 3 months. Patients will perform two visits for the baseline measurements prior the exercise intervention by repeating them at the end of the exercise intervention (follow up measurements). | Other | Cycling |
| Exercise intervention - arm crankingThe patients that will be randomly allocated to the exercise group - arm cranking will be requested to perform an exercise session on an arm crank ergometer. Each training will be consisted of high intensity interval training for 30 minutes (30s 100% PPO/ 30s passive recovery) twice per week for 3 months. Patients will perform two visits for the baseline measurements prior the exercise intervention by repeating them at the end of the exercise intervention (follow up measurements). | Other | Arm cranking |
Primary outcome
Part I (Pilot study): Microcirculation in the digital area
Time frame: 12 months
Microcirculation will be assessed via the combination of iontophoresis and laser doppler fluximetry in order to assess the microvascular reactivity pre and post the exercise intervention in the digital area.
Part II (Feasibility study): Feasibility of a combined exercise protocol (aerobic with resistance training).
Time frame: 12 months
The feasibility of the exercise protocol will be assessed via the acceptability of the exercise protocol which will be measured with certain questionnaires (task self efficacy, enjoyment levels and engagement levels), individual experiences from the exercise sessions (interviews) and compliance criteria (e.g. completion of > 75% of the scheduled sessions and/or percentage of dropouts). All these measures will be aggregated in order to conclude whether a combined exercise is feasible to be implemented in patients with systemic sclerosis.
Part II (Feasibility study): Assessment of Quality of life
Time frame: 12 months
The quality of life will be assessed through a modified version of EQ-5D-5L questionnaire, a 6 minute-walking test that will assess the functional capacity to perform daily activities and individual experiences (interviews).
3 secondary outcomes
Part I (Pilot study): Quality of life
Time frame: 12 months
Part I (Pilot study): Enjoyment levels and acceptability of exercise
Time frame: 12 months
Part II (Feasibility): Microcirculation in the digital area
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2019.
- Derived from this study: PubMed 42643722Mitropoulos A, Akil M, Klonizakis M. Microcirculatory responses at rest and during exercise in limited cutaneous systemic sclerosis compared to age-matched healthy adults. Front Sports Act Living. 2026 Aug 11;8:1872867. doi: 10.3389/fspor.2026.1872867. eCollection 2026.
- Derived from this study: PubMed 31933034Mitropoulos A, Gumber A, Crank H, Akil M, Klonizakis M. Exploring the feasibility of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis. Clin Rheumatol. 2020 Jun;39(6):1889-1898. doi: 10.1007/s10067-019-04921-7. Epub 2020 Jan 14.
- Derived from this study: PubMed 31220505Mitropoulos A, Gumber A, Akil M, Klonizakis M. Exploring the microcirculatory effects of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis. Microvasc Res. 2019 Sep;125:103887. doi: 10.1016/j.mvr.2019.103887. Epub 2019 Jun 17.
- Derived from this study: PubMed 30463598Mitropoulos A, Gumber A, Crank H, Akil M, Klonizakis M. Investigating the effectiveness and feasibility of exercise on microvascular reactivity and quality of life in systemic sclerosis patients: study protocol for a feasibility study. Trials. 2018 Nov 21;19(1):647. doi: 10.1186/s13063-018-2980-1.
- Derived from this study: PubMed 29871697Mitropoulos A, Gumber A, Crank H, Akil M, Klonizakis M. The effects of upper and lower limb exercise on the microvascular reactivity in limited cutaneous systemic sclerosis patients. Arthritis Res Ther. 2018 Jun 5;20(1):112. doi: 10.1186/s13075-018-1605-0.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise intervention - Cycling and Exercise intervention - arm cranking in people with Systemic Sclerosis and Raynaud's Phenomenon, run by Sheffield Hallam University at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part I (Pilot study): Microcirculation in the digital area (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03058887, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2019.