The Effects of Exercise in Patients With Systemic Sclerosis

• ClinicalTrials.gov Identifier: NCT03058887
• Recruitment Status: Completed
• First Posted: February 23, 2017
• Last Update Posted: April 8, 2019
• Sponsor: Sheffield Hallam University
• Collaborator: Sheffield Teaching Hospitals NHS Foundation Trust
• Information provided by (Responsible Party): Sheffield Hallam University

Tracking Information

• First Submitted Date: October 13, 2016
• First Posted Date: February 23, 2017
• Last Update Posted Date: April 8, 2019
• Study Start Date: June 2016
• Actual Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 15, 2017)

• 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).

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03058887 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: February 15, 2017)

• Part I (Pilot study): 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).
• Part I (Pilot study): Enjoyment levels and acceptability of exercise [ Time Frame: 12 months ]
  The acceptability of the exercise protocol and enjoyment levels which will be assessed via certain questionnaires (task self efficacy, enjoyment levels and engagement levels)
• Part II (Feasibility): 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Effects of Exercise in Patients With Systemic Sclerosis
• Official Title: Investigating the Effectiveness and Feasibility of Exercise on Microcirculatory Parameters and Quality of Life in Systemic Sclerosis Patients Experiencing Raynaud's Phenomenon.

Brief 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. 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other

Condition

• Systemic Sclerosis
• Raynaud's Phenomenon
• Quality of Life

Intervention

• Other: Exercise intervention - Cycling
  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).
• Other: Exercise intervention - arm cranking
  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 Arms

• Experimental: Arm cranking
  exercising for 3 months twice per week.
  Intervention: Other: Exercise intervention - arm cranking
• Experimental: Cycling
  exercising for 3 months twice per week.
  Intervention: Other: Exercise intervention - Cycling
• No Intervention: Control group
  No exercise intervention.

Publications *

• Mitropoulos 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.
• Mitropoulos 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.
• Mitropoulos 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 15, 2017): 36
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: September 2018
• Actual Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria

• 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.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03058887
• Other Study ID Numbers: IRAS: 68096
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Sheffield Hallam University
• Study Sponsor: Sheffield Hallam University
• Collaborators: Sheffield Teaching Hospitals NHS Foundation Trust
• Investigators: Not Provided
• PRS Account: Sheffield Hallam University
• Verification Date: April 2019