Functional Exercise Tests in Patients With Systemic Sclerosis

Measurement Properties and Performance of Functional Exercise Tests in Patients With Systemic Sclerosis

The aim of the study is to examine the validity of peripheral oxygen saturation measurement during the 6-minute walk test in patients with Systemic Sclerosis (SSc) and to examine the utility of two other functional tests as markers of pulmonary involvement in patients with SSc.

Study Overview

• Status: Active, not recruiting
• Conditions: Scleroderma, Systemic; Pulmonary Arterial Hypertension; Lung Diseases, Interstitial; Acroosteolysis
• Intervention / Treatment: Diagnostic test: 6-minute walk test part one; Diagnostic test: 1-minute sit-to-stand test; Diagnostic test: 4-meters gait speed test; Diagnostic test: Nailfold videocapillaroscopy; Diagnostic test: HR-pQCT; Diagnostic test: Hand x-ray; Diagnostic test: DEXA; Diagnostic test: 6-minute walk test part two

Detailed Description

Systemic Sclerosis (SSc) is a connective tissue disease characterized by progressive organ fibrosis and vascular dysfunction. The leading causes of disease related morbidity and mortality are interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). The 6-minute walk test (6MWT) is a submaximal functional exercise test used to evaluate ILD and PAH in patients with SSc. Desaturations during the 6MWT have been considered suggestive of ILD and PAH. Still, the optimal method to measure peripheral oxygen saturation during the 6MWT in patients with SSc remains unclear. Furthermore, other functional exercise tests may also be useful in patients with SSc.

Patients with SSc will perform three functional exercise tests, and approximately half of the patients will be invited to repeat the tests 1 week later to determine test-retest reliability. Additionally, nailfold videocapillaroscopy (NVC) will be performed on every patient to assess the capillary density of the nailfold of the fingers. Furthermore, to study the effect of SSc on bone, a high resolution peripheral quantitative computed tomography (HRpQCT) scan of radius and distal interphalangeal joints (DIP)/distal phalanges will be performed.

During the 6MWT, the peripheral oxygen saturation (SpO2) will be measured continuously on three anatomical locations. An arterial line will be placed, and blood will be drawn at baseline and after ended 6MWT and analysed for arterial oxygen saturation (SaO2). The correlation between the capillary density of the nailfold and the SpO2 measured on the finger will be assessed. The correlation between capillary density of the nailfold and bone status in the fingers and distal radius assessed with HRpQCT will be evaluated, and HRpQCT images will be compared with conventional radiography and DEXA. Bland-Altman plot will be used to display the agreement between SaO2 and SpO2 and between the two 6MWT. Further, the association between pulmonary variables and 6MWT results will be examined.

Two alternative functional exercise tests will be investigated and compared to results in the 6MWT: The 1-minute sit-to-stand test (1STST) and the 4-meter gait speed test (4MGS). The association between the three functional exercise tests and clinical parameters in patients with SSc will be examined.

• Study Type: Observational
• Enrollment (Anticipated): 83

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • The Department of Rheumatology, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients are recruited if they have a clinical course at the Department of Rheumatology, Aarhus University Hospital (>500 patients with Scleroderma)

Description

Inclusion Criteria:

• Diagnosed with Systemic Sclerosis according to the ACR/EULAR 2013 criteria
• Provided written informed consent

Exclusion Criteria:

• Overlap syndrome (except for rheumatoid arthritis and Sjögren syndrome)
• Recent or ongoing lung infection
• Other major comorbidities that could affect the functional exercise tests.
• Pregnancy
• Unable to understand the patient information

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Part one of the project; 83 patients with Systemic Sclerosis will perform three functional exercise tests on the same day. All 83 patients will be examined with NVC. Moreover, HRpQCT will be performed on all patients at baseline and after 1 year.	Diagnostic test: 6-minute walk test part one; Measurement of: 6-minute walk distance, the modified Borg scale before and after testing and continuous measure of peripheral oxygen saturation and heart rate. The peripheral oxygen saturation will be measured continuously on three anatomical location: the forehead, an earlobe and a finger. In patients who will accept an arterial line will be placed and blood gas will be analyzed.; Diagnostic test: 1-minute sit-to-stand test; Measurement of: Number of repetitions, the modified Borg scale before and after testing and continuous measure of peripheral oxygen saturation and heart rate. The peripheral oxygen saturation will be measured on the three anatomical locations mentioned above.; Diagnostic test: 4-meters gait speed test; Measurement of: Time to complete the 4 meters course and calculation of the 4-meters-gait-speed.; Diagnostic test: Nailfold videocapillaroscopy; Capillary density measurement of: The finger with the probe and the average of all the fingers. NVC with 200 x magnification will be performed on the 2nd to 5th finger on both hands.; Diagnostic test: HR-pQCT; Imaging: One arm is scanned in a 9 mm-long volume of the distal radius (110 slices), and the distal part of the 2nd to 5th finger on both hands are scanned in a 36,08 mm-long volume (440 slices) at baseline and after 1 year.; Diagnostic test: Hand x-ray; Imaging: Hand x-ray was performed on patients scanned with HR-pQCT, unless images were already available (≤ 1 year).; Diagnostic test: DEXA; Imaging: A bone density (DEXA) scan was performed on patients scanned with HR-pQCT, unless it was already available (≤ 2 years).
Part two of the project; Half of the patients from part one of the project will be invited to repeat the three functional exercise tests approximately one week later in reverse order to determine test-retest reliability.	Diagnostic test: 1-minute sit-to-stand test; Measurement of: Number of repetitions, the modified Borg scale before and after testing and continuous measure of peripheral oxygen saturation and heart rate. The peripheral oxygen saturation will be measured on the three anatomical locations mentioned above.; Diagnostic test: 4-meters gait speed test; Measurement of: Time to complete the 4 meters course and calculation of the 4-meters-gait-speed.; Diagnostic test: 6-minute walk test part two; Measurement of: 6-minute walk distance, the modified Borg scale before and after testing and continuous measure of peripheral oxygen saturation and heart rate. The peripheral oxygen saturation will be measured continuously on three anatomical location: the forehead, an earlobe and a finger. No arterial line will be placed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Examine the validity of peripheral oxygen saturation measurement during 6-minute walk test in patients with Systemic Sclerosis.	The agreement between the peripheral oxygen saturation measured on the forehead, finger and earlobe and the arterial oxygen saturation from the blood gas analysis will be examined.	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Examine the correlation between the 6-minute walk test, the 1-minute sit-to-stand test, and the 4-meter gait speed test in patients with Systemic Sclerosis.	The agreement between the 6-minute walk test, the 1-minute sit-to-stand test, and the 4-meter gait speed test in patients with Systemic Sclerosis.	1 hour
Investigate the correlation between functional exercise tests and the severity of pulmonary involvement in patients with Systemic Sclerosis.	The agreement between functional exercise tests and the severity of pulmonary involvement in patients with Systemic Sclerosis.	1 hour

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: The Danish Rheumatism Association
• Investigators: Study Chair: Klaus Søndergaard, MD, PhD, Department of Rheumatology, Aarhus University Hospital, DK; Principal Investigator: Amanda Lynggaard Riis, Student, Department of Rheumatology, Aarhus University Hospital, DK; Study Director: Esben Uggerby Næser, MD, PhD, Department of Rheumatology, Aarhus University Hospital, DK; Principal Investigator: Katja Thorup Aaen, Student, Department of Rheumatology, Aarhus University Hospital, DK; Study Chair: Ellen-Margrethe Hauge, Professor, Department of Rheumatology, Aarhus University Hospital, DK; Principal Investigator: Frederik Cosedis Enevoldsen, Student, Department of Rheumatology, Aarhus University Hospital, DK; Study Director: Rasmus Klose Jensen, MD, PhD, Department of Rheumatology, Aarhus University Hospital, DK; Study Director: Josephine Therkildsen, MD, Department of Rheumatology, Aarhus University Hospital, DK

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2021
• Primary Completion (Anticipated): January 31, 2023
• Study Completion (Anticipated): January 31, 2023

Study Registration Dates

• First Submitted: November 23, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): May 20, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Oximetry; HR-pQCT; Exercise test; Scleroderma, Systemic; 6-Minute Walk Test; Raynaud Disease; Nailfold videocapillaroscopy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Respiratory Tract Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Hypertension, Pulmonary; Bone Diseases, Developmental; Bone Resorption; Osteolysis; Hypertension; Lung Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Pulmonary Arterial Hypertension; Lung Diseases, Interstitial; Acro-Osteolysis
• Other Study ID Numbers: SSc6MWT2020; 1-16-02-270-20 (Other Identifier: The Danish Data Protection Agency)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No