Systemic Lupus ErythematosusNCT03186794
Aerobic Exercise in Women With Systemic Lupus Erythematosus
A study testing Treadmill exercise training in people with Systemic Lupus Erythematosus and Lupus, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial summary
Background: As many as 1.5 million Americans are living with systemic lupus erythematosus (Lupus). Lupus makes people very tired. It also makes it hard for people to be physically active. Studies have shown that aerobic exercise training helps people with heart or lung illnesses be less tired and more active. Read more about this study
- Who is it for?
- Ages 21 to 80 years, women only
- Conditions the study is for
- Systemic Lupus Erythematosus, Lupus, Autoimmune Disease
- What is being tested?
- Treadmill exercise training
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Feb 2018to 25 Feb 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Fulfilling 4 of the 11 American College of Rheumatology Criteria for the Classification of Systemic Lupus Erythematosus
- Age 21 to 80
- Female Gender
- BMI less than 40
- No primary or secondary medical conditions that would limit aerobic capacity or make exercise participation unsafe. (These conditions are found under the exclusion criteria listed below and include cardiovascular disease and cardiomyopathy, pulmonary and pulmonary vascular disease, stroke, significant hepatic or renal dysfunction, most cancers, diabetes mellitus, HIV infection, and peripheral vascular disease.)
- SELENA-SLEDAI score less than or equal to 4, maintained for at least three months. (C3 and C4 levels are measured as markers for stability and included in the SELENA-SLEDAI score if abnormal).
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- No increase in doses of immunosuppressive medications (hydroxychloroquine, mycophenolate mofetil, azathioprine, methotrexate) for at least three months at the time of screening.
- No increase in the dose of prednisone or equivalent steroid in the past 3 months at the time of screening.
- Physically inactive, not participating in aerobic exercise training at heart rate above 60% maximum heart rate, 20 min/session or more, 2 or more days per week, within the last 6 months at the time of screening.
- Fatigue Severity Scale (FSS) composite score greater than or equal to 3 indicating the presence of clinically significant fatigue
- Subjects must be able to walk on a treadmill
Who cannot join
- Prednisone greater than or equal to 15 mg daily (or equivalent)
- Have started azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide or biologics within 3 months
- Rituximab infusion within 6 months
- Present symptoms of ischemic heart disease, right- or left-sided heart failure, cor pulmonale or pulmonary hypertension, dilated or hypertrophic cardiomyopathy or non- idiopathic cardiomyopathy
- Significant pulmonary dysfunction (obstructive, restrictive, or infectious pulmonary disease)
- Significant hepatic (LFT > 2 times of upper limit of normal) or renal dysfunction (GFR<45 ml/min)
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- Deep vein thrombosis
- Chronic anticoagulation (with the exception of low dose aspirin) or a history of a bleeding disorder
- History or presence of any form of cancer other than skin cancer or cervical in-situ cancer
- History of cerebrovascular accident
- Orthopedic conditions that would limit performance of treadmill exercise tests or treadmill exercise training
- Current smoker or active substance abuse
- HIV infection
- Any medication that limit exercise capacity or the ability to adapt to aerobic exercise training (e.g. beta-blockers, anti-retroviral therapy for the treatment of HIV infection)
- Diabetes Mellitus
- Fibromyalgia: Determined at pre-screening visit, as per 2010 American College of Rheumatology (ACR) criteria for diagnosis of fibromyalgia
- Uncontrolled or untreated thyroid dysfunction: Determined by abnormal Thyroid Stimulating Hormone (TSH) level checked at the time of screening or within 3 months before screening visit.
- Currently pregnant, nursing or plan to become pregnant during the duration of the study
- Anemia (hemoglobin < 9 g/dl)
- Significant peripheral vascular disease
- Severe Raynaud's phenomenon
- Individuals unable to give informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Pilot Study Characterizing Aerobic Exercise in Women With Systemic Lupus Erythematosus (Exercise SLE Pilot).
Background:
As many as 1.5 million Americans are living with systemic lupus erythematosus (Lupus). Lupus makes people very tired. It also makes it hard for people to be physically active. Studies have shown that aerobic exercise training helps people with heart or lung illnesses be less tired and more active. Researchers want to use an exercise training program on people with Lupus to see if it has the same results.
Read more
Objectives:
To find out if aerobic exercise helps people with Lupus be less tired and more active.
Eligibility:
Women ages 21-80 who have Lupus and are not physically active.
Design:
Participants will be screened with a medical history and physical exam. They will have heart and lung tests, as well as blood and urine tests. They will also answer questions about their quality of life and take a test that measures lupus activity.
The study will last 14-16 weeks.
For the first two study visits, participants will do treadmill exercise tests and answer more quality of life questions. For these treadmill tests, participants will wear sensors, a mask, or a mouthpiece while they exercise.
Participants will then begin exercise training, 3 times a week for 12 weeks. At each of these visits, they will walk very fast for 30 minutes on a track or a treadmill. Each visit will last about 1 hour.
At the halfway point of the study, participants will repeat some of the screening tests. This visit will last about 3 hours.
At the end of the study, participants will repeat the screening tests. They will also repeat the treadmill exercise tests.
Read the detailed description
We propose a single-arm exploratory study to characterize the responses and adaptations to aerobic exercise in women who have mild to moderate systemic lupus erythematosus (SLE) uncomplicated by organ damage that would limit participation. This is a pilot study to provide additional preliminary data to support a future U01 application. Persistent, excessive fatigue is among the three most debilitating symptoms of SLE and is cited by as many as 50% of patients as the single most debilitating symptom. We have observed, in women with mild SLE, significant relationships among deficits in work capacity and oxygen consumption obtained during treadmill exercise and patient reported measures of fatigue severity. Clinically significant functional aerobic impairment was present in these women, suggesting an underlying pathophysiological limitation that restricted cardiorespiratory capacity to well below that expected to occur as a result of normal deconditioning due to a sedentary lifestyle and lack of physical activity. We have also observed prolonged rest to steady state metabolic transition during even submaximal exercise in women with SLE . At peak exercise, muscle oxygenation deficiency was apparent despite normal increases in central circulatory oxygen delivery to the active muscles. Muscle tissue studies in other laboratories have implicated muscle basal lamina thickening as an oxygen diffusion barrier, which could possibly diminish the rate of tissue oxygen uptake and restrict cardiorespiratory capacity. Aerobic exercise training could improve cardiorespiratory capacity in women with SLE and with that improvement precipitate a reduction in their fatigability, particularly if that fatigability is mediated by impaired cardiorespiratory function.
Our research team is uniquely qualified to undertake this research and is one of the few teams possessing the experience and background necessary for contributing to this novel, understudied, yet critical field of rehabilitation research. For example, in addition to Dr. Keyser's studies on cardiorespiratory dysfunction in women with SLE, our team has studied the effects of an intense aerobic exercise-training program in individuals who have pulmonary hypertension (PH) or interstitial lung disease (ILD), two conditions associated with autoimmune diseases such as SLE. In fact, several of the subjects had SLE and the majority had autoimmune diseases of somewhat similar etiology. Our results demonstrated improved cardiorespiratory function and diminished fatigability in these patients, without serious adverse events, following a 10-week regimen of intense aerobic exercise training. Adherence to the protocol was over 90% in both subject subsets and there were no serious adverse events in either of these groups.
Subjects of the proposed research will be between 21 and 80 years of age and living within a reasonable travel distance from the greater Washington D.C. area. Subjects will be recruited from the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Intramural Research Program (IRP) Lupus Clinics. All tests and exercise training will be conducted at the NIH Clinical Center. There will be a single treatment condition consisting of 12-weeks of supervised treadmill walking, three times a week, for 30 minutes per session, at an intensity of 70-80% of the subject's heart rate reserve.
The primary outcome measure for our trial will be the time taken to attain the anaerobic threshold, which is a performance marker of fatigability that is unaffected by patient motivation or perception. Secondary outcome variables will include other measures of cardiorespiratory capacity measured during a cardiopulmonary exercise test (CPET) with accompanying pulmonary gas exchange, central circulatory function (including heart function and an optional measures of peripheral blood flow), and muscle oxygenation analyses. A number of questionnaires will also be completed including: Fatigue Severity Scale, Patient Reported Outcomes Measurement Information System (PROMIS). All of these data will be obtained before and after aerobic exercise training.
Study Impact: Aerobic exercise is generally safe, inexpensive, and can easily be made available and accessible to almost everyone. It requires no approval by regulatory agencies and is thus available as a medically prescribed and supervised intervention almost immediately following confirmation of its safety and efficacy. Effective use of aerobic exercise training as a cardiorespiratory, rehabilitative intervention could have a high degree of impact on personal and public health outcomes.
- Being tested
- Treadmill exercise training
- Keywords
- Rehabilitation, Fatigue
- Medical subject headings
- Lupus Erythematosus, Systemic, Autoimmune Diseases, Rheumatic Diseases, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treadmill exercise trainingOther
30 minutes of continuous treadmill walking at a target intensity or use of an interval approach in which walking at the target will be sustained at smaller training interval durations of no shorter than 5 minutes followed by an active rest interval that is no longer than 1.5 times the training interval until the subject achieves a total exercise time of 30 minutes, excluding the rest intervals. Each session will last about 60 minutes but slightly longer if an interval approach is used.
| Study group | Role | What they receive |
|---|---|---|
| Aerobic exercise training (AET) | Experimental | Participants with systemic lupus erythematosus participated in a 12-week aerobic exercise training program. Exercise was performed on a treadmill, three times a week for 30 minutes at target training intensity of 70 - 80% of heart rate reserve [0.7 to 0.8 * (peak heart rate - resting heart rate) + resting heart rate] Receives: Other: Treadmill exercise training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Time Taken to Attain the Anaerobic Threshold (AT)
The anaerobic threshold (AT) is an objective measure of fatigability, and is determined from gas exchange variables during a cardiopulmonary exercise test (CPET). The effect of exercise training was examined by the change in the time taken to attain the AT by measuring the post-exercise training value minus the pre-exercise training value. A positive value indicates improvement in fatigability and a negative value indicates no improvement or worsening in fatigability. CPET measurement was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in the Time Constant for Oxygen Uptake Kinetics
The oxygen uptake kinetics is an objective measure of fatigability, determined from oxygen uptake measures during a square-wave exercise test. The time constant is the time taken to reach 63% of the steady state response. The effect of exercise training was examined by the change in the time constant by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in fatigability and a positive value indicates no improvement or worsening in fatigability. The square-wave exercise test was done before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Performance Fatigability Index (PerfFI)
The performance fatigability index (PerfFI) is a measure of fatigability. The PerfFI was determined during a 10-minute walk test (10MWT). The average velocity of 10MWT was divided by the average velocity achieved over the first 2.5 minutes (decline in performance), then further divided by the total distance walked on the 10MWT (an index of intensity) multiplied by 1000. The effect of exercise training was examined by the change in the PerfFI by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in fatigability and a positive value indicates no improvement or worsening in fatigability. The 10MWT measurement was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Perceived Fatigability Index (PercFI)
The perceived fatigability index (PercFI) is a measure of fatigability. The PercFI was determined during a 10-minute walk test (10MWT) by rating their perceive tiredness on a 7-point Likert scale after the test. The score is divided by the total distance walked on the 10MWT, multiplied by 1000. The effect of exercise training was examined by the change in the PerfFI by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in fatigability and a positive value indicates no improvement or worsening in fatigability. The 10MWT measurement was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Secondary outcomes (13)
Change in Muscle Oxygenation
Muscle oxygenation is indicated by tissue saturation index (TSI), which is the amount of oxygenated hemoglobin divided by total hemoglobin in percent. This is evaluated using near-infrared spectroscopy (NIRS) during the cardiopulmonary exercise test (CPET). Peak TSI is determined at the end of the CPET representing the lowest muscle oxygenation during volitional exercise. The effect of exercise training was examined by the change in peak TSI by measuring the post-exercise training value minus the pre-exercise training value. A negative value may indicate better muscle oxygenation capacity and a positive value may indicate no change or reduction in muscle oxygenation capacity. The CPET was performed before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Cardiac Function
Cardiac function is indicated by cardiac output, which is the amount of blood the heart pumps in 1 minute. It is defined mathematically as the product of the heart rate and cardiac stroke volume. This is measured using bioimpedance cardiography (a non-invasive method of capturing cardiodynamic variables) during the cardiopulmonary exercise test (CPET). Peak cardiac output is determined at the end of the CPET representing the highest cardiac output during volitional exercise. The effect of exercise training was examined by the change in peak cardiac output by measuring the post-exercise training value minus the pre-exercise training value. A positive value indicates improvement in cardiac function and a negative value indicates no change or worsening in cardiac function. The CPET was performed before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Fatigue Severity Scale (FSS)
The Fatigue Severity Scale (FSS) is a 9-item questionnaire that assesses fatigue severity on a 7-point Likert scale. The FSS score is an average of the total score for the 9-items, with a minimum of 1 and a maximum of 7. A higher FSS score indicate more fatigue severity. The effect of exercise training was examined by the change in FSS average scores by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in fatigue severity and a positive value indicates no improvement or worsening in fatigue severity. The FSS questionnaire was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Anxiety Domain
The PROMIS-57 profile is a self-reported questionnaire assessing quality of life in various domains. The anxiety domain is scored on a 5-point Likert scale and converted into standardized T-scores with a mean of 50 and a standard deviation of 10 based on a US general population. Higher scores indicate more anxiety being measured. The effect of exercise training was examined by the change in anxiety domain by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in anxiety and a positive value indicates no improvement or worsening in anxiety. The PROMIS-57 profile questionnaire was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Depression Domain
The PROMIS-57 profile is a self-reported questionnaire assessing quality of life in various domains. The depression domain is scored on a 5-point Likert scale and converted into standardized T-scores with a mean of 50 and a standard deviation of 10 based on a US general population. Higher scores indicate more depression being measured. The effect of exercise training was examined by the change in depression domain by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in depression and a positive value indicates no improvement or worsening in depression. The PROMIS-57 profile was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Fatigue Domain
The PROMIS-57 profile is a self-reported questionnaire assessing quality of life in various domains. The fatigue domain is scored on a 5-point Likert scale and converted into standardized T-scores with a mean of 50 and a standard deviation of 10 based on a US general population. Higher scores indicate greater fatigue. The effect of exercise training was examined by the change in fatigue domain by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in fatigue and a positive value indicates no improvement or worsening in fatigue. The PROMIS-57 profile questionnaire was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Physical Function Domain
The PROMIS-57 profile is a self-reported questionnaire assessing quality of life in various domains. The Physical Function domain is scored on a 5-point Likert scale and converted into standardized T-scores with a mean of 50 and a standard deviation of 10 based on a US general population. Higher scores indicate more physical function being measured. The effect of exercise training was examined by the change in physical function domain by measuring the post-exercise training value minus the pre-exercise training value. A positive value indicates improvement in physical function and a negative value indicates no improvement or worsening in physical function. The PROMIS-57 profile questionnaire was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Sleep Disturbance Domain
The PROMIS-57 profile is a self-reported questionnaire assessing quality of life in various domains. The Sleep Disturbance domain is scored on a 5-point Likert scale and converted into standardized T-scores with a mean of 50 and a standard deviation of 10 based on a US general population. Higher scores indicate more sleep disturbance being measured. The effect of exercise training was examined by the change in sleep disturbance domain by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in sleep disturbance and a positive value indicates no improvement or worsening in sleep disturbance. The PROMIS-57 profile questionnaire was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Ability to Participate in Social Roles and Activities Domain
The PROMIS-57 profile is a self-reported questionnaire assessing quality of life in various domains. The ability to participate in social roles and activities domain is scored on a 5-point Likert scale and converted into standardized T-scores with a mean of 50 and a standard deviation of 10 based on a US general population. Higher scores indicate more ability to participate in social roles and activities. The effect of exercise training was examined by the change in ability to participate in social roles and activities domain by measuring the post-exercise training value minus the pre-exercise training value. A positive value indicates improvement in ability to participate in social roles and activities and a negative value indicates no improvement or worsening in ability to participate in social roles and activities. The PROMIS-57 profile questionnaire was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Pain Interference Domain
The PROMIS-57 profile is a self-reported questionnaire assessing quality of life in various domains. The pain interference domain is scored on a 5-point Likert scale and converted into standardized T-scores with a mean of 50 and a standard deviation of 10 based on a US general population. Higher scores indicate more pain interference being measured. The effect of exercise training was examined by the change in pain interference domain by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in pain interference and a positive value indicates no improvement or worsening in pain interference. The PROMIS-57 profile questionnaire was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Pain Intensity Score
The PROMIS-57 profile is a self-reported questionnaire assessing quality of life in various domains. Pain intensity is scored from 0 to 10, with higher scores indicating greater pain intensity. The effect of exercise training was examined by the change in pain intensity domain by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in pain intensity and a positive value indicates no improvement or worsening in pain intensity. The PROMIS-57 profile questionnaire was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Safety of Estrogen in Lupus Erythematosus, National Assessment Modification of Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)
SELENA-SLEDAI is a 24-item weighted index measure of disease activity at time of assessment or in the preceding 10 days. It consists of clinical and laboratory variables, with a minimum score of 0 and maximum score of 105. Higher scores represent greater disease activity. The effect of exercise training was examined by the change in SELENA-SLEDAI by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in disease activity and a positive value indicates no improvement or worsening in disease activity. The SELENA-SLEDAI was assessed once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)
SLICC/ACR-DI is a 41-item instrument used to assess damage since lupus disease onset. Clinical assessment is made in 12 different organ systems, and a sum total from all organ scales are computed. A minimum score of 0 and a maximum score of 47 is possible with higher scores indicating more damage. The effect of exercise training was examined by the change in SLICC/ACR-DI by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates no change in damage since disease onset and a positive value indicates increase in damage since disease onset. The SLICC/ACR-DI was assessed before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Measured: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2017
- Study start22 Feb 2018
- Primary completion25 Feb 2021
- Study completion25 Feb 2021
Why it stopped: Research activities were suspended due to the COVID-19 pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Systemic Lupus ErythematosusStudies 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
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Leighton Chan, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03186794
- Sponsor's protocol ID
- 170111
- Other IDs
- 17-CC-0111
- Status last verified
- Mar 2021
- First submitted
- 13 Jun 2017
- Last updated
- 10 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Limited, de-identified samples may be available to other NIH intramural researchers.
Publications
Keyser RE, Rus V, Cade WT, Kalappa N, Flores RH, Handwerger BS. Evidence for aerobic insufficiency in women with systemic Lupus erythematosus. Arthritis Rheum. 2003 Feb 15;49(1):16-22. doi: 10.1002/art.10926.
PubMed 12579589Keyser RE, Rus V, Mikdashi JA, Handwerger BS. Exploratory study on oxygen consumption on-kinetics during treadmill walking in women with systemic lupus erythematosus. Arch Phys Med Rehabil. 2010 Sep;91(9):1402-9. doi: 10.1016/j.apmr.2010.06.003.
PubMed 20801259Carvalho MR, Sato EI, Tebexreni AS, Heidecher RT, Schenkman S, Neto TL. Effects of supervised cardiovascular training program on exercise tolerance, aerobic capacity, and quality of life in patients with systemic lupus erythematosus. Arthritis Rheum. 2005 Dec 15;53(6):838-44. doi: 10.1002/art.21605.
PubMed 16342102
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study Characterizing Aerobic Exercise in Women With Systemic Lupus Erythematosus (Exercise SLE Pilot).
- ClinicalTrials.gov ID
- NCT03186794
- Acronym / sponsor ID
- 170111
- Keywords
- Rehabilitation, Fatigue
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Research activities were suspended due to the COVID-19 pandemic
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- 22 Feb 2018 (actual)
- Primary completion
- 25 Feb 2021 (actual)
- Study completion
- 25 Feb 2021 (actual)
- First posted
- 14 Jun 2017 (actual)
- Results
- Posted 10 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
As many as 1.5 million Americans are living with systemic lupus erythematosus (Lupus). Lupus makes people very tired. It also makes it hard for people to be physically active. Studies have shown that aerobic exercise training helps people with heart or lung illnesses be less tired and more active. Researchers want to use an exercise training program on people with Lupus to see if it has the same results.
Objectives:
To find out if aerobic exercise helps people with Lupus be less tired and more active.
Eligibility:
Women ages 21-80 who have Lupus and are not physically active.
Design:
Participants will be screened with a medical history and physical exam. They will have heart and lung tests, as well as blood and urine tests. They will also answer questions about their quality of life and take a test that measures lupus activity.
The study will last 14-16 weeks.
For the first two study visits, participants will do treadmill exercise tests and answer more quality of life questions. For these treadmill tests, participants will wear sensors, a mask, or a mouthpiece while they exercise.
Participants will then begin exercise training, 3 times a week for 12 weeks. At each of these visits, they will walk very fast for 30 minutes on a track or a treadmill. Each visit will last about 1 hour.
At the halfway point of the study, participants will repeat some of the screening tests. This visit will last about 3 hours.
At the end of the study, participants will repeat the screening tests. They will also repeat the treadmill exercise tests.
Detailed description
We propose a single-arm exploratory study to characterize the responses and adaptations to aerobic exercise in women who have mild to moderate systemic lupus erythematosus (SLE) uncomplicated by organ damage that would limit participation. This is a pilot study to provide additional preliminary data to support a future U01 application. Persistent, excessive fatigue is among the three most debilitating symptoms of SLE and is cited by as many as 50% of patients as the single most debilitating symptom. We have observed, in women with mild SLE, significant relationships among deficits in work capacity and oxygen consumption obtained during treadmill exercise and patient reported measures of fatigue severity. Clinically significant functional aerobic impairment was present in these women, suggesting an underlying pathophysiological limitation that restricted cardiorespiratory capacity to well below that expected to occur as a result of normal deconditioning due to a sedentary lifestyle and lack of physical activity. We have also observed prolonged rest to steady state metabolic transition during even submaximal exercise in women with SLE . At peak exercise, muscle oxygenation deficiency was apparent despite normal increases in central circulatory oxygen delivery to the active muscles. Muscle tissue studies in other laboratories have implicated muscle basal lamina thickening as an oxygen diffusion barrier, which could possibly diminish the rate of tissue oxygen uptake and restrict cardiorespiratory capacity. Aerobic exercise training could improve cardiorespiratory capacity in women with SLE and with that improvement precipitate a reduction in their fatigability, particularly if that fatigability is mediated by impaired cardiorespiratory function.
Our research team is uniquely qualified to undertake this research and is one of the few teams possessing the experience and background necessary for contributing to this novel, understudied, yet critical field of rehabilitation research. For example, in addition to Dr. Keyser's studies on cardiorespiratory dysfunction in women with SLE, our team has studied the effects of an intense aerobic exercise-training program in individuals who have pulmonary hypertension (PH) or interstitial lung disease (ILD), two conditions associated with autoimmune diseases such as SLE. In fact, several of the subjects had SLE and the majority had autoimmune diseases of somewhat similar etiology. Our results demonstrated improved cardiorespiratory function and diminished fatigability in these patients, without serious adverse events, following a 10-week regimen of intense aerobic exercise training. Adherence to the protocol was over 90% in both subject subsets and there were no serious adverse events in either of these groups.
Subjects of the proposed research will be between 21 and 80 years of age and living within a reasonable travel distance from the greater Washington D.C. area. Subjects will be recruited from the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Intramural Research Program (IRP) Lupus Clinics. All tests and exercise training will be conducted at the NIH Clinical Center. There will be a single treatment condition consisting of 12-weeks of supervised treadmill walking, three times a week, for 30 minutes per session, at an intensity of 70-80% of the subject's heart rate reserve.
The primary outcome measure for our trial will be the time taken to attain the anaerobic threshold, which is a performance marker of fatigability that is unaffected by patient motivation or perception. Secondary outcome variables will include other measures of cardiorespiratory capacity measured during a cardiopulmonary exercise test (CPET) with accompanying pulmonary gas exchange, central circulatory function (including heart function and an optional measures of peripheral blood flow), and muscle oxygenation analyses. A number of questionnaires will also be completed including: Fatigue Severity Scale, Patient Reported Outcomes Measurement Information System (PROMIS). All of these data will be obtained before and after aerobic exercise training.
Study Impact: Aerobic exercise is generally safe, inexpensive, and can easily be made available and accessible to almost everyone. It requires no approval by regulatory agencies and is thus available as a medically prescribed and supervised intervention almost immediately following confirmation of its safety and efficacy. Effective use of aerobic exercise training as a cardiorespiratory, rehabilitative intervention could have a high degree of impact on personal and public health outcomes.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aerobic exercise training (AET) | Experimental | Other: Treadmill exercise trainingParticipants with systemic lupus erythematosus participated in a 12-week aerobic exercise training program. Exercise was performed on a treadmill, three times a week for 30 minutes at target training intensity of 70 - 80% of heart rate reserve [0.7 to 0.8 * (peak heart rate - resting heart rate) + resting heart rate] |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Fulfilling 4 of the 11 American College of Rheumatology Criteria for the Classification of Systemic Lupus Erythematosus
- Age 21 to 80
- Female Gender
- BMI less than 40
- No primary or secondary medical conditions that would limit aerobic capacity or make exercise participation unsafe. (These conditions are found under the exclusion criteria listed below and include cardiovascular disease and cardiomyopathy, pulmonary and pulmonary vascular disease, stroke, significant hepatic or renal dysfunction, most cancers, diabetes mellitus, HIV infection, and peripheral vascular disease.)
Key exclusion criteria (22 listed)
- Prednisone greater than or equal to 15 mg daily (or equivalent)
- Have started azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide or biologics within 3 months
- Rituximab infusion within 6 months
- Present symptoms of ischemic heart disease, right- or left-sided heart failure, cor pulmonale or pulmonary hypertension, dilated or hypertrophic cardiomyopathy or non- idiopathic cardiomyopathy
- Significant pulmonary dysfunction (obstructive, restrictive, or infectious pulmonary disease)
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 |
|---|---|---|
| Treadmill exercise training30 minutes of continuous treadmill walking at a target intensity or use of an interval approach in which walking at the target will be sustained at smaller training interval durations of no shorter than 5 minutes followed by an active rest interval that is no longer than 1.5 times the training interval until the subject achieves a total exercise time of 30 minutes, excluding the rest intervals. Each session will last about 60 minutes but slightly longer if an interval approach is used. | Other | Aerobic exercise training (AET) |
Primary outcome
Change in the Time Taken to Attain the Anaerobic Threshold (AT)
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
The anaerobic threshold (AT) is an objective measure of fatigability, and is determined from gas exchange variables during a cardiopulmonary exercise test (CPET). The effect of exercise training was examined by the change in the time taken to attain the AT by measuring the post-exercise training value minus the pre-exercise training value. A positive value indicates improvement in fatigability and a negative value indicates no improvement or worsening in fatigability. CPET measurement was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Change in the Time Constant for Oxygen Uptake Kinetics
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
The oxygen uptake kinetics is an objective measure of fatigability, determined from oxygen uptake measures during a square-wave exercise test. The time constant is the time taken to reach 63% of the steady state response. The effect of exercise training was examined by the change in the time constant by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in fatigability and a positive value indicates no improvement or worsening in fatigability. The square-wave exercise test was done before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Change in Performance Fatigability Index (PerfFI)
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
The performance fatigability index (PerfFI) is a measure of fatigability. The PerfFI was determined during a 10-minute walk test (10MWT). The average velocity of 10MWT was divided by the average velocity achieved over the first 2.5 minutes (decline in performance), then further divided by the total distance walked on the 10MWT (an index of intensity) multiplied by 1000. The effect of exercise training was examined by the change in the PerfFI by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in fatigability and a positive value indicates no improvement or worsening in fatigability. The 10MWT measurement was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
Change in Perceived Fatigability Index (PercFI)
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
The perceived fatigability index (PercFI) is a measure of fatigability. The PercFI was determined during a 10-minute walk test (10MWT) by rating their perceive tiredness on a 7-point Likert scale after the test. The score is divided by the total distance walked on the 10MWT, multiplied by 1000. The effect of exercise training was examined by the change in the PerfFI by measuring the post-exercise training value minus the pre-exercise training value. A negative value indicates improvement in fatigability and a positive value indicates no improvement or worsening in fatigability. The 10MWT measurement was done once before the start of the 12-week exercise program (pre) and repeated at the end of the 12-week exercise program (post).
13 secondary outcomes
Change in Muscle Oxygenation
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Cardiac Function
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Fatigue Severity Scale (FSS)
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Anxiety Domain
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Depression Domain
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Fatigue Domain
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Physical Function Domain
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Sleep Disturbance Domain
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Ability to Participate in Social Roles and Activities Domain
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Pain Interference Domain
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Pain Intensity Score
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Safety of Estrogen in Lupus Erythematosus, National Assessment Modification of Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Change in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)
Time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12579589Keyser RE, Rus V, Cade WT, Kalappa N, Flores RH, Handwerger BS. Evidence for aerobic insufficiency in women with systemic Lupus erythematosus. Arthritis Rheum. 2003 Feb 15;49(1):16-22. doi: 10.1002/art.10926.
- Background: PubMed 20801259Keyser RE, Rus V, Mikdashi JA, Handwerger BS. Exploratory study on oxygen consumption on-kinetics during treadmill walking in women with systemic lupus erythematosus. Arch Phys Med Rehabil. 2010 Sep;91(9):1402-9. doi: 10.1016/j.apmr.2010.06.003.
- Background: PubMed 16342102Carvalho MR, Sato EI, Tebexreni AS, Heidecher RT, Schenkman S, Neto TL. Effects of supervised cardiovascular training program on exercise tolerance, aerobic capacity, and quality of life in patients with systemic lupus erythematosus. Arthritis Rheum. 2005 Dec 15;53(6):838-44. doi: 10.1002/art.21605.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Limited, de-identified samples may be available to other NIH intramural researchers.
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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.
Leighton Chan, M.D. principal investigator
National Institutes of Health Clinical Center (CC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Treadmill exercise training in people with Systemic Lupus Erythematosus and Lupus, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
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 11 inclusion and 22 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: stopped early, as of the sponsor's last update on 10 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Yes. Results are posted in the registry (first posted 10 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in the Time Taken to Attain the Anaerobic Threshold (AT) (time frame: Before 12-week intervention (Pre) and after 12-week intervention (Post)). The study lists 4 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 NCT03186794, which also lists 3 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 10 May 2022.