Clinical trial NCT03186794: Aerobic Exercise in Women With Systemic Lupus Erythematosus
Official title: Pilot Study Characterizing Aerobic Exercise in Women With Systemic Lupus Erythematosus (Exercise SLE Pilot).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Systemic Lupus Erythematosus
Lupus
Autoimmune Disease
Rheumatic Disease
Keywords: Rehabilitation
Fatigue
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2017-06-14
Enrollment: 24
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief 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. 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.

Eligibility criteria: INCLUSION CRITERIA:

* 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).
* 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

EXCLUSION CRITERIA:

* 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)
* 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

Primary outcomes:
measure: Change in the Time Taken to Attain the Anaerobic Threshold (AT)
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in the Time Constant for Oxygen Uptake Kinetics
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Performance Fatigability Index (PerfFI)
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Perceived Fatigability Index (PercFI)
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Secondary outcomes:
measure: Change in Muscle Oxygenation
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Cardiac Function
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Fatigue Severity Scale (FSS)
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Anxiety Domain
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Depression Domain
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Fatigue Domain
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Physical Function Domain
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Sleep Disturbance Domain
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Ability to Participate in Social Roles and Activities Domain
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Pain Interference Domain
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Patient Reported Outcomes Measurement Information System (PROMIS-57 Profile): Pain Intensity Score
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Safety of Estrogen in Lupus Erythematosus, National Assessment Modification of Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
measure: Change in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)
timeFrame: Before 12-week intervention (Pre) and after 12-week intervention (Post)
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institutes of Health Clinical Center (CC)
name: Leighton Chan, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Keyser 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.
citation: Carvalho 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.