Aerobic Exercise in Women With Systemic Lupus Erythematosus

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 21 Years - 80 Years
Gender Female
More Inclusion & Exclusion 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.
  • - 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 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 Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03186794
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

National Institutes of Health Clinical Center (CC)
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Leighton Chan, M.D.
Principal Investigator Affiliation National Institutes of Health Clinical Center (CC)
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

NIH
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Systemic Lupus Erythematosus, Lupus, Autoimmune Disease, Rheumatic Disease
Study Website: View Trial Website
Additional Details

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/NIAMS 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.

Arms & Interventions

Arms

Experimental: SLE Exercise

We propose to enroll 20 sedentary, adult, women with negligible to mild SLE disease activity (SELENA-SLEDAI less than or equal to 4) in this pilot study. Subjects must also have a Fatigue Severity Scale (FSS) composite score less than or equal to 4.0. We will restrict our recruitment to women with SLE as this is a small pilot study and would like to eliminate possible gender-biased confounders of physical activity (approximately 90% of patients with SLE are women).

Interventions

Other: - Treadmill exercise training

The target training heart rate range is 70-80% of heart rate reserve, computed as: 0.7 and 0.85 (peak heart rate minus resting heart rate) + resting heart rate. Subjects will exercise for 30 minutes per session, completing on average 3 sessions per week, over approximately 12 weeks. During the training session, heart rate, treadmill speed, treadmill inclination, perceived fatigability index and RPE will be recorded. In the event that subjects cannot sustain 30 minutes of continuous treadmill walking at the target intensity, an interval approach will be used 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 of these sessions will last about 60 minutes but slightly longer if an interval approached is used.

Contact a Trial Team

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Bethesda, Maryland

Status

Recruiting

Address

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

Site Contact

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

prpl@cc.nih.gov

800-411-1222 #TTY8664111010