Exercise and Nutrition Recommendations for Patients Using Glucocorticoids (ENRG)

Study Overview
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Brief Summary
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This parallel-group randomized, controlled, clinical trial aims to investigate the influence of a 6-month home-based, remotely-monitored, exercise training intervention on musculoskeletal health in patients with Systemic Lupus Erythematosus who have undergone glucocorticoid pulse therapy.

Detailed Description
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Glucocorticoid treatment is a frequently prescribed to individuals with autoimmune diseases, such as Systemic Lupus Erythematosus, due to its anti-inflammatory effects. This treatment strategy has proven clinical benefits, but it can also adversely influence musculoskeletal health. Glucocorticoid pulse therapy is a particularly intensive treatment strategy, commonly used when the disease state is at its most active. Patients who undergo pulse therapy have a high risk of muscle and bone loss, and exercise training is a promising adjunct therapy to potentially ameliorate these adverse effects, but the feasibility and efficacy of this approach has yet to be investigated. The aim of this study, therefore, is to conduct a parallel-group, controlled, randomized clinical trial, to investigate the feasibility and efficacy of a home-based, remotely-monitored, exercise training intervention on musculoskeletal health in patients with Systemic Lupus Erythematosus who have undergone glucocorticoid pulse therapy.

Official Title
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The Influence of Exercise Training on Musculoskeletal Health in Patients With Systemic Lupus Erythematosus Who Undergo Glucocorticoid Pulse Therapy

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Other: Exercise Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal women aged 18 to 45 diagnosed with Systemic Lupus Erythematosus according to SLICC criteria; Medical indication and prescription for glucocorticoid pulse therapy; Access to Internet and any device that allows for participation in exercise training online lessons (such as smart phone, laptop or personal computer); Willingness to participate in an exercise training program. Exclusion Criteria: Any physical, mental, neurological or musculoskeletal health impairment that contra-indicates exercise training. Use of medical therapy that alters bone metabolism, such as bisphosphonates, teriparatide and denosumab; Receiving prescription for multiple glucocorticoid pulse therapies mid-intervention; Being currently enrolled or having enrolled in a structured exercise training program in the last 6 months (defined as at least 2 planned, structures sessions of exercise training per week); Having a vertebral fracture at the moment of enrollment (identified by Vertical Fracture Assessment), or high risk for fracture (defined as low hip or spine bone mass [z-score < -3] or history of fragility fractures).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study comprises a 6-month parallel-group, randomized, controlled trial, in which individuals with Systemic Lupus Erythematosus who have undergone glucocorticoid pulse therapy (500-1000mg/d methylprednisolone i.v., 1-3 days), will be randomized into one of two conditions: control, consisting of no intervention and standard medical care; and exercise training, consisting of standard medical care supplemented by a twice-weekly, home-based, remotely monitored exercise training program. Patients will be assessed at three timepoints, namely 1-3 weeks after pulse therapy (according to patient's health state and willingness, PRE); three months after baseline (MID); and six months after baseline (POST).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise training<br>The experimental arm will enroll in a 6-month, twice-weekly, home-based, remotely monitored exercise training program, the emphasis of which will be to improve musculoskeletal health and function. | Other: Exercise Training<br>* The present intervention will consist of a 6-month long, twice-weekly, home-based, monitored exercise training program, with training sessions lasting around 40 minutes, with 48 sessions in total. The program will be delivered in the form of 6 x 4-week blocks, which will progressively increase in intensity and complexity, as the participants physical capacities develop. Additionally, and in addition with current physical activity guidelines, participants will be instructed to perform at least an additional 70 minutes of purposeful activities per week. Study trainers will discuss the content of these activities with each individual participant to facilitate selection of suitable activities (e.g., brisk walking, jogging, stair climbing or bike riding), but their selection will be left to the discretion of the individual participants, and activity logs will be maintained throughout the study period.<br>|
| No Intervention: Control<br>The control group will receive standard medical care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone health | Assessed by dual-energy X-ray absorptiometry, high resolution peripheral quantitative computed tomography and blood bone biomarkers (C-terminal telopeptide [β-CTX-1], procollagen type 1 amino-terminal propeptide [P1NP], sclerostin, osteocalcin). | Baseline (PRE), after 3 months (MID), and after 6 months (POST). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle health | Assessed by dual-energy X-ray absorptiometry (fat-free mass), one-repetition maximum test (bench press and leg extension), and muscle functionality tests (timed-up-and-go, timed-stands, handgrip). | Baseline (PRE), after 3 months (MID), and after 6 months (POST). | 
| Aerobic capacity | Assessed by maximal graded ergospirometric test. | Baseline (PRE), after 3 months (MID), and after 6 months (POST). | 
| Body composition | Assessed by dual-energy X-ray absorptiometry (fat mass, percentage body fat, lean mass), body mass index, waist and hip circumferences. | Baseline (PRE), after 3 months (MID), and after 6 months (POST). | 
| Intervention feasibility and acceptability | Assessed by feasibility metrics: Recruitment Capacity, Acceptability and Suitability, Resources, and Intervention Efficacy. | Entire study duration. | 
| Cardiovascular risk | Assessed by Framingham Risk Score | Baseline (PRE), after 3 months (MID), and after 6 months (POST). | 
| Proinflammatory cytokines | Assessed by interferon gamma (IFN-γ), interleukin 10 and 6 (IL-10, IL-6), tumor necrosis factor alpha (TNF-α), and soluble TNF receptors (sTNFR1 e sTNFR2) assays. | Baseline (PRE), after 3 months (MID), and after 6 months (POST). | 
| Nutritional intake | Assessed by three non-consecutive food recalls. | Baseline (PRE), after 3 months (MID), and after 6 months (POST). | 
| Disease activity | Assessed by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). | Baseline (PRE), after 3 months (MID), and after 6 months (POST). | 
| General quality of life | 36-Item Short Form Survey (SF-36). | Baseline (PRE), after 3 months (MID), and after 6 months (POST). | 
| Disease-related quality of life | Assessed by Systemic Lupus Erythematosus Quality of Life Questionnaire (SLEQOL) | Baseline (PRE), after 3 months (MID), and after 6 months (POST). | 
| Physical activity levels | Assessed by International Physical Activity Questionnaire (IPAQ) | Baseline (PRE), after 3 months (MID), and after 6 months (POST). | 
| Current and past bone-loading physical activity levels | Assessed by Bone-Specific Physical Activity Questionnaire (BPAQ). | Baseline (PRE). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, autoimmune, training, glucocorticoids