Exercise and Nutrition Recommendations for Patients Using Glucocorticoids (ENRG)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Other: Exercise Training

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bruno Gualano, PhD; Phone Number: 551126618022; Email: gualano@usp.br
• Study Contact Backup: Name: Eimear Dolan, PhD; Phone Number: +447934771844; Email: eimeardolan@usp.br

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403-000
    • Recruiting
    • Clinical Hospital of the School of Medicine, University of Sao Paulo
    • Contact: Bruno Gualano, PhD; Phone Number: 551126618022; Email: gualano@usp.br
    • Contact: Eimear Dolan, PhD; Phone Number: +447934771844; Email: eimeardolan@usp.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise training; 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; 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.
No Intervention: Control; The control group will receive standard medical care.

What is the study measuring?

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).

Collaborators and Investigators

• Sponsor: Bruno Gualano
• Investigators: Principal Investigator: Eimear Dolan, PhD, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2021
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: September 10, 2021
• First Submitted That Met QC Criteria: October 11, 2021
• First Posted (Actual): October 22, 2021

Study Record Updates

• Last Update Posted (Actual): October 22, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: exercise; training; glucocorticoids; autoimmune
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: The ENRG Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: On study completion, and once data has been analysed and submitted for publication, anonymised individual participant data for all outcomes will be made available.
• IPD Sharing Time Frame: Anonymised data will be made permanently available upon study completion and once data has been analysed and submitted for publication.
• IPD Sharing Access Criteria: Anonymised data will be accessible to anyone interested via online repositories.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No