Acute Response to Exercise in Patients With Rheumatoid Arthritis

Impact of Interleukin-6 Receptor Blockade on Acute Response to Exercise on Insulin Sensitivity and Muscle Glucose Uptake in Patients With Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the joints, causing pain, edema, physical disability and poor quality of life. In addition, RA patients are at increased risk of developing cardiovascular disease (CVD) and premature death. The most effective pharmacological treatment is the use of biological agents that inhibit the action of specific substances, such as interleukin 6 (IL-6) and tumor necrosis factors (TNF). Physical exercise is considered a first-line non-pharmacological treatment in RA, improving inflammatory and metabolic profile, functional capacity, fatigue and preventing the onset of CVD. There is evidence that IL-6, when secreted as a result of exercise, brings several benefits. However, there is no study investigating the interaction between biological IL-6 blocking agents and exercise on metabolic responses, such as insulin sensitivity and glucose uptake, in patients with RA. To answer this question, adult women diagnosed with RA and healthy controls will be recruited for an acute session of exercise. RA patients will be divided into 2 groups, according to the pharmacological treatment (tocilizumab or anti-TNF). The acute responses of insulin sensitivity after an acute session of exercise will be assessed by the hyperinsulinemic euglycemic clamp, and the molecular pathways will be assessed by muscle biopsy and gene and protein expression analysis. Positron emission tomography-magnetic resonance imaging (PET/MRI) will be performed to quantify skeletal muscle glucose uptake.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Behavioral: Exercise

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05508-030
    • Recruiting
    • Univsersity of Sao Paulo
    • Contact: Bruno Gualano, PhD; Phone Number: 551126618022; Email: gualano@usp.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Adult women diagnosed with rheumatoid arthritis under pharmacological treatment, for at least 6 months, with a monoclonal antibody against the interleukin-6 receptor or TNF-alpha inhibitors;
• Stable dose of monoclonal antibody against the interleukin-6 receptor or TNF-alpha inhibitors in the previous 3 months;

Exclusion Criteria:

• Any physical limitation or disability that preclude exercise participation;
• Participation in a structured exercise program in the previous 12 months;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IL-6 blockade; RA patients under pharmacological treatment with interleukin-6 blockade.	Behavioral: Exercise; Thirty minutes of aerobic exercise in a treadmill.
Experimental: Anti-TNF-alpha; RA patients under pharmacological treatment with anti-TNF-alpha.	Behavioral: Exercise; Thirty minutes of aerobic exercise in a treadmill.
Experimental: Healthy controls; Healthy participants.	Behavioral: Exercise; Thirty minutes of aerobic exercise in a treadmill.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Acute effect of exercise on insulin sensitivity assessed by the hyperinsulinemic euglycemic clamp.	1 hour post-exercise

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity-related molecular pathway (Western Blotting)	Insulin sensitivity-related molecular pathway will be assessed by Western Blotting.	Baseline and 4 hours post-exercise
Insulin sensitivity-related molecular pathway (RT-PCR)	Insulin sensitivity-related molecular pathway will be assessed by Real-Time Polymerase Chain Reaction (RT-PCR).	Baseline and 4 hours post-exercise
Skeletal muscle glucose uptake	Positron emission tomography-magnetic resonance imaging (PET/MRI) will be performed to quantify skeletal muscle glucose uptake.	3 hours post-exercise

Collaborators and Investigators

• Sponsor: University of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2021
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 8, 2021
• First Posted (Actual): June 16, 2021

Study Record Updates

• Last Update Posted (Actual): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: IL-6 blockade and exercise

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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