Home-Based Exercise Training in Childhood-Onset Takayasu Arteritis: A Multicenter, Randomized, Controlled Trial

Abstract

Introduction: Childhood-onset Takayasu Arteritis (c-TA) is a rare, large-vessel vasculitis seen in children that could predisposing patients to a high risk of mortality. Exercise has the potential to improve overall health in several diseases, but evidence remains scant in c-TA. The main objective of this study was to investigate the safety and potential therapeutic effects of exercise in c-TA.

Methods: This was a 12-week, multicenter, randomized, controlled trial, to test the effects of a home-based, exercise intervention vs. standard of care in c-TA patients in remission. The primary outcomes were arterial inflammation, assessed by [18F] FDG- PET/MRI and systemic inflammatory markers. Secondary outcomes included, physical activity levels, functionality, body composition, disease-related parameters, and quality of life.

Results: Thirty-seven patients were assessed for eligibility, which represents the total number of c-TA patients being followed by the three specialized medical ambulatory services in Sao Paulo. After exclusions, fourteen c-TA patients (71.4% females) aged 12-25 years were randomly allocated into exercised (n=5) and non-exercised groups (n=9). Exercise did not exacerbate arterial inflammation. In fact, exercised patients had a reduction in the frequency of vessel segments with severe inflammation, whereas the non-exercised patients had an opposite response (P=0.007). Greater improvements in visceral fat, steps per day, functionality and physical component SF-36 were observed in the exercised patients (P ≤ 0.05).

Conclusions: Exercise is safe and may improve visceral fat, physical activity levels, functionality, and physical component SF-36 in c-TA patients. Thus, exercise arises as a novel, evidence-based intervention to improve general health in c-TA.

Clinical trial registration: https://www.clinicaltrials.gov/ct2/show/NCT03494062?term=NCT03494062&draw=2&rank=1, identifier NCT03494062.

Keywords: arterial inflammation; cardiovascular risk; physical activity; physical exercise; vasculitis

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Astley, Clemente, Terreri, Carneiro, Lima, Buchpiguel, Leão Filho, de Sá Pinto, Silva, Campos, Aikawa, Gil, Pereira, Roschel and Gualano.

Figures

Figure 1

Flow diagram.

Figure 2

Illustrative case of a 17-year-old female patient with childhood-onset Takayasu Arteritis. Left: Angioresonance of aorta and its branches after intravenous administration of gadolinium. Arrows indicates an occlusion at the third portion of the brachiocephalic trunk. Right: Arterial inflammation grade III as assessed by 18F-fluorodeoxyglucose-positron emission tomography/magnetic resonance image at the brachiocephalic trunk (SUVmax=2.38).

Figure 3

Panel (A): Distribution of vessel segments in grade III, representing severe inflammation. P=0.007 for between-group comparison at POST. Panel (B): Illustrative case of a 20-year-old patient with childhood-onset Takayasu Arteritis. The [18F] FDG PET/MR imaging revealed grade III inflammation in the ascending aorta artery before the intervention (SUVmax=3.41). Following the exercise training program, the uptake decreased to grade II (SUVmax=2.61).

Figure 4

Overview of the changes in severe arterial inflammation, visceral fat mass, IL1-β, and number of steps following a 12-week, home-based, exercise training program or control (no exercise) in c-TA patients. Noticeably, the exercise-induced amelioration in severe arterial inflammation was mirrored by decreases in visceral fat and IL-1β levels (tendency towards significance) and increases in physical activity. The hypothesis raised by this study that these responses might be interrelated should be tested by larger trials.