Randomized controlled single-center clinical trial of high-intensity interval training in patients with systemic lupus erythematosus

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by elevated levels of type 1 interferons (IFN-1). Along with relapses, patients experience persistent fatigue and reduced aerobic capacity. This study investigates how high-intensity interval training (HIIT) affects fatigue and aerobic capacity in SLE patients and whether IFN-1 influences these outcomes. METHODS: Fifty-three SLE patients were randomly assigned in a 1:1 ratio to either thrice-weekly HIIT sessions (21 women and 5 men) or no intervention (25 women and 2 men) for 12 weeks. The co-primary outcomes were aerobic capacity (ml O2/min/kg) and fatigue, measured by the Fatigue Severity Scale (FSS). The average treatment effects and their modification by a peripheral blood expression score of IFN-1-regulated genes were evaluated using constrained, adjusted linear mixed models. RESULTS: The HIIT intervention increased aerobic capacity by an average of 2.31 ml/kg/min compared to the control group (97.5% CI: 0.55 to 4.1; adjusted p = 0.008). However, HIIT reduced the FSS score by only 0.11 points compared to the control group (97.5% CI: -0.52 to 0.74; adjusted p > 0.99). In exploratory analyses, higher IFN-1 scores were linked to poorer HIIT outcomes, particularly regarding aerobic capacity (-0.55 ml/kg/min per SD of IFN-1 score; 95% CI: -1.37 to 0.26, adj-p = 0.295) and FSS score (0.29 per SD of IFN-1 score; CI: 0.004 to 0.58, adj-p = 0.117). However, due to multiple testing, we cannot rule out that these modifying effects may be due to chance. CONCLUSION: Twelve weeks of HIIT significantly increased the aerobic capacity of SLE patients but did not alleviate fatigue. In exploratory analyses, high IFN-1 expression scores were negatively associated with HIIT outcomes, but further studies are needed to confirm this finding. TRIAL SPONSOR: Centre for Physical Activity Research (CFAS), Rigshospitalet, Denmark. CLINICAL TRIAL REGISTRATION: NCT05478018.