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Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial.

ABSTRACT: Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO2, chronotropic reserve (CR), and the heart rate recovery (?HRR) (that is, the difference between HR at peak exercise and at both the first (?HRR1) and second (?HRR2) minutes of recovery after exercise).The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO2 (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ?HRR1 and ?HRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.NCT01515163.

SUBMITTER: Prado DM

PROVIDER: S-EPMC3672722 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial.

Prado Danilo M L DM Benatti Fabiana B FB de Sá-Pinto Ana L AL Hayashi Ana P AP Gualano Bruno B Pereira Rosa M R RM Sallum Adriana M E AM Bonfá Eloisa E Silva Clovis A CA Roschel Hamilton H

Arthritis research & therapy 20130326 2

<h4>Introduction</h4>Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.<h4>Methods</h4>Nine ...[more]

PMID: 23531226

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Project description:ObjectiveTo determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment, and to investigate the safety of triptorelin.MethodsIn this randomized, double-blind, placebo-controlled, dose-escalation study, female patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 μg/kg, and the dose was escalated until complete ovarian suppression was maintained. The primary outcome was the weight-adjusted dose of triptorelin that provided complete ovarian suppression in at least 90% of the patients, as determined by gonadotropin-releasing hormone agonist stimulation testing. The secondary outcome was the period of time required to achieve ovarian suppression, as measured by unstimulated follicle-stimulating hormone and luteinizing hormone levels after the initiation of triptorelin treatment.ResultsTreatment with triptorelin at a weight-adjusted dose of 120 μg/kg body weight provided sustained complete ovarian suppression in 90% of the patients. After administration of the initial dose of triptorelin, 22 days were required to achieve complete ovarian suppression. The rates of adverse events (AEs) and serious adverse events (SAEs) per 100 patient-months of followup were not higher in the triptorelin group compared with the placebo group (for AEs, 189 versus 362; for SAEs, 2.1 versus 8.5).ConclusionHigh doses of triptorelin are needed to achieve and maintain complete ovarian suppression, but such doses appear to be well tolerated in adolescent female patients with childhood-onset SLE. Our data suggest that a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued.

Project description:Systemic lupus erythematosus (SLE) patients may show increased insulin resistance (IR) when compared with their healthy peers. Exercise training has been shown to improve insulin sensitivity in other insulin-resistant populations, but it has never been tested in SLE. Therefore, the aim of the present study was to assess the efficacy of a moderate-intensity exercise training program on insulin sensitivity and potential underlying mechanisms in SLE patients with mild/inactive disease. A 12-week, randomized controlled trial was conducted. Nineteen SLE patients were randomly assigned into two groups: trained (SLE-TR, n?=?9) and non-trained (SLE-NT, n?=?10). Before and after 12?weeks of the exercise training program, patients underwent a meal test (MT), from which surrogates of insulin sensitivity and beta-cell function were determined. Muscle biopsies were performed after the MT for the assessment of total and membrane GLUT4 and proteins related to insulin signaling [Akt and AMP-activated protein kinase (AMPK)]. SLE-TR showed, when compared with SLE-NT, significant decreases in fasting insulin [-39 vs. +14%, p?=?0.009, effect size (ES)?=?-1.0] and in the insulin response to MT (-23 vs. +21%, p?=?0.007, ES?=?-1.1), homeostasis model assessment IR (-30 vs. +15%, p?=?0.005, ES?=?-1.1), a tendency toward decreased proinsulin response to MT (-19 vs. +6%, p?=?0.07, ES?=?-0.9) and increased glucagon response to MT (+3 vs. -3%, p?=?0.09, ES?=?0.6), and significant increases in the Matsuda index (+66 vs. -31%, p?=?0.004, ES?=?0.9) and fasting glucagon (+4 vs. -8%, p?=?0.03, ES?=?0.7). No significant differences between SLT-TR and SLT-NT were observed in fasting glucose, glucose response to MT, and insulinogenic index (all p?>?0.05). SLE-TR showed a significant increase in AMPK Thr 172 phosphorylation when compared to SLE-NT (+73 vs. -12%, p?=?0.014, ES?=?1.3), whereas no significant differences between groups were observed in Akt Ser 473 phosphorylation, total and membrane GLUT4 expression, and GLUT4 translocation (all p?>?0.05). In conclusion, a 12-week moderate-intensity aerobic exercise training program improved insulin sensitivity in SLE patients with mild/inactive disease. This effect appears to be partially mediated by the increased insulin-stimulated skeletal muscle AMPK phosphorylation. Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT01515163.

Project description:OBJECTIVE: To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features. METHODS: We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay. RESULTS: We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33 ± 4.50), 64 first-degree relatives (mean age 39.95 ± 5.66), and 57 healthy (mean age 19.30 ± 4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their first-degree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels. CONCLUSION: Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.

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Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial.

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Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial.

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