Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial
Fagermoen, Even; Sulheim, Dag; Winger, Anette; Andersen, Anders M.; Gjerstad, Johannes; Godang, Kristin; Rowe, Peter C.; Saul, J. Philip; Skovlund, Eva; Wyller, Vegard Bruun
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2015-10-09Metadata
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Fagermoen, E., Sulheim, D., Winger, A., Andersen, A.M., Gjerstad, J., Godang, K. ... Wyller, V.B. (2015). Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial. BMC Pediatrics, 15:117, doi: 10.1186/s12887-015-0428-2 http://dx.doi.org/10.1186/s12887-015-0428-2Abstract
Background: Chronic Fatigue Syndrome (CFS) is a common and disabling condition in adolescence with few
treatment options. A central feature of CFS is orthostatic intolerance and abnormal autonomic cardiovascular
control characterized by sympathetic predominance. We hypothesized that symptoms as well as the underlying
pathophysiology might improve by treatment with the alpha2A–adrenoceptor agonist clonidine.
Methods: A total of 176 adolescent CFS patients (12–18 years) were assessed for eligibility at a single referral center
recruiting nation-wide. Patients were randomized 1:1 by a computer system and started treatment with clonidine
capsules (25 μg or 50 μg twice daily, respectively, for body weight below/above 35 kg) or placebo capsules for
9 weeks. Double-blinding was provided. Data were collected from March 2010 until October 2012 as part of The
Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial
(NorCAPITAL). Effect of clonidine intervention was assessed by general linear models in intention-to-treat analyses,
including baseline values as covariates in the model.
Results: A total of 120 patients (clonidine group n = 60, placebo group n = 60) were enrolled and started treatment.
There were 14 drop-outs (5 in the clonidine group, 9 in the placebo group) during the intervention period. At 8 weeks,
the clonidine group had lower plasma norepinephrine (difference = 205 pmol/L, p = 0.05) and urine norepinephrine/
creatinine ratio (difference = 3.9 nmol/mmol, p = 0.002). During supine rest, the clonidine group had higher heart rate
variability in the low-frequency range (LF-HRV, absolute units) (ratio = 1.4, p = 0.007) as well as higher standard deviation
of all RR-intervals (SDNN) (difference = 12.0 ms, p = 0.05); during 20° head-up tilt there were no statistical differences in
any cardiovascular variable. Symptoms of orthostatic intolerance did not change during the intervention period.
Conclusions: Low-dose clonidine reduces catecholamine levels in adolescent CFS, but the effects on autonomic
cardiovascular control are sparse. Clonidine does not improve symptoms of orthostatic intolerance.