http://www.biomedcentral.com/1471-2431/15/117
(open access)
(open access)
Research article
Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial
Even Fagermoen12*, Dag Sulheim34, Anette Winger5, Anders M. Andersen6, Johannes Gjerstad78, Kristin Godang9, Peter C. Rowe10, J. Philip Saul11, Eva Skovlund1213 andVegard Bruun Wyller114 *Corresponding author: Even Fagermoen feef@online.no
BMC Pediatrics 2015, 15:117 doi:10.1186/s12887-015-0428-2
The electronic version of this article is the complete one and can be found online at:http://www.biomedcentral.com/1471-2431/15/117
Received: 7 September 2014
Accepted: 20 August 2015
Published: 10 September 2015
© 2015 Fagermoen et al.
Abstract
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 alpha 2A –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.
Trial registration
Clinical Trials ID: NCT01040429, date of registration 12/28/2009.