TY - JOUR
T1 - Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue
T2 - A randomized controlled trial
AU - Fagermoen, Even
AU - Sulheim, Dag
AU - Winger, Anette
AU - Andersen, Anders M.
AU - Gjerstad, Johannes
AU - Godang, Kristin
AU - Rowe, Peter C.
AU - Saul, J. Philip
AU - Skovlund, Eva
AU - Wyller, Vegard Bruun
N1 - Funding Information:
We thank Kari Gjersum for secretary assistance; Hamsana Chandrakumar, Esther Gangsø, Anne Marie Halstensen, Adelheid Holm, Berit Widerøe Njølstad, Pelle Rohdin, and Anna Marie Thorendal Ryenbakken for practical assistance; Berit Bjelkåsen for development of the computerized randomization procedure; Liv Thrane Bjerke for pharmacy services; Gaute Døhlen, Bjørn Bendz, Knut Engedal, and Ola Didrik Saugstad for study monitoring; all referring units; and finally all participants and their parents/ next-of-kin. The study was funded by: Health South–East Hospital Trust; The University of Oslo; Oslo and Akershus University College of Applied Sciences; The Norwegian Competence Network of Paediatric Pharmacotherapy; Simon Fougner Hartmann’s Family Foundation; Eckbo’s Family Foundation.
Publisher Copyright:
© 2015 Fagermoen et al.
PY - 2015/9/10
Y1 - 2015/9/10
N2 - 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. Trial registration: Clinical Trials ID: NCT01040429 , date of registration 12/28/2009.
AB - 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. Trial registration: Clinical Trials ID: NCT01040429 , date of registration 12/28/2009.
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U2 - 10.1186/s12887-015-0428-2
DO - 10.1186/s12887-015-0428-2
M3 - Article
C2 - 26357864
AN - SCOPUS:84941215060
SN - 1471-2431
VL - 15
JO - BMC Pediatrics
JF - BMC Pediatrics
IS - 1
M1 - 117
ER -