The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL)

• ClinicalTrials.gov Identifier: NCT01040429
• Recruitment Status: Completed
• First Posted: December 29, 2009
• Last Update Posted: November 20, 2012
• Sponsor: Oslo University Hospital
• Information provided by (Responsible Party): Vegard Bruun Wyller, Oslo University Hospital

Tracking Information

• First Submitted Date: December 28, 2009
• First Posted Date: December 29, 2009
• Last Update Posted Date: November 20, 2012
• Study Start Date: February 2010
• Actual Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 28, 2009): Mean steps/day count during one week [ Time Frame: 8 weeks after inclusion ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 18, 2011)

• Fatigue scores [ Time Frame: 8 and 30 weeks after inclusion ]
• Pain scores [ Time Frame: 8 and 30 weeks after inclusion ]
• Algometer testing response [ Time Frame: 8 and 30 weeks after inclusion ]
• Autonomic symptom scores [ Time Frame: 8 and 30 weeks after inclusion ]
• Quality of life-score [ Time Frame: 8 and 30 weeks after inclusion ]
• Disability scores [ Time Frame: 8 and 30 weeks after inclusion ]
• School attendance [ Time Frame: 8 and 30 weeks after inclusion ]
• Mean steps/day count during one week [ Time Frame: 30 weeks after inclusion ]
• Scores on cognitive function tests [ Time Frame: 8 and 30 weeks after inclusion ]
• The change in mean arterial pressure (MAP) during head-up tilt-test [ Time Frame: 8 and 30 weeks after inclusion ]
• The change in heart rate during head-up tilt-test [ Time Frame: 8 and 30 weeks after inclusion ]
• The change in LF/HF-ratio (a measure of autonomic control) during head-up tilt-test [ Time Frame: 8 and 30 weeks after inclusion ]
• Hormonal levels (inluding tryptophan metabolites) [ Time Frame: 8 and 30 weeks after inclusion ]
• Microbiological analyses [ Time Frame: 8 and 30 weeks after inclusion ]

Original Secondary Outcome Measures (submitted: December 28, 2009)

• Fatigue scores [ Time Frame: 8 and 30 weeks after inclusion ]
• Pain scores [ Time Frame: 8 and 30 weeks after inclusion ]
• Algometer testing response [ Time Frame: 8 and 30 weeks after inclusion ]
• Autonomic symptom scores [ Time Frame: 8 and 30 weeks after inclusion ]
• Quality of life-score [ Time Frame: 8 and 30 weeks after inclusion ]
• Disability scores [ Time Frame: 8 and 30 weeks after inclusion ]
• School attendance [ Time Frame: 8 and 30 weeks after inclusion ]
• Mean steps/day count during one week [ Time Frame: 30 weeks after inclusion ]
• Scores on cognitive function tests [ Time Frame: 8 and 30 weeks after inclusion ]
• The change in mean arterial pressure (MAP) during head-up tilt-test [ Time Frame: 8 and 30 weeks after inclusion ]
• The change in heart rate during head-up tilt-test [ Time Frame: 8 and 30 weeks after inclusion ]
• The change in LF/HF-ratio (a measure of autonomic control) during head-up tilt-test [ Time Frame: 8 and 30 weeks after inclusion ]
• Hormonal levels [ Time Frame: 8 and 30 weeks after inclusion ]
• Microbiological analyses [ Time Frame: 8 and 30 weeks after inclusion ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial
• Official Title: The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial

Brief Summary

The purpose of this study IS to

• explore the underlying pathophysiology of chronic fatigue syndrome (CFS) in adolescents, particularly focusing on genetics, infections/immunology, endocrinology, autonomic control and cognitions
• to assess the effect of clonidine (a drug that attenuates sympathetic nervous activity) in adolescent CFS.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Chronic Fatigue Syndrome
• Myalgic Encephalomyelitis

Intervention

• Drug: Clonidine

  Day 1-56 (week 1-8): 25 microgram (1 capsula) x 2/day for patients < 35 kg; 50 microgram (2 capsula) x 2/day for patients > 35 kg.

  Day 57-63 (week 9): 25 microgram (1 capsula) x 1/day for patients < 35 kg; 25 microgram (2 capsula) x 2/day for patients > 35 kg.

• Drug: Lactose capsula

  Day 1-56 (week 1-8): 1 capsula x 2/day for patients < 35 kg; 2 capsula x 2/day for patients > 35 kg.

  Day 57-63 (week 9): 1 capsula x 1/day for patients < 35 kg; 1 capsula x 2/day for patients > 35 kg

Study Arms

• Active Comparator: Clonidine capsula
  Intervention: Drug: Clonidine
• Placebo Comparator: Lactose capsula
  Intervention: Drug: Lactose capsula

Publications *

• Wyller VB, Eriksen HR, Malterud K. Can sustained arousal explain the Chronic Fatigue Syndrome? Behav Brain Funct. 2009 Feb 23;5:10. doi: 10.1186/1744-9081-5-10.
• Wyller VB, Due R, Saul JP, Amlie JP, Thaulow E. Usefulness of an abnormal cardiovascular response during low-grade head-up tilt-test for discriminating adolescents with chronic fatigue from healthy controls. Am J Cardiol. 2007 Apr 1;99(7):997-1001. Epub 2007 Feb 16.
• Asprusten TT, Sletner L, Wyller VBB. Are there subgroups of chronic fatigue syndrome? An exploratory cluster analysis of biological markers. J Transl Med. 2021 Jan 30;19(1):48. doi: 10.1186/s12967-021-02713-9.
• Wyller VB, Nguyen CB, Ludviksen JA, Mollnes TE. Transforming growth factor beta (TGF-β) in adolescent chronic fatigue syndrome. J Transl Med. 2017 Dec 4;15(1):245. doi: 10.1186/s12967-017-1350-1.
• Nguyen CB, Alsøe L, Lindvall JM, Sulheim D, Fagermoen E, Winger A, Kaarbø M, Nilsen H, Wyller VB. Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival. J Transl Med. 2017 May 11;15(1):102. doi: 10.1186/s12967-017-1201-0.
• Wyller VB, Vitelli V, Sulheim D, Fagermoen E, Winger A, Godang K, Bollerslev J. Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study. J Transl Med. 2016 May 5;14(1):121. doi: 10.1186/s12967-016-0873-1. Erratum in: J Transl Med. 2017 Jul 18;15(1):157.
• Fagermoen E, Sulheim D, Winger A, Andersen AM, Gjerstad J, Godang K, Rowe PC, Saul JP, Skovlund E, Wyller VB. Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial. BMC Pediatr. 2015 Sep 10;15:117. doi: 10.1186/s12887-015-0428-2.
• Winger A, Kvarstein G, Wyller VB, Sulheim D, Fagermoen E, Småstuen MC, Helseth S. Pain and pressure pain thresholds in adolescents with chronic fatigue syndrome and healthy controls: a cross-sectional study. BMJ Open. 2014 Oct 6;4(9):e005920. doi: 10.1136/bmjopen-2014-005920.
• Sulheim D, Fagermoen E, Winger A, Andersen AM, Godang K, Müller F, Rowe PC, Saul JP, Skovlund E, Øie MG, Wyller VB. Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial. JAMA Pediatr. 2014 Apr;168(4):351-60. doi: 10.1001/jamapediatrics.2013.4647.
• Fagermoen E, Sulheim D, Winger A, Andersen AM, Vethe NT, Saul JP, Thaulow E, Wyller VB. Clonidine in the treatment of adolescent chronic fatigue syndrome: a pilot study for the NorCAPITAL trial. BMC Res Notes. 2012 Aug 7;5:418. doi: 10.1186/1756-0500-5-418.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 28, 2009): 120
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 2012
• Actual Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Persisting or constantly relapsing fatigue lasting 3 months or more.
• Functional disability resulting from fatigue to a degree that prevent normal school attendance

Exclusion Criteria:

• Another disease process or current demanding life event that might explain the fatigue
• Another chronic disease (in particular pheochromocytoma, polyneuropathy, Renal insufficiency)
• Permanent use of pharmaceuticals (including hormone drugs)
• Permanently bed-ridden
• Positive pregnancy test
• Evidence of reduced cerebral and/or peripheral circulation due to vessel disease
• Know hypersensitivity towards clonidine or inert substances (lactose, sakkarose) in capsula
• Abnormal ECG (in particular bradyarrythmias due to sick sinus syndrome or AV-block. Isolated ectopic beats do not lead to exclusion)
• Supine heart rate < 50 beats/min
• Supine systolic blood pressure < 85 mmHg
• Systolic blood pressure fall upon standing > 30 mmHg

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Norway

Administrative Information

• NCT Number: NCT01040429
• Other Study ID Numbers: NorCAPITAL.02
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Vegard Bruun Wyller, Oslo University Hospital
• Study Sponsor: Oslo University Hospital
• Collaborators: Not Provided

Investigators

• Principal Investigator: Vegard Bruun Wyller, MD, PhD; Dept. of Pediatrics, Oslo University Hospital, Norway

• PRS Account: Oslo University Hospital
• Verification Date: November 2012