Cytokine inhibition in chronic fatigue syndrome patients: study protocol for a randomized controlled trial

• Published in: Current controlled trials in cardiovascular medicine Vol. 16; no. 1; p. 439
• Main Authors: Roerink, Megan E, Knoop, Hans, Bredie, Sebastian J H, Heijnen, Michael, Joosten, Leo A B, Netea, Mihai G, Dinarello, Charles A, van der Meer, Jos W M
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05.10.2015; BioMed Central
• Subjects: Adolescent; Adult; Behavior therapy; Behavioral health care; Care and treatment; Cerebrospinal fluid; Checklist; Chronic fatigue syndrome; Clinical Protocols; Clinical trials; Cognitive therapy; Comorbidity; Cytokines; Development and progression; Disability; Disability Evaluation; Double-Blind Method; Evidence-based medicine; Exercise therapy; Fatigue Syndrome, Chronic - diagnosis; Fatigue Syndrome, Chronic - drug therapy; Fatigue Syndrome, Chronic - immunology; Fatigue Syndrome, Chronic - physiopathology; Fatigue Syndrome, Chronic - psychology; Female; Females; Good Manufacturing Practice; Health aspects; Health Status; Humans; Hydrocortisone - blood; Immunologic Factors - adverse effects; Immunologic Factors - therapeutic use; Influenza; Interleukin 1 Receptor Antagonist Protein - adverse effects; Interleukin 1 Receptor Antagonist Protein - therapeutic use; Interleukin-1 - antagonists & inhibitors; Interleukin-1 - immunology; Interleukins; Internal medicine; Medical law; Medical research; Medicine, Experimental; Mental Health; Middle Aged; Muscle pain; Muscle Strength; Netherlands; Pain Measurement; Participation; Pathophysiology; Patient outcomes; Pharmacists; Pharmacology; Research Design; Severity of Illness Index; Signal Transduction - drug effects; Study Protocol; Surveys and Questionnaires; Time Factors; Treatment Outcome; Tumor necrosis factor-TNF; Young Adult; Netherlands
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-015-0971-z

Chronic fatigue syndrome (CFS) is a medically unexplained syndrome for which no somatic or pharmacological treatment has been proven effective. Dysfunction of the cytokine network has been suspected to play a role in the pathophysiology of CFS. The disturbances of the cytokine network detected in CFS patients are highly variable, in part due to the lack of adequate controls in many studies. Furthermore, all studies have been performed on peripheral venous blood of patients. As cytokines mainly act in tissues, for example, the brain, the information that can be derived from peripheral blood cells is limited. The information regarding the possible role of cytokines in the pathophysiology could come from intervention studies in which the activities of relevant cytokines are reduced, for example, reducing interleukin-1, interleukin-6 or tumor necrosis factor. In this study, the clinical usefulness of anakinra, an IL-1 antagonist, will be assessed in patients with CFS. A randomized placebo-controlled, double-blind trial will be conducted. Fifty adult female patients meeting the Centers for Disease Control (CDC) criteria for CFS and without psychiatric co-morbidity will be included. After inclusion, patients will be randomized between treatment with anakinra (recombinant human interleukin-1 receptor antagonist) or placebo. Each group will be treated for 4 weeks. Outcome measures will be assessed at baseline, after 4 weeks of intervention, and 6 months after baseline assessment. The primary outcome measure will be fatigue severity at 4 weeks, measured with the validated Checklist of Individual Strength (CIS). Secondary outcome measures are functional impairment, physical and social functioning, psychological distress, pain severity, presence of accompanying symptoms, and cytokine and cortisol concentrations. This is the first randomized placebo-controlled trial that will evaluate the effect of interference with IL-1 on the experience of fatigue in patients with CFS. The results of this study may expand treatment options for patients with CFS, for whom graded exercise therapy and cognitive behavioral therapy are the only evidence-based interventions that exist at this moment. Clinicaltrials.gov: NCT02108210 . Clinicaltrials.gov registration date: 8 April 2014. EudraCT: 2013-005466-19.