Cytokine Inhibition in Chronic Fatigue Syndrome Patients
Condition: Chronic Fatigue Syndrome
MeSH terms: Fatigue Syndrome, Chronic; Syndrome; Fatigue
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Rationale: 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. Although
      derangements of the cytokine network in CFS are controversial, a major problem is that many
      studies did not use adequate controls. In addition, all studies have been performed on
      peripheral venous blood of the patients. As cytokines mainly act in the tissues, e.g., the
      brain, the information that can be derived from peripheral blood cells is limited. The only
      information regarding the possible role of cytokines in the pathophysiology of CFS could come
      from intervention studies in which pathogenetically important cytokines are inhibited. A
      potentially relevant cytokine which can be blocked in humans without severe side effects is
      IL-1. Although it is plausible that these cytokines play a role in CFS, there is limited
      evidence for this.

      Objective: To investigate the effect on symptomatology of interference with IL-1 in CFS
      patients.

      Study design: A randomized placebo controlled study will be performed to determine whether
      interference with IL-1 is able to reduce fatigue and disabilities in CFS patients.

      Study population: Female CFS patients without psychiatric co-morbidity will be included in
      this study. Patients of the outpatient clinic of the Department of General internal medicine
      and the Expert Centre for Chronic Fatigue (ECCF) will be asked to participate in the study.
      Patients will be asked to bring a healthy neighbourhood control to their first study visit.

      Intervention: After inclusion patients will be randomized to receive one of the following
      treatments:

        -  interleukin-1 inhibitor Anakinra (IL-1Ra) for 4 weeks (N=25);

        -  placebo for 4 weeks (N=25).

      Main study parameters/endpoints: The primary outcome measure will be fatigue severity
      measured with the Checklist Individual Strength (CIS) at 4 weeks, measurement will be
      repeated up to 26 weeks.

      Secondary outcome measures will be:

        -  level of functional impairment measured with the Sickness Impact Profile (SIP8) total
           score;

        -  physical and social functioning assessed with the subscale physical functioning and
           social functioning of the SF-36;

        -  level of psychological distress assessed with the total score on the Symptom
           Checklist-90 (SCL-90);

        -  pain severity assessed with a Visual Analog Scale (VAS);

        -  cytokine measurement in blood (plasma and blood in Pax-gene tubes) and saliva (at
           protein and mRNA level);

        -  cortisol measurement in saliva and hair;

        -  microbiome determination in faeces;

        -  body temperature and pulse rate.
    


Intervention name(s): Anakinra; Placebo
Intervention type(s): Drug; Drug
Other intervention name(s): Kineret
Intervention MeSH terms: Interleukin 1 Receptor Antagonist Protein
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Chronic fatigue syndrome; Cytokines; Interleukin-1; Fatigue; Anakinra