Trial record 9 of 31 for:    Open Studies | "Fatigue Syndrome, Chronic"

Cytokine Inhibition in Chronic Fatigue Syndrome Patients (CiCFS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Radboud University
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT02108210
First received: March 21, 2014
Last updated: July 4, 2014
Last verified: July 2014
  Purpose

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.

Condition Intervention Phase
Chronic Fatigue Syndrome
Drug: Anakinra
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cytokine Inhibition in Chronic Fatigue Syndrome Patients - a Pilot Study

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • CIS (checklist individual strength, compared to baseline) [ Time Frame: 4 weeks, measurement will be repeated up to 26 weeks ] [ Designated as safety issue: No ]
    To investigate the role of the cytokine IL-1 in the pathogenesis of CFS and to find leads for future treatment of CFS, a disorder for which there is no proven effective drug treatment. The primary outcome measure will be fatigue severity at 4 weeks measured with the Checklist Individual Strength (CIS).


Secondary Outcome Measures:
  • SIP8 (sickness impact profile, change from baseline) [ Time Frame: 4 weeks, measurement will be repeated up to 26 weeks ] [ Designated as safety issue: No ]
    level of functional impairment

  • SF-36 (subscale physical functioning and social functioning, compared to baseline) [ Time Frame: 4 weeks, measurement will be repeated up to 26 weeks ] [ Designated as safety issue: No ]
    physical and social functioning assessed with the subscale physical functioning and social functioning of the SF-36

  • SCL-90 (symptom checklist-90, compared to baseline) [ Time Frame: 4 weeks, measurement will be repeated up to 26 weeks ] [ Designated as safety issue: No ]
    level of psychological distress assessed with the total score on the Symptom Checklist-90

  • VAS pain (visual analog scale, compared to baseline) [ Time Frame: 4 weeks, measurement will be repeated up to 26 weeks ] [ Designated as safety issue: No ]
    pain severity assessed with a Visual Analog Scale

  • Cortisol in saliva and hair (concentration compared to baseline) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Because of the possible role of the hypothalamus-pituitary-adrenal axis we will also measure the cortisol concentration in saliva and hair. For the baseline assessment, comparison will be made with matched neighbourhood controls.

  • microbiome determination faeces [ Time Frame: at baseline ] [ Designated as safety issue: No ]
    A new field of great interest in pathophysiology is the role of the microbial flora of the host (microbiome). The availability of well defined patients with CFS and matched controls is a great opportunity in an unexplored area of CFS research, to assess whether the microbiome of CFS patients is peculiar.

  • cytokine concentrations in blood and saliva (compared to baseline) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    In addition to the cytokine intervention, we will assess cytokines (at the transcriptional level and as proteins) in serum and saliva at baseline and after 4 weeks of intervention. For the baseline assessment, comparison will be made with matched neighbourhood controls.


Other Outcome Measures:
  • Body temperature [ Time Frame: 4 weeks, measurement will be repeated up to 26 weeks ] [ Designated as safety issue: No ]
  • pulse rate [ Time Frame: 4 weeks, measurement will be repeated up to 26 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: June 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anakinra
This therapy will consist of once daily subcutaneous injections (100mg/day) during a period of 4 weeks. Patients will be monitored at week 1 and week 4 after starting medication for development of side effects. Therapy will be stopped in case of severe side effects, interfering disease or pregnancy.
Drug: Anakinra
Other Name: Kineret
Placebo Comparator: Placebo
Patients in the placebo group will also receive once daily subcutaneous injection during a period of 4 weeks. Placebo injections will be identically in appearance compared to the Anakinra injections. Patients in the placebo group will have the same visits and monitoring for side effects as the patients randomized to the other treatment arm.
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 59 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • CDC-diagnosed CFS-patients;
  • female, between 18 and 59 years old;
  • fatigue duration ≤10 years, or significant increase of complaints during the last 10 years
  • score of ≥40 on the subscale fatigue severity of the CIS (Checklist Individual Strength);
  • marked functional impairment assessed with the Sickness Impact Profile (SIP-8) and operationalised as a total score of ≥700.

Exclusion Criteria:

  • pregnant or nursing women;
  • women who intend to get pregnant during the study;
  • fatigue duration >10 years;
  • patients who use or have used psychotropic medication in the past month;
  • substance abuse in the past 3 months;
  • patients taking any medication except oral contraceptives and/or paracetamol;
  • patients with evident somatic co-morbidity;
  • previous or current engagement in CFS research;
  • inability to understand the nature and the extent of the trial and the procedure required;
  • psychiatric co-morbidity (major depression, psychosis, eating disorders, anxiety disorders, bipolar disease and post traumatic stress disorder) assessed with the MINI;
  • live vaccination during the past four weeks;
  • current engagement in a legal procedure with respect to disability claims.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02108210

Contacts
Contact: Megan Roerink, MD 0628878681 Megan.Roerink@radboudumc.nl
Contact: Jos van der Meer, Prof, PhD, MD Jos.vanderMeer@radboudumc.nl

Locations
Netherlands
RadboudUMC Recruiting
Nijmegen, Gelderland, Netherlands, 6500HB
Contact: Megan Roerink, MD    0628878681    Megan.Roerink@radboudumc.nl   
Sub-Investigator: Megan E Roerink, MD         
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Jos van der Meer, Prof, PhD, MD Radboudumc
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT02108210     History of Changes
Other Study ID Numbers: R0002198, 2013-005466-19, NL47571.091.14
Study First Received: March 21, 2014
Last Updated: July 4, 2014
Health Authority: Netherlands: CMO Arnhem Nijmegen

Keywords provided by Radboud University:
Chronic fatigue syndrome
Cytokines
Interleukin-1
Fatigue
Anakinra

Additional relevant MeSH terms:
Fatigue Syndrome, Chronic
Fatigue
Signs and Symptoms
Virus Diseases
Muscular Diseases
Musculoskeletal Diseases
Encephalomyelitis
Central Nervous System Diseases
Nervous System Diseases
Neuromuscular Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014