Tumor Necrosis Factor-alpha Inhibition Using Etanercept in Chronic Fatigue Syndrome

Tumor Necrosis Factor-alpha Inhibition Using Etanercept in Moderate and Serious Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME), Including in Patients With no Clinical Response After B-lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab.

The hypothesis is that a subset of patients with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME), including also patients with no clinical response after B-cell depletion therapy using the anti-CD20 antibody Rituximab, may benefit from tumor necrosis factor-alpha inhibition using Etanercept as weekly subcutaneous injections.

Study Overview

• Status: Terminated
• Conditions: Chronic Fatigue Syndrome; Myalgic Encephalomyelitis
• Intervention / Treatment: Drug: Etanercept

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway, N-5021
    • Dept. of Oncology and Medical Physics, Haukeland University Hospital Bergen, Norway

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 62 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME)
• moderate and serious CFS/ME severity
• age 18-66 years
• informed consent

Exclusion Criteria:

• patients with fatigue, not fulfilling criteria for CFS
• pregnancy or lactation
• previous malignant disease, except basal cell carcinoma of skin and cervical carcinoma in situ
• previous long-term systemic treatment with immunosuppressive drugs such as cyclosporine, azathioprin, mycophenolate mofetil, except steroids e.g. in obstructive lunge disease.
• demyelinating disease, such as multiple sclerosis.
• heart failure.
• endogenous depression.
• lack of ability to comply to the protocol.
• multi-allergy with risk of serious drug reaction
• reduced renal function (creatinine > 1.5 x UNL)
• reduced liver function (bilirubin or transaminases > 1.5 x UNL)
• HIV positivity. Evidence of clinically significant infection. Previous viral hepatitis with risk of reactivation. High risk of opportunistic infections. Latent tuberculosis must be treated before inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etanercept	Drug: Etanercept; Weekly subcutaneous injections of Etanercept 50 mg, for up to 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom alleviation within 12 months follow-up, as compared to baseline, measured by standardized self-reports and quality of life schemes.	The primary endpoint is defined as moderate or major response of the CFS/ME symptoms, of at least six weeks duration, independent on when during 12 months follow-up the response period(s) occurs. Single such response periods, and the sum of these, are recorded.	Response of at least six weeks duration, independent on when occuring, during 12 months follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom alleviation, as compared to baseline, measured by standardized self-reports and quality of life schemes.	The secondary outcome measures are effect on the CFS/ME symptoms, by evaluation at 3, 6, 9, 12 months after start of intervention.	At 3, 6, 9, 12 months after start of intervention.

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Investigators: Principal Investigator: Øystein Fluge, MD, PhD, Dept. of Oncology and Medical Physics, Haukeland University Hospital

Publications and helpful links

General Publications

• Fluge O, Bruland O, Risa K, Storstein A, Kristoffersen EK, Sapkota D, Naess H, Dahl O, Nyland H, Mella O. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study. PLoS One. 2011;6(10):e26358. doi: 10.1371/journal.pone.0026358. Epub 2011 Oct 19.
• Fluge O, Mella O. Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series. BMC Neurol. 2009 Jul 1;9:28. doi: 10.1186/1471-2377-9-28.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: November 8, 2012
• First Submitted That Met QC Criteria: November 15, 2012
• First Posted (Estimate): November 21, 2012

Study Record Updates

• Last Update Posted (Estimate): December 2, 2015
• Last Update Submitted That Met QC Criteria: November 30, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: CFS; TNF-alpha; Etanercept; Myalgic Encephalomyelitis (ME); Chronic fatigue syndrome; CFS/ME; Tumor necrosis factor-alpha
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Infections; Pain; Neurologic Manifestations; Disease; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Musculoskeletal Pain; Central Nervous System Infections; Syndrome; Fatigue; Myalgia; Necrosis; Fatigue Syndrome, Chronic; Encephalomyelitis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: 2011/2500; 2011-006069-16 (EudraCT Number)