This trial is active, not recruiting.

Conditions chronic fatigue syndrome (cfs), myalgic encephalomyelitis (me)
Treatment cyclophosphamide
Phase phase 2
Sponsor Haukeland University Hospital
Collaborator The Kavli Foundation
Start date March 2015
End date January 2017
Trial size 40 participants
Trial identifier NCT02444091, 2014-004029-41, KTS-7-2015


Significant clinical improvements of ME/CFS symptoms were observed in two patients with long-standing ME/CFS who received adjuvant chemotherapy including cyclophosphamide for breast cancer, also in one ME/CFS patient who received chemotherapy including iphosphamide for Hodgkin lymphoma.

Three pilot ME/CFS patients were thereafter treated with six intravenous infusions four weeks apart, in two of these with a significant clinical response.

The hypothesis is that a subset of ME/CFS patients have an activated immune system, and that ME/CFS symptoms may be alleviated by treatment with cyclophosphamide as intravenous pulse infusions four weeks apart, six infusions in total.

The purpose of the present study is to treat ME/CFS patients with cyclophosphamide as intravenous pulse infusions four weeks apart, six infusions in total. The effects on ME/CFS symptoms and tolerability/side effects during 12 months follow-up will be registered, and additional tests will be performed to objectively register changes in physical ability during follow-up. Studies to investigate possible large vessel endothelial dysfunction and skin microvascular dysfunction will be performed before start of intervention and during follow-up.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Cyclophosphamide, intravenous infusions four weeks apart. Six infusions in total. First infusion: 600 mg/m2. Infusions 2 to 6: 700 mg/m2
Cyclophosphamide intravenous infusions four weeks apart, in total six infusions. First infusion: cyclophosphamide 600mg/m2. Infusions 2 to 6: cyclophosphamide 700 mg/m2 . Follow-up for 12 months.

Primary Outcomes

Fatigue score, selfreported
time frame: Within 12 months follow-up
Overall response
time frame: Within 12 months follow-up

Secondary Outcomes

Short Form-36 (SF-36)
time frame: Recorded at baseline, and at 3, 6, 9 and 12 months follow-up.
Physical activity (Sensewear armband)
time frame: Recorded at baseline, at 7-9 months, and at 11-12 months
Cardiopulmonary exercise tests for two following days
time frame: At baseline, and repeated at 7-9 months, and 11-12 months
Self-recorded Function level
time frame: At baseline, and at 3, 6, 9 and 12 months follow-up
Fatigue Severity Scale
time frame: Baseline, 3, 6, 9 and 12 months
Longest continuous response duration
time frame: Within 12 months follow-up
Sustained clinical response at 12 months
time frame: Assessment at end of follow-up (12 months)
Safety and tolerability
time frame: Continuously within the study period of 12 months

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria: - Patients with ME/CFS according to "Canadian" criteria (2003) - Duration of ME/CFS at least 2 years - Mild/Moderate, Moderate, Moderate/Severe and Severe ME/CFS may be included - Age 18-65 years - Signed informed consent Exclusion Criteria: - Patients with fatigue who do not comply by the diagnostic "Canadian" criteria (2003) for ME/CFS - Duration of ME/CFS less than 2 years - Mild ME/CFS - Very severe ME/CFS (bedridden requiring help for all tasks) - Patients where the workup uncovers other pathology as possible cause of symptoms - Pregnancy or breast feeding - Previous malignant disease (except basal cell carcinoma of skin and cervical carcinoma in situ/dysplasia) - Previous long-term systemic treatment with immunosuppressive agents (e.g. azathioprine, ciclosporin, mycophenolate mofetil). Except steroid treatment for e.g. obstructive lung disease or autoimmune diseases such as e.g. ulcerative colitis - Serious endogenous depression - Lack of ability to complete the study including follow-up - Reduced renal function (creatinine > 1.5 x UNL) - Reduced liver function (bilirubin or transaminases > 1.5 x UNL) - Known hypersensitivity to cyclophosphamide or metabolites - Reduced bone marrow function - Ongoing cystitis or urinary tract obstruction - Known HIV positivity, previous hepatitis B or hepatitis C, or reason to suspect other ongoing and clinically relevant infection

Additional Information

Official title Cyclophosphamide in Myalgic Encephalopathy/ Chronic Fatigue Syndrome (ME/CFS). Part A: an Open Label Phase-II Study With Six Intravenous Cyclophosphamide Infusions Four Weeks Apart, and Follow-up for 12 Months
Principal investigator Mella Olav, MD, PhD
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Haukeland University Hospital.