Cyclophosphamide in Myalgic Encephalopathy/ Chronic Fatigue Syndrome (ME/CFS)

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

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.

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