CycloME is a clinical trial sponsored by the ME/CFS research group at the Department of Oncology and Medical Physics at Haukeland University Hospital, Bergen, Norway. Senior Consultant Øystein Fluge and Professor Olav Mella are the study supervisors. Kari Sørland, a nurse, is the national project coordinator. The Kavli Trust, a humanitarian foundation, is contributing to the trial by funding 50 percent of a nursing post for 12 months.
Cyclophosphamide[edit | edit source]
Cyclophosphamide, a chemotherapy and immunosuppressant drug, is being investigated as a treatment in ME/CFS. As with the rituximab studies, the potential efficacy with ME was stumbled on by accident after treating two breast cancer patients, who also had ME, with cyclophosphamide, and having the women report that their ME symptoms improved. Before treatment, a bedbound ME patient walked an average of 326 steps per day. After six infusions with cyclophosphamide, she was able to walk 13,000 steps daily.
CycloME part A[edit | edit source]
The cyclophosphamide trial is a single centre, unblinded study with 40 patients with moderate to severe ME. All study participants have been chosen and treatments have started. Some of the participants are either non-responders when they were treated with Rituximab or were patients who relapsed after treatment with Rituximab. The Department of Oncology at Haukeland University Hospital is responsible for assessing which patients to include the trial, as well as administering the treatments. The Norwegian Radium Hospital, Oslo, is taking part in the trial as a treatment centre, administering treatments to a small group of patients who reside in the Oslo area. The Canadian Consensus Criteria was used in selecting participants.
All participants will receive six intravenous treatments of cyclophosphamide, each treatment four weeks apart. The participants will be followed-up for one year. Each will be given complete physical examinations and testing before and after treatment, and each will submit regular reports on any changes in symptoms and physical function. The physical function testing will include a measurement of activity via a Sensewear armband (a wearable device that measures physical activity and total energy expenditure expressed as Kcalories), a two-day Cardiopulmonary exercise tests for those who are able, and self-reporting fatigue scores. Adverse effects will be tested for with physical examinations and laboratory tests. Side effects are expected to be minimal, because similar dosages have already been used in breast cancer and lymphoma trials.
The last participant will complete treatment in June 2016. Study results will be published in 2017. Data analysis with include comparing the group who received rituximab prior to those who did not.
CycloME part B[edit | edit source]
The Haukeland University Hospital ME/CFS research group is prepared that if the interim results from CycloME part A show a positive improvement in symptoms in a minimum of 40% of the patients, the trial may be extended to include patients with very severe ME. In part B, both treatment and follow-up will be completed in collaboration with the patient’s local primary health service.
If the results from CycloME part A are negative, or fewer than 40% of the participants have a positive response, part B will not be implemented. An investigator meeting planned in September 2016 will look at preliminary data for the efficacy, as well as any toxicity of part A of the study, and assess the feasibility of continuing on with CycloME part B.
In October, 2016, it was reported that approval for CycloME part B was granted.
Study Outcome Measures[edit | edit source]
Primary Outcome Measures:
- Self reported fatigue score, and
- overall response as the effect of treatment on ME/CFS symptoms, both measure within a 12 months follow-up period.
Secondary Outcome Measures:
- Short Form-36 (SF-36), recorded at baseline, and at 3, 6, 9 and 12 months follow-up,
- Physical activity via a Sensewear armband, recorded at baseline, at 7-9 months, and at 11-12 months, *Cardiopulmonary exercise tests for two following days, performed at baseline, and repeated at 7-9 months, and 11-12 months,
- Self-recorded Function level, recorded at baseline, and at 3, 6, 9 and 12 months follow-up,
- Fatigue Severity Scale (FSS), completed at baseline, 3, 6, 9 and 12 months,
- Longest duration of continuous response duration, measured by a self-reported fatigue score ≥ 4,5 (for at least 6 consecutive weeks) within 12 months follow-up,
- Sustained clinical response at 12 months, defined as a fatigue score of at least 4.5 at 12 months follow-up, and
- Safety and tolerability, including adverse events, measured by patient history, physical exam, and lab tests, performed every four weeks the first six months, thereafter at 6, 9 and 12 months follow-up. Adverse events may include include hair loss, vomiting, diarrhea, jaundice, leukopenia, anemia, thrombocytopenia, infections, allergic reactions and hemorrhagic cystitis, disturbed ovarian function. Information collection on possible toxicity will continue after the formal 12 months study period.
Learn more[edit | edit source]
- 20 Oct 2016, The RituxME and CycloME studies – Ongoing Clinical Research in the ME/CFS Research Group
- CycloME website
- ClinicalTrial.gov page for CycloME study
See also[edit | edit source]
References[edit | edit source]
Myalgic encephalomyelitis (ME) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.
Adverse reaction - Any unintended or unwanted response to the treatment under investigation in a clinical trial.