Our hypothesis is that chronic fatigue syndrome is an autoimmune disease, often triggered by infections. After treatment with Rituximab, patients experience fast B-cell depletion, yet it takes 2-8 months before the signs of clinical response to ME symptoms. The time course of response, delayed in relation to the B-cell reduction is best compatible with the gradual elimination of autoantibodies from the plasma. For the poorest group of patients in KTS-3-2010 with significantly reduced functional level, we believe it may take a long time (up to one year) before they see responses after Rituximab treatment alone, if there is a correlation between the level of presumptive autoantibodies and disease severity. It causes a strain for patients to travel to hospital (or from elsewhere in the country) for treatment every three months. Based on the hypothesis of disease-specific autoantibodies, it is a logical to try plasma exchange as initial therapy for this group, followed by Rituximab treatment as outlined in the minutes of KTS-3-2010. The hypothesis is that a faster removal of autoantibodies by a series of plasma replacements (in this case five treatments) followed by an immunosuppressive maintenance therapy, may result in a faster clinical response such as is known in certain immunological disorders with varying systemic manifestations (such as Wegener's granulomatosis , Goodpasture's syndrome, Guillain Barré). We therefore wish to apply for amendment to the study KTS-3-2010, as we want to expand the study to 5 patients, and 3-5 of the poorest patients in the study treated with initial plasma exchange (by Division of Kidney Diseases, Department of Medicine, Haukeland University) followed by B-cell depletion, as outlined in the protocol for the study. Objectives of the amendment (addition) to the Protocol is to shorten the interval from study entry to the response experienced by patients, as well as evaluating tolerance for this procedure in severely ill ME patients. It will also help to shed light on disease mechanisms in severe chronic fatigue syndrome. For 3-5 patients in the study KTS-3-2010, with very severe chronic fatigue syndrome. We will conduct initial standard plasma exchange with albumin-Ringer solution (one plasma volume, up to 5 treatments) by temporary dialysis catheter in the groin or internal jugular vein, the 1-2 weeks. 3 weeks after plasma exchange initiation of B-cell depletion as indicated in the protocol for KTS-3-2010: Rituximab 500 mg/m2 (1000 mg) twice two weeks apart, followed by maintenance therapy with Rituximab (500 mg/m2 , max 1000 mg) after 3, 6, 10 and 15 months. Otherwise identical to the protocol for KTS-3-2010 as it is stated in the previous application.
For patients who have plasma exchange before initiation of rituximab treatment:
This appendix describes plasma exchange we will give you at the start, three weeks before starting treatment with Rituximab as outlined in the general patient information for the study. Our theory is that chronic fatigue syndrome is a so-called autoimmune diseases, and that the autoantibodies in the plasma produced from cells based on B-lymphocytes, that is, antibodies that react against the body itself, instead of reacting to foreign substances in the environment. When a patient is treated with rituximab it depletes B cells rapidly but autoantibodies already present degrade slowly. For the most severely ill ME patients, it is possible that the amount of such autoantibodies in plasma is very high, and it may take a long time before patients achieve an improvement of symptoms by Rituximab treatment alone. It may be difficult for very sick ME patients having to wait up to one year of recovery, with several trips to the hospital for Rituximab infusions. We therefore believe it would be beneficial with plasma exchange before initiation of rituximab treatment aiming to rapidly reduce the amount of autoantibody so the patient can get improvement in symptoms earlier. Plasma replacement is an established procedure that takes place at the Renal Section, Department of Medicine, Haukeland University Hospital, under the leadership of Chief Einar Svarstad. The department has broad expertise and extensive experience with such a procedure from other diseases, including other autoimmune diseases where there is a need for rapid reduction of pathogenic autoantibody from the patient's blood (plasma). Before the procedure must be inserted a catheter into a vein either on the neck or groin, this is done with local anesthesia. During the procedure given a small dose of blood-thinning medication (heparin). The treatment usually takes about 2-3 hours each time, and usually repeated five times in one week. During the procedure carried blood through a filter that separates blood cells from blood plasma. Plasma containing the pathogenic autoantibodies removed and replaced with egg white solution (albumin), salts and water. Side effects you may experience during plasma exchange may be anxiety, nausea and dizziness. Serious complications are seen very rarely.
