Therapy with the Cytokine Modulator COBAT is Associated with Decreased Fatigue in Patients with Chronic Fatigue
Mayerson, S.E.; Taub, F.E.
Background
Administration of cytokines, including IFN-alpha and IL-2, is associated with "cytokine syndrome" whose symptoms are similar to those often reported by patients with Chronic Fatigue Syndrome (CFS) and/or fibromyalgia. Carbobenzyoxy beta-alanyl taurine (COBAT) has been reported to modulate expression of a number of cytokines when applied to human PBMCs in culture (Dunn, et al). The initial signaling event appears to be an alteration in Ca flux, which is seen at doses of 10 nM or greater. Initial placebo-controlled double-blind studies of administration of low doses of COBAT suggested it had physiologic effects (p=0.001) with no significant toxicity.
Objective
In order to assess potential utility in CFS and other causes of fatigue, a multi-center outpatient clinical outcome study of COBAT in persons with fatigue was performed.
Methods
Following approval of the Southern California University of Health Sciences' Institutional Review Board (IRB), studies were initiated. Twelve items from the FACIT-Fatigue scale (which uses a Likert-type scale, 0-48 total points) were used to measure fatigue. Nineteen patients with CFS and fatigue due to other causes (including HCV and cancer) were followed. Major events (such as initiation of chemotherapy) expected to alter fatigue levels were cause for termination of the study for that patient.
Results
No drug related adverse events (AEs) or serious AEs (SAEs) were reported. No clear patterns were seen in patients with low fatigue scores consistent with normal physiologic tiredness. However, in patients with pre-study scores of 24 or greater, there was a pattern of decreased fatigue that was progressive for at least 4-6 weeks. Typically it began one or more weeks following initiation of therapy. Over 90% of patients reported decreased fatigue. Comparison of pre-study and on-study fatigue levels revealed statistically significant reduction (p=0.0001). The median decrease in the total fatigue score was 53%. (The average score pre-study was 33 versus an average post-study score of 17 following 4 or more weeks of study). Similar effects were seen at all clinical sites and in patients with various causes of fatigue, including CFS, cancer and HCV.
Conclusion
A highly significant reduction in fatigue was associated with COBAT therapy. The relative contribution of the placebo effect and the drug to the decrease in fatigue was not examined by the design used. However, the experiment strategy and data does strongly support the conclusion that administering COBAT to patients with moderate to severe fatigue will result in them experiencing a significant relief of symptoms without significant side effects.
ACKNOWLEDGEMENT: The participating clinicians (in alphabetical order) included: Toni Bark, M.D.; Zidi Berger, M.D., N.D.; Mitchell Fleisher, M.D.; Terri I. Gilbert, N.D.; Tedde M. Rinker, M.D.; and David Servan-Schreiber, M.D. The authors, who simply compiled the data, gratefully acknowledge their efforts.