Clinical trials

Barry Hurwitz, a colleague of Dr. Nancy Klimas at the University of Miami, presented the findings of their famous "ProCrit Study." 57 PWCs were studied for anemia and low red blood cell volume (RBCV). About 70% of the cohort actually had a low RBC volume. These were given either ProCrit (n=30) or placebo (n=10), while those with normal RBC volume were given placebo injections for 4 months. All were administered iron and dietary salt supplements also. 80% of treated subjects responded to 10,000 units per week of ProCrit, and their RBC volume increased about 26% on average. Orthostatic intolerance (by tilt table testing) improved in treated subjects, but exercise tolerance, fatigue, and other measures did not change. Thus, ProCrit therapy might be modestly helpful for patients with orthostatic intolerance and low RBCV, but not for the general symptoms of CFS/ME.

José Montoya (Stanford University School of Medicine) described his recent valgancyclovir (Valcyte^TM) studies in 12 persons with virally-induced fatigue and cognitive dysfunction. Subjects were treated with valgancyclovir for 6 months (one for 3 months only), and 9 had significant improvement in fatigue and cognition. Five of these had elevated EBV titers (VCA-IgG, EBNA, or EBV-EA), 3 had both elevated EBV and HHV-6 serologies, one had neither. None had HHV-6 elevations alone.

Comment: It is not at all clear if any of these patients had CFS/ME. We can only say that a subset of persons with Post-Infectious Viral Syndrome may respond to prolonged therapy with valgancyclovir. Dr. Montoya warned that valgancyclovir is a dangerous drug and must be used with great caution. A study of valgancyclovir specifically in persons with CFS/ME is slated to start this month, and we all anxiously await the outcome!

Martin Lerner (Wayne State University, Detroit) described a subset of patients with persistent EBV and/or cytomegalovirus (CMV), electrocardiographic changes, and symptoms of CFS/ME. In addition to having elevated IgM (or EBV-EA) titers, all 37 patients had an elevated heart rate at rest, recurrent T-wave inversions on Holter monitoring, cardiac abnormalities and/or biopsy proven cardiomyopathy. Subjects with EBV positivity were treated with high dose valcyclovir (VCV or Valtrex^TM) 14mg/kg daily, and subjects with CMV positivity were treated with valgancyclovir (VGCV or Valcyte^TM) for 3 to 3.5 years with improvement in fatigue, tachycardia, chest pain, syncope, flu-like symptoms, EBV titers, and cardiac wall motion. No serious adverse effects were seen.

Pain

Dan Clauw (University of Michigan, Ann Arbor) provided his usual elegant and fascinating presentation, this time on "Pain Processing and Therapy in Fibromyalgia." Clauw explained that each of us has a "volume control" for controlling the severity of pain, and that this controller is affected by both genetics and environment (or experience). Studies have shown that persons with FM (PWFs) have a normal "detection threshold" for pain, but a decreased "noxious threshold" to a variety of stimuli, including pressure, heat, noise, and electrical stimulation. Thus, PWFs sense the onset of pain the same as other individuals, but are much more sensitive to pain. This is independent of expectancy or hypervigilance.

Such findings can be demonstrated by a functional MRI scan ( fMRI), which senses deoxygenated blood and thereby detects parts of the brain that are activated. Using this technique, Clauw's group has demonstrated that healthy individuals have a minimal response to a modest pain stimulus, while PWFs have a very strong response to the same modest stimulus. This proves, Clauw explains, that "when FM patients say they hurt, they really do hurt!"

Studies have also shown that pain is unrelated to co-morbid depression, but persons who catastrophize (negative thoughts, magnification of symptoms, "glass-half-empty") tend to experience more pain.

Clauw's management of pain parallels The Stepwise Approach espoused at the Hunter-Hopkins Center: education, pharmacologic therapy, aerobic exercise, alternative therapies (such as hypnotherapy, biofeedback, acupuncture, chiropracty, electrostimulation) and Cognitive Behavioral Therapy (or coaching). He reports good evidence that the following are helpful:

• Tricyclic antidepressants (amitriptyline, cyclobenzaprine)
• SNRIs (venlafaxine, duloxetine) and possibly SSRIs
• Tramadol.

There is weak evidence for using growth hormone, 5-hydroxy-tryptane, tropisetron, and SAMe; and NO evidence supports the use of NSAIDs (ibuprofen, naproxen, etc.), corticosteroids, or guaifenesin. Clauw is not a fan of opioids, narcotics, or sleep medications in the treatment of FM. Newer possible therapies for fibropain include GHB (Xyrem^TM), dopamine agonists (roprinolole, pramipexole), and neuromodulators.

Lastly, Clauw pointed out that there is a strong familial predisposition to fibromyalgia, with first degree relatives having 8 times the risk of developing FM. Also, Diatchenko has linked abnormalities in the COMT haplotype (which controls serotonin in the body and brain) to TMJ. This means that at least one gene codes for pain, and possibly the tendency to develop FM.