Although fludrocortisone didn't help the patients in this study, other drugs or drug combinations, including certain heart medications, may still benefit them and need to be formally tested, say the authors from the National Institute of Allergy and Infectious Diseases (NIAID) and the Johns Hopkins University School of Medicine.
"This was an attempt to test one important recent hypothesis about what causes CFS," says NIAID co-author Stephen Straus, M.D., who also serves as director of the National Center for Complementary and Alternative Medicine at the National Institutes of Health (NIH). "The results do not completely negate NMH's role in a subset of CFS patients, but it clearly tells us that fludrocortisone by itself is insufficient to alleviate that form of low blood pressure or other symptoms of CFS in the patients we studied."
CFS is estimated to afflict up to 400 per 100,000 adults in the United States as well as a proportionally smaller number of adolescents and children. Although debilitating fatigue is the hallmark of the syndrome, memory and sleeping problems, muscle aches and other symptoms make the ordinary activities of daily living a struggle for many people with CFS. Because scientists have not yet pinpointed the cause of CFS, treatment is targeted to specific symptoms, such as the lightheadedness that prompted the investigation of fludrocortisone as a possible remedy.
In a pilot study conducted in the mid-1990s, Peter Rowe, M.D., a Hopkins pediatrician and co-author of the new report, gave some people with CFS and NMH fludrocortisone or other drugs and found that their CFS symptoms improved. Because fludrocortisone appeared to be the most promising, Dr. Rowe began a collaboration with the NIAID team to rigorously test the hypothesis that NMH might be an underlying and treatable cause of CFS symptoms.
The two centers together screened 750 applicants and winnowed this group down to 171 potentially eligible, moderately ill adult CFS patients. Of those, 100 enrolled in the study after also being diagnosed with NMH by a two-stage tilt-table test performed by the Hopkins group. During the test, the volunteer lies on a table and is loosely held in place by safety straps and a footboard. The table is then tilted upright to 70 degrees for up to 45 minutes, and after a brief respite, for as much as 15 minutes more. During either stage, the investigator stops the test if the volunteer faints or develops low blood pressure.
The 100 participants were randomly divided into two groups. Half received fludrocortisone (0.1 milligram per day) and half received placebo for nine weeks. Neither the participants nor the study team know which regimen the patients received. Based on standardized, daily self-ratings of overall wellness and other measures of illness severity, however, they experienced no significant difference in benefit: 14 percent of those treated with fludrocortisone had a notable improvement in overall well-being compared with 10 percent of those in the placebo group.
This is the largest and only randomized, placebo-controlled study to investigate the potential role of NMH in CFS. Since 1996 when the study began, well-designed clinical trials have found that four different drugs, some of which have a more direct effect on blood pressure, can benefit some people who don't have CFS but who experience recurrent fainting due to NMH. According to Dr. Rowe, these studies provide a rationale for testing such treatments in patients with CFS and NMH.
"CFS is a complex and debilitating disorder," Dr. Straus concludes, "and serious research efforts at NIH and elsewhere continue in an effort to understand how it occurs and how best to treat it."
NIAID is a component of NIH. NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov.