Category: Clinical Trial

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome

Abstract:

PURPOSE: The chronic fatigue syndrome (CFS) is characterized by profound fatigue, neuropsychiatric dysfunction, and frequent abnormalities in cell-mediated immunity. No effective therapy is known.

PATIENTS AND METHODS: Forty-nine patients (40 with abnormal cell-mediated immunity) participated in a randomized, double-blind, placebo-controlled trial to determine the effectiveness of high-dose intravenously administered immunoglobulin G. The patients received three intravenous infusions of a placebo solution or immunoglobulin at a dose of 2 g/kg/month. Assessment of the severity of symptoms and associated disability, both before and after treatment, was completed at detailed interviews by a physician and psychiatrist, who were unaware of the treatment status. In addition, any change in physical symptoms and functional capacity was recorded using visual analogue scales, while changes in psychologic morbidity were assessed using patient-rated indices of depression. Cell-mediated immunity was evaluated by T-cell subset analysis, delayed-type hypersensitivity skin testing, and lymphocyte transformation with phytohemagglutinin.

RESULTS: At the interview conducted by the physician 3 months after the final infusion, 10 of 23 (43%) immunoglobulin recipients and three of the 26 (12%) placebo recipients were assessed as having responded with a substantial reduction in their symptoms and recommencement of work, leisure, and social activities. The patients designated as having responded had improvement in physical, psychologic, and immunologic measures (p less than 0.01 for each).

CONCLUSION: Immunomodulatory treatment with immunoglobulin is effective in a significant number of patients with CFS, a finding that supports the concept that an immunologic disturbance may be important in the pathogenesis of this disorder.

Comment in:

Intravenous immunoglobulin treatment for the chronic fatigue syndrome. [Am J Med. 1990]

Immunoglobulin treatment for chronic fatigue syndrome. [Am J Med. 1991]

Intravenous immunoglobulin treatment of chronic fatigue syndrome. [Am J Med. 1991]

Placebo responses in patients complaining of chronic fatigue. [Am J Med. 1991]

 

Source: Lloyd A, Hickie I, Wakefield D, Boughton C, Dwyer J. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.  Am J Med. 1990 Nov;89(5):561-8. http://www.ncbi.nlm.nih.gov/pubmed/2146875

 

Effect of high doses of essential fatty acids on the postviral fatigue syndrome

Abstract:

Sixty-three adults with the diagnosis of the postviral fatigue syndrome were enrolled in a double-blind, placebo-controlled study of essential fatty acid therapy. The patients had been ill for from one to three years after an apparently viral infection, suffering from severe fatigue, myalgia and a variety of psychiatric symptoms.

The preparation given contained linoleic, gamma-linolenic, eicosapentaenoic and docosahexaenoic acids and either it, or the placebo, was given as 8 x 500 mg capsules per day over a 3-month period. The trial was parallel in design and patients were evaluated at entry, one month and three months. In consultation with the patient the doctors assessed overall condition, fatigue, myalgia, dizziness, poor concentration and depression on a 3-point scale. The essential fatty acid composition of their red cell membrane phospholipids was analysed at the first and last visits.

At 1 month, 74% of patients on active treatment and 23% of those on placebo assessed themselves as improved over the baseline, with the improvement being much greater in the former. At 3 months the corresponding figures were 85% and 17% (p less than 0.0001) since the placebo group had reverted towards the baseline state while those in the active group showed continued improvement.

The essential fatty acid levels were abnormal at the baseline and corrected by active treatment. There were no adverse events. We conclude that essential fatty acids provide a rational, safe and effective treatment for patients with the post-viral fatigue syndrome.

 

Source:  Behan PO, Behan WM, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand. 1990 Sep;82(3):209-16. http://www.ncbi.nlm.nih.gov/pubmed/2270749

 

Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is a recently defined entity for which clinical criteria were proposed by the Centers for Disease Control, Atlanta, Ga. A frequently advocated treatment in Southern California is an injectable solution of bovine liver extract containing folic acid and cyanocobalamin (LEFAC).

We conducted a double-blind, placebo-controlled, crossover trial of intramuscular LEFAC in 15 patients who met the Centers for Disease Control criteria for chronic fatigue syndrome. Although patients responded to placebo and LEFAC by several criteria of functional status, no significant difference was apparent between response to placebo and that to LEFAC. The placebo response appeared to be strong.

 

Source: Kaslow JE, Rucker L, Onishi R. Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome. Arch Intern Med. 1989 Nov;149(11):2501-3. http://www.ncbi.nlm.nih.gov/pubmed/2684076

 

Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial

Abstract:

Twenty-seven adults with a diagnosis of the chronic fatigue syndrome were enrolled in a double-blind, placebo-controlled study of acyclovir therapy. The patients had had debilitating fatigue for an average of 6.8 years, accompanied by persisting antibodies to Epstein-Barr virus early antigens (titers greater than or equal to 1:40) or undetectable levels of antibodies to Epstein-Barr virus nuclear antigens (titers less than 1:2) or both.

Each course of treatment consisted of intravenous placebo or acyclovir (500 mg per square meter of body-surface area) administered every eight hours for seven days. The same drug was then given orally for 30 days (acyclovir, 800 mg four times daily). There were six-week observation periods before, between, and after the treatments. Three patients had acyclovir-induced nephrotoxicity and were withdrawn from the study.

Of the 24 patients who completed the trial, similar numbers improved with acyclovir therapy and with placebo (11 and 10, respectively). Neither acyclovir treatment nor clinical improvement correlated with alterations in laboratory findings, including titers of antibody to Epstein-Barr virus or levels of circulating immune complexes or of leukocyte 2′,5′-oligoadenylate synthetase. Subjective improvement correlated with various measures of mood.

We conclude that acyclovir, as used in this study, does not ameliorate the chronic fatigue syndrome. We believe that the clinical improvement observed in most patients reflected either spontaneous remission of the syndrome or a placebo effect.

 

Source: Straus SE, Dale JK, Tobi M, Lawley T, Preble O, Blaese RM, Hallahan C, Henle W. Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial. N Engl J Med. 1988 Dec 29;319(26):1692-8. http://www.ncbi.nlm.nih.gov/pubmed/2849717