Clinical Trial – Page 28 – American ME and CFS Society

A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a physically debilitating illness associated with immunologic abnormalities, viral reactivation, and impairment of cognition.

In a randomized, multicenter, placebo-controlled, double-blind study of 92 patients meeting the CFS case definition of the Centers for Disease Control and Prevention, the response of several laboratory and clinical variables to an antiviral and immunomodulatory drug, poly(I).poly(C12U), was determined.

Measures of clinical response included Karnofsky performance score, a cognition scale derived from a self-administered instrument assessing symptomatology (SCL-90-R), an activities of daily living scale, and exercise treadmill performance.

After 24 weeks, patients receiving poly(I).poly(C12U) had higher scores for both global performance and perceived cognition than did patients receiving placebo. In particular, patients given poly(I).poly(C12U) had increased Karnofsky performance scores (P < .03), exhibited a greater ability to do work during exercise treadmill testing (P = .01), displayed an enhanced capacity to perform the activities of daily living (P < .04), had a reduced cognitive deficit (P = .05), and required less use of other medications (P < .05).

Source: Strayer DR, Carter WA, Brodsky I, Cheney P, Peterson D, Salvato P, Thompson C, Loveless M, Shapiro DE, Elsasser W, et al. A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S88-95. http://www.ncbi.nlm.nih.gov/pubmed/8148460

Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial

Abstract:

PURPOSE: To evaluate the potential benefit of immunologic therapy with dialyzable leukocyte extract and psychologic treatment in the form of cognitive-behavioral therapy (CBT) in patients with chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: Immunologic and psychologic treatments were administered to 90 adult patients who fulfilled diagnostic criteria for CFS in a double-blind, randomized, and placebo-controlled study. A four-cell trial design allowed the assessment of benefit from immunologic and psychologic treatment individually or in combination. Outcome was evaluated by measurement of global well-being (visual analogue scales), physical capacity (standardized diaries of daily activities), functional status (Karnofsky performance scale), and psychologic morbidity (Profile of Mood States questionnaire), and cell-mediated immunity was evaluated by peripheral blood T-cell subset analysis and delayed-type hypersensitivity skin testing.

RESULTS: Neither dialyzable leukocyte extract nor CBT (alone or in combination) provided greater benefit than the nonspecific treatment regimens.

CONCLUSIONS: In this study, patients with CFS did not demonstrate a specific response to immunologic and/or psychologic therapy. The improvement recorded in the group as a whole may reflect both nonspecific treatment effects and a propensity to remission in the natural history of this disorder.

Comment in:

Treatment for chronic fatigue syndrome. [Am J Med. 1994]

Cognitive behavior therapy for chronic fatigue syndrome. [Am J Med. 1995]

Source: Lloyd AR, Hickie I, Brockman A, Hickie C, Wilson A, Dwyer J, Wakefield D. Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial. Am J Med. 1993 Feb;94(2):197-203. http://www.ncbi.nlm.nih.gov/pubmed/8430715

Bupropion treatment of fluoxetine-resistant chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) includes many symptoms of major depression. For this reason, many antidepressants have been used to treat the symptoms of this disorder. Among the more recently released antidepressants are fluoxetine and bupropion.

In this open study, nine CFS patients who either could not tolerate or did not respond to fluoxetine showed significant response when administered 300 mg/day of bupropion for an 8-week period in both rating of HDRS (t = 4.80, p < 0.01) and BDI (t = 2.48, p < 0.05). Furthermore, bupropion improvement in Hamilton Depression Rating Scale correlated significantly with change in plasma homovanillic acid (HVA) (r = 0.96, p < 0.01).

Plasma total methylhydroxyphenolglycol (MHPG) also increased significantly during bupropion treatment (t = 2.37, p = 0.05). Measures of T1 microsomal antibodies also decreased over treatment time; increases in natural killer cell numbers correlated inversely with change in plasma levels of free MHPG (r = -0.88, p < 0.05). Bupropion responders were more likely to have trough blood levels above 30 ng/ml (chi 2 = 3.6, p = 0.05).

Source: Goodnick PJ, Sandoval R, Brickman A, Klimas NG. Bupropion treatment of fluoxetine-resistant chronic fatigue syndrome. Biol Psychiatry. 1992 Nov 1;32(9):834-8. http://www.ncbi.nlm.nih.gov/pubmed/1450297

Chronic Fatigue Syndrome: Do herbs or homeopathy help?

Abstract:

To determine the effect of certain herbal and homeopathic preparations on symptoms, lymphocyte markers, and cytotoxic function of the lymphocytes in patients with chronic fatigue syndrome, we studied six outpatients diagnosed with the disease by their family physicians. Patients were given herbal and homeopathic preparations after a 3-week symptom-recording period. After treatment, symptoms were again recorded. Blood samples were taken before and after treatment. None of the values showed any significant change after treatment.

Source: Leyton E, Pross H. Chronic Fatigue Syndrome: Do herbs or homeopathy help? Can Fam Physician. 1992 Sep;38:2021-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2145466/ (Full article)

Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome

Abstract:

Associations between immunological and psychological dysfunction in 33 patients with Chronic Fatigue Syndrome (CFS) were examined before and in response to treatment in a double blind, placebo-controlled trial of high dose intravenous immunoglobulin. Only those patients who received active immunotherapy demonstrated a consistent pattern of correlations between improvement in depressive symptoms and markers of cell-mediated immunity (CMI).

This finding lends some support to the hypothesis that depressive symptoms in patients with CFS occur secondary to, or share a common pathophysiology with, immunological dysfunction. This pattern and the lack of strong associations between depression and immunological disturbance prior to treatment are less supportive of the view that CFS is primarily a form of depressive disorder or that immunological dysfunction in patients with CFS is secondary to concurrent depression.

Source: Hickie I, Lloyd A, Wakefield D. Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome. Aust N Z J Psychiatry. 1992 Jun;26(2):249-56. http://www.ncbi.nlm.nih.gov/pubmed/1642616

Red blood cell magnesium and chronic fatigue syndrome

Abstract:

The hypotheses that patients with chronic fatigue syndrome (CFS) have low red blood cell magnesium and that magnesium treatment would improve the wellbeing of such patients were tested in a case-control study and a randomised, double-blind, placebo-controlled trial, respectively.

In the case-control study, 20 patients with CFS had lower red cell magnesium concentrations than did 20 healthy control subjects matched for age, sex, and social class (difference 0.1 mmol/l, 95% confidence interval [CI] 0.05 to 0.15).

In the clinical trial, 32 patients with CFS were randomly allocated either to intramuscular magnesium sulphate every week for 6 weeks (15 patients) or to placebo (17).

Patients treated with magnesium claimed to have improved energy levels, better emotional state, and less pain, as judged by changes in the Nottingham health profile. 12 of the 15 treated patients said that they had benefited from treatment, and in 7 patients energy score improved from the maximum to the minimum.

By contrast, 3 of the 17 patients on placebo said that they felt better (difference 62%, 95% CI 35 to 90), and 1 patient had a better energy score. Red cell magnesium returned to normal in all patients on magnesium but in only 1 patient on placebo. The findings show that magnesium may have a role in CFS.

Comment in:

Magnesium and chronic fatigue. [Lancet. 1991]

Magnesium and chronic fatigue syndrome. [Lancet. 1991]

Intravenous magnesium loading in chronic fatigue syndrome. [Lancet. 1992]

Source: Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet. 1991 Mar 30;337(8744):757-60. http://www.ncbi.nlm.nih.gov/pubmed/1672392

A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome

Abstract:

PURPOSE: Currently, there is no established therapy for chronic fatigue syndrome (CFS), a recently defined illness that has been associated with a variety of immunologic abnormalities. Based on the hypothesis that a chronic viral infection or an immunoregulatory defect is involved in the pathogenesis of CFS, the therapeutic benefit of intravenous immunoglobulin G (IV IgG) was evaluated in a group of patients with CFS. Additionally, serum immunoglobulin concentrations and peripheral blood lymphocyte subset numbers were measured at the outset of the study, and the effect of IV IgG therapy on IgG subclass levels was determined.

PATIENTS AND METHODS: Thirty patients with CFS were enrolled in a double-blind, placebo-controlled trial of IV IgG. The treatment regimen consisted of IV IgG (1 g/kg) or intravenous placebo (1% albumin solution) administered every 30 days for 6 months. Participants completed a self-assessment form prior to each of the six treatments, which was used to measure severity of symptoms, functional status, and health perceptions. Patients were also asked to report adverse experiences defined as worsening of symptoms occurring within 48 hours of each treatment.

RESULTS: Twenty-eight patients completed the trial. At baseline, all 28 patients complained of moderate to severe fatigue, and measures of social functioning and health perceptions showed marked impairment. Low levels of IgG1 were found in 12 (42.9%), and 18 (64.3%) had low levels of IgG3. At the end of the study, no significant therapeutic benefit could be detected in terms of symptom amelioration or improvement in functional status, despite restoration of IgG1 levels to a normal range. Major adverse experiences were observed in 20% of both the IV IgG and placebo groups.

CONCLUSION: The results of this study indicate that IV IgG is unlikely to be of clinical benefit in CFS. In addition to the ongoing need for placebo-controlled trials of candidate therapies for CFS, an expanded research effort is needed to define the etiology and pathogenesis of this disorder.

Comment in:

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

Source: Peterson PK, Shepard J, Macres M, Schenck C, Crosson J, Rechtman D, Lurie N. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Am J Med. 1990 Nov;89(5):554-60. http://www.ncbi.nlm.nih.gov/pubmed/2239975

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