Category: Clinical Trial

Randomized controlled trial of Siberian ginseng for chronic fatigue

Abstract:

BACKGROUND: Chronic fatigue greatly affects quality of life and is a common reason for consulting a physician. Since conventional therapy is often of limited help, fatigued patients may use herbal treatments. This randomized controlled trial evaluated the effectiveness of Siberian ginseng.

METHOD: Subjects were recruited from advertisements in Iowa (82%) and members of chronic fatigue syndrome support groups (18%). Potential subjects were required to have substantial fatigue > or = 6 months with no identifiable cause. The mean change in a fatigue measure was compared for placebo and Siberian ginseng at 1 and 2 months. Comparisons were for all subjects and for subjects with characteristics previously identified in the literature as important for categorizing chronic fatigue.

RESULTS: Ninety-six subjects were randomized to treatment groups, and 76 provided information at 2 months of follow-up. Fatigue among subjects assigned to either placebo or Siberian ginseng was substantially reduced during the study, but differences between treatment groups were not statistically significant in the full sample. Fatigue severity and duration had a statistically significant interaction with response to Siberian ginseng at the P < 0.05 level. Treatment was effective at 2 months for 45 subjects with less severe fatigue (P = 0.04 unadjusted for multiple comparisons) and for 41 subjects with fatigue for > or = 5 years (P = 0.09 unadjusted for multiple comparisons).

CONCLUSION: Overall efficacy was not demonstrated. However, the findings of possible efficacy for patients with moderate fatigue suggests that further research may be of value.

 

Source: Hartz AJ, Bentler S, Noyes R, Hoehns J, Logemann C, Sinift S, Butani Y, Wang W, Brake K, Ernst M, Kautzman H. Randomized controlled trial of Siberian ginseng for chronic fatigue. Psychol Med. 2004 Jan;34(1):51-61. http://www.ncbi.nlm.nih.gov/pubmed/14971626

 

Is graded exercise better than cognitive behaviour therapy for fatigue? A UK randomized trial in primary care

Abstract:

BACKGROUND: Patients frequently present with unexplained fatigue in primary care, but there have been few treatment trials in this context. We aimed to test cognitive behaviour therapy (CBT) and graded exercise therapy (GET) for patients presenting to their family doctor with fatigue. Secondly, we described the outcome for a cohort of patients who presented to the same doctors with fatigue, who received standard care, plus a booklet.

METHOD: This was a randomized trial, followed by a prospective cohort study. Twenty-two practices in SE England referred 144 patients aged 16 to 75 years with over 3 months of unexplained fatigue. Self-rated fatigue score, the hospital anxiety and depression rating scale, functional impairment, physical step-test performance and causal attributions were measured. In the trial six sessions of CBT or GET were randomly allocated.

RESULTS: In the therapy groups the mean fatigue score decreased by 10 points (95% confidence interval (CI) = -25 to -15), with no significant difference between groups (mean difference = -1.3; CI = -3.9 to 1.3). Fewer patients attended for GET. At outcome one-half of patients had clinically important fatigue in both randomized groups, but patients in the group offered CBT were less anxious. Twenty-seven per cent of the patients met criteria for CFS at baseline. Only 25% of this subgroup recovered, compared to 60% of the subgroup that did not meet criteria for CFS.

CONCLUSIONS: Short courses of GET were not superior to CBT for patients consulting with fatigue of over 3 months in primary care. CBT was easier ‘to sell’. Low recovery in the CFS subgroup suggests that brief treatment is too short.

 

Source: Ridsdale L, Darbishire L, Seed PT. Is graded exercise better than cognitive behaviour therapy for fatigue? A UK randomized trial in primary care. Psychol Med. 2004 Jan;34(1):37-49. http://www.ncbi.nlm.nih.gov/pubmed/14971625

 

Quality of life and symptom severity for individuals with chronic fatigue syndrome: findings from a randomized clinical trial

Abstract:

OBJECTIVE: Chronic fatigue syndrome is a profoundly disabling condition characterized by severe, unrelenting fatigue and a number of other physical and cognitive symptoms. Currently, there is no cure or widely accepted treatment for chronic fatigue syndrome, and few rehabilitation programs exist to address quality of life issues in chronic fatigue syndrome. In the present randomized clinical trial, the effects of an integrative, consumer-driven rehabilitation program on quality of life and symptom severity for individuals with chronic fatigue syndrome were examined.

METHOD: Forty-seven participants were randomly assigned to either an immediate program group (n = 23) or a delayed program control group (n = 24) and assessed with the Chronic Fatigue Syndrome Symptom Rating Scale and the Quality of Life Index before the program, after program participants completed the group phase, and after program participants completed the one-on-one phase. It was hypothesized that the program would lead to improvements in quality of life and an overall reduction in symptom severity.

RESULTS: Linear growth models were estimated comparing program and control conditions over time using random-effects regression analyses. Significant condition by time interactions were observed for the main outcomes of symptom severity and overall quality of life. Effect sizes for these interactions involving symptom severity (Cohen’s d = 0.71) and overall quality of life (Cohen’s d = .66) were moderate.

CONCLUSIONS: Findings indicate that consumer driven programs such as this one can have a positive impact on symptom severity and quality of life over time for individuals with chronic fatigue syndrome.

 

Source: Taylor RR. Quality of life and symptom severity for individuals with chronic fatigue syndrome: findings from a randomized clinical trial. Am J Occup Ther. 2004 Jan-Feb;58(1):35-43. http://www.ncbi.nlm.nih.gov/pubmed/14763634

 

Immune modulation with a staphylococcal preparation in fibromyalgia/chronic fatigue syndrome: relation between antibody levels and clinical improvement

Abstract:

The aims of this study were to evaluate the serological response to treatment with staphylococcal vaccine in fibromyalgia/chronic fatigue syndrome patients and to explore the relationship between serological response and clinical effect.

Twenty-eight patients, half of whom served as controls, were recruited from a 6-month randomised trial in which repeated administration of the staphylococcal toxoid vaccine Staphypan Berna (Berna Biotech, Switzerland) was tested against placebo. Antibody status against extracellular toxins/enzymes, cell-wall components, and enterotoxins was evaluated at baseline and at endpoint. The clinical response to treatment was recorded in rating scales.

In the group receiving active treatment, significant serological changes were recorded, whereas no significant changes were found in controls. Treatment led to a significantly increased capacity of serum to neutralise alpha-toxin and a significant increase in serum IgG to alpha-toxin and lipase. Furthermore, the increase in these parameters combined paralleled the improvement in clinical outcome. Thus, the greater the serological response, the greater was the clinical effect.

In conclusion, this explorative study has shown that repeated administration of the Staphypan Berna vaccine in patients with fibromyalgia/chronic fatigue syndrome causes a serological response to several staphylococcal antigens, particularly to certain extracellular toxins and enzymes. The results further show that this response is related to the clinical outcome of treatment.

 

Source: Zachrisson O, Colque-Navarro P, Gottfries CG, Regland B, Möllby R. Immune modulation with a staphylococcal preparation in fibromyalgia/chronic fatigue syndrome: relation between antibody levels and clinical improvement. Eur J Clin Microbiol Infect Dis. 2004 Feb;23(2):98-105. Epub 2004 Jan 20. http://www.ncbi.nlm.nih.gov/pubmed/14735403

 

The effect of granisetron, a 5-HT3 receptor antagonist, in the treatment of chronic fatigue syndrome patients–a pilot study

Abstract:

OBJECTIVE: To explore the effect of granisetron, a 5-HT3 antagonist, on fatigue and functional impairment in patients with chronic fatigue syndrome (CFS).

METHODS: Five female patients were eligible to receive oral granisetron for one month (1 mg a day for the first two weeks and 2 mg a day for the second two weeks). The patients had to be between 18 and 65 years of age and suffering from CFS according to the CDC criteria. The effect was assessed by pre- and post-testing, using validated instruments designed to assess the different dimensions of CFS. Treatment response was also evaluated by visual analogue scales (VAS) for fatigue. Analysis was based on intention to treat.

RESULTS: Treatment with granisetron resulted in significant improvement in fatigue severity and functional impairment. Activity level showed no significant increase.

CONCLUSION: The promising results of this study have encouraged us to perform a placebo-controlled, double-blind study to evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.

Comment in: Pilot studies: one swallow does not make a summer… [Neth J Med. 2003]

 

Source: The GK, Prins J, Bleijenberg G, van der Meer JW. The effect of granisetron, a 5-HT3 receptor antagonist, in the treatment of chronic fatigue syndrome patients–a pilot study.  Neth J Med. 2003 Sep;61(9):285-9. http://www.njmonline.nl/getpdf.php?id=16 (Full article)

 

Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports

Abstract:

Chronic fatigue syndrome (CFS) is characterized by persistent mental and physical fatigue for at least 6 months. Its pathophysiology is unknown and there is no proven effective treatment. We describe three cases who fulfill the criteria of CFS, in whom a defect of neuromuscular transmission and dysautonomia are present and who respond to acetylcholine-esterase inhibition.

Case 1: 18-year-old female with a 3-year history of CFS. Response of compound-muscle-action potential, recorded using surface recording electrode, over left abductor pollicis brevis muscle, to repetitive nerve stimulation (RNS) at a rate of 10 Hz showed a 42% incremental response. Composite autonomic scoring system (CASS) showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2). Serological tests for Epstein-Barr virus (EBV) revealed positive antiviral capsid antigens (anti-VCA) immunoglobulins G (IgG). Oral pyridostigmine therapy (30 mg) resulted in marked improvement in symptoms.

Case 2: 28-year-old female with 10-year history of CFS. RNS, using identical protocol, showed a 60% incremental response over the same muscle. CASS showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2) and this patient was also positive for EBV. This patient responded dramatically to 10-mg pyridostigmine.

Case 3: 29-year-old female with a history of CFS for longer than 15 years. Repetitive stimulation, using identical paradigm to left abductor pollicis brevis muscle, showed a 42% incremental response. CASS showed mildly cholinergic impairment (cardiovagal score: 2; sudomotor score: 1). EBV antibody titers were positive. Patient responded to 30-mg pyridostigmine with an improvement in her fatigue.

These three cases generate the hypothesis that the fatigue in some patients with clinical CFS might be due to a combination of mild neuromuscular transmission defect combined with cholinergic dysautonomia. Support for this thesis derives from the improvement with cholinesterase inhibition.

 

Source: Kawamura Y, Kihara M, Nishimoto K, Taki M. Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports. Pathophysiology. 2003 May;9(3):189-194. http://www.ncbi.nlm.nih.gov/pubmed/14567934

 

Effect of topical nasal corticosteroids on patients with chronic fatigue syndrome and rhinitis

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling illness of persistent fatigue. Recent studies have shown that patients with CFS have an increased prevalence of nonallergic rhinitis. Inflammation of the nasal passages due to allergic rhinitis can cause nasal congestion resulting in an increased number of sleep disturbances and daytime fatigue. While topical nasal corticosteroids have been shown to alleviate nasal obstruction effectively in patients with rhinitis who do not have CFS, it is unknown whether topical nasal corticosteroids will reduce CFS symptoms.

STUDY OBJECTIVE: The purpose of this study is to determine whether topical nasal corticosteroids will reduce daytime sleepiness in patients with CFS and rhinitis.

METHODS: Twenty-eight of 31 subjects with rhinitis and a diagnosis of CFS completed the double-blind, randomized, placebo-controlled trial. Two subjects failed screening, and 3 subjects withdrew from the study prior to its completion. Subjects were randomized according to Balaam’s crossover design, and one of the following interventions was used for each group in the study: 8-week treatment with a topical nasal corticosteroid, 8-week treatment with a placebo saline spray, 4-week treatment with a topical nasal corticosteroid followed by a 4-week treatment with a placebo saline spray, or a 4-week treatment with a placebo saline spray followed by a 4-week treatment with a topical nasal corticosteroid. Data focusing on rhinitis symptoms, severity of chronic fatigue symptoms, and quality of life were gathered at biweekly office visits and with daily diaries.

RESULTS: The results indicated that daytime sleepiness was reduced when patients with rhinitis and CFS were treated with topical nasal corticosteroids. The severity of associated CFS symptoms, specifically fatigue, muscle pain, postexertional fatigue, and daily activity, did not improve with treatment.

CONCLUSION: Treating the symptoms of rhinitis in patients with CFS does not appear to alleviate daytime fatigue or associated nasal, musculoskeletal, or cognitive complaints. Therefore, it is unlikely that aggressive treatment of such symptoms with topical nasal corticosteroids will provide significant benefit to patients with CFS who do not have allergic rhinitis. These results indicate that the nonallergic rhinitis seen in patients with CFS may arise from a mechanism other than chronic inflammation.

 

Source: Kakumanu SS, Mende CN, Lehman EB, Hughes K, Craig TJ. Effect of topical nasal corticosteroids on patients with chronic fatigue syndrome and rhinitis. J Am Osteopath Assoc. 2003 Sep;103(9):423-7. http://www.ncbi.nlm.nih.gov/pubmed/14527077

 

Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study

Abstract:

PURPOSE: Chronic fatigue syndrome has been associated with decreased function of the hypothalamic-pituitary-adrenal axis. Although neurally mediated hypotension occurs more frequently in patients with chronic fatigue syndrome than in controls, attempts to alleviate symptoms by administration of hydrocortisone or fludrocortisone have not been successful. The purpose of this study was to investigate the effect of combination therapy (5 mg/d of hydrocortisone and 50 microg/d of 9-alfa-fludrocortisone) on fatigue and well-being in chronic fatigue syndrome.

METHODS: We performed a 6-month, randomized, placebo-controlled, double-blind, crossover study in 100 patients who fulfilled the 1994 Centers for Disease Control and Prevention criteria for chronic fatigue syndrome. Between-group differences (placebo minus treatment) were calculated on a 10-point visual analog scale.

RESULTS: Eighty patients completed the 3 months of placebo and 3 months of active treatment in a double-blind fashion. There were no differences between treatment and placebo in patient-reported fatigue (mean difference, 0.1; 95% confidence interval [CI]: -0.3 to 0.6) or well-being (mean difference, -0.4; 95% CI: -1.0 to 0.1). There were also no between-group differences in fatigue measured with the Abbreviated Fatigue Questionnaire, the Short Form-36 Mental or Physical Factor scores, or in the Hospital Anxiety and Depression Scale.

CONCLUSION: Low-dose combination therapy of hydrocortisone and fludrocortisone was not effective in patients with chronic fatigue syndrome.

 

Source: Blockmans D, Persoons P, Van Houdenhove B, Lejeune M, Bobbaers H. Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study. Am J Med. 2003 Jun 15;114(9):736-41. http://www.ncbi.nlm.nih.gov/pubmed/12829200

 

A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function

Abstract:

This study was designed to determine safety and efficacy of a 6-month trial of valacyclovir in single-virus Epstein-Barr virus (EBV) persistent infection. Phase I of this study used four specific criteria to define a subset of patients with chronic fatigue syndrome (CFS). In the second phase, myocardial dynamics were measured by MUGA rest/stress radionuclide ventriculographic (RVG) examinations pre- and posttreatment with valacyclovir.

In phase I, a trial was performed in 19 consecutive CFS patients with the following diagnostic conditions: patients met criteria for diagnosis of CFS; they had had CFS for less than 1 year. They demonstrated repetitively abnormal oscillating T waves (ischemic or flat) at 24-h Holter monitoring; and they had elevated serum IgM antibody titers to EBV viral capsid antigen and/or total diffuse early antigen as measured by the enzyme-linked immunosorbent assay method.

The treatment group comprised 10 CFS patients with no serum antibodies to human cytomegalovirus, but the control group (nine CFS patients) had, additionally, high titers of serum antibodies (IgG) to conformational structural antigens of human cytomegalovirus. Both the parallel treatment and control CFS groups received valacyclovir 1.0-1.5 gm q.6.h. for 6 months.

This valacyclovir dose achieved serum acyclovir C(max) of > 7 microm and high antiviral activity versus EBV (IC(50) of 4.4-13.3 m). In phase II, six additional CFS patients met the same four criteria as the 19 CFS patients in phase I. They had, however, been ill for a mean of 55.8 months. Thus, 25 CFS patients comprise this study.

The studies were carried out at a single outpatient practice in Birmingham, MI, U.S.A. Before initiating valacyclovir, and after 6 months of treatment, clinical and laboratory observations were made. The CFS Energy Index point score (Table I) was used to record each CFS patient’s functional capacity at baseline and after 1, 3 and 6 months of valacyclovir. Energy Index point scores, as well as EBV and human cytomegalovirus serum antibody titers were assessed.

In the second phase, left ventricular dynamics were repeated after 6 months of treatment with valacyclovir. We concluded that the 16 CFS patients (included in both phases of this study) with EBV-persistent infection (EBV single-virus subset) are improved after 6 months of continuous pharmacokinetic dosing with valacyclovir. Nine CFS patients with EBV/human cytomegalovirus co-infection did not benefit from 6 months of similar treatment. Valacyclovir is not an effective anti-human cytomegalovirus antiviral drug. Unimproved CFS patients with co-infections EBV and human cytomegalovirus may require combined treatment with valacyclovir and another drug more active against human cytomegalovirus.

This preliminary trial, with a small number of patients, may be critical to an appropriately designed larger, double-blind, placebo-controlled trial.

Copyright 2002 Prous Science

 

Source: Lerner AM, Beqaj SH, Deeter RG, Dworkin HJ, Zervos M, Chang CH, Fitzgerald JT, Goldstein J, O’Neill W. A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function. Drugs Today (Barc). 2002 Aug;38(8):549-61. http://www.ncbi.nlm.nih.gov/pubmed/12582420

 

A pilot randomized controlled trial of dexamphetamine in patients with chronic fatigue syndrome

Abstract:

This study determined whether dexamphetamine improved symptoms and quality of life in patients with chronic fatigue syndrome. The setting was a specialized clinic within a tertiary referral hospital. This was a 6-week parallel-group, placebo-controlled trial with random allocation. There was a 2-week dose-adjustment phase and a 4-week stable treatment period. Outcome measures were the Fatigue Severity Scale, the Medical Outcomes Study 36-item Short-Form Health Survey, and two patient-determined outcomes. Ten patients were randomly assigned to dexamphetamine, and 10 were assigned to placebo. Fatigue Severity Scale scores improved in nine of 10 dexamphetamine and four of 10 placebo patients. The change in mean score was statistically significant. There were large but statistically nonsignificant changes in scores for the Short-Form Health Survey domains vitality and physical functioning. Dexamphetamine may be useful in the management of chronic fatigue syndrome; a larger and longer trial is justified by these results.

 

Source: Olson LG, Ambrogetti A, Sutherland DC. A pilot randomized controlled trial of dexamphetamine in patients with chronic fatigue syndrome. Psychosomatics. 2003 Jan-Feb;44(1):38-43. http://www.ncbi.nlm.nih.gov/pubmed/12515836