Category: Clinical Trial

Fatigue Intervention by Nurses Evaluation–the FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol.[ISRCTN74156610]

Abstract:

BACKGROUND: Chronic fatigue syndrome, also known as ME (CFS/ME), is a condition characterised primarily by severe, disabling fatigue, of unknown origin, which has a poor prognosis and serious personal and economic consequences. Evidence for the effectiveness of any treatment for CFS/ME in primary care, where most patients are seen, is sparse. Recently, a brief, pragmatic treatment for CFS/ME, based on a physiological dysregulation model of the condition, was shown to be successful in improving fatigue and physical functioning in patients in secondary care. The treatment involves providing patients with a readily understandable explanation of their symptoms, from which flows the rationale for a graded rehabilitative plan, developed collaboratively with the therapist. The present trial will test the effectiveness and cost-effectiveness of pragmatic rehabilitation when delivered by specially trained general nurses in primary care. We selected a client-centred counselling intervention, called supportive listening, as a comparison treatment. Counselling has been shown to be as effective as cognitive behaviour therapy for treating fatigue in primary care, is more readily available, and controls for supportive therapist contact time. Our control condition is treatment as usual by the general practitioner (GP).

METHODS AND DESIGN: This study protocol describes the design of an ongoing, single-blind, pragmatic randomized controlled trial of a brief (18 week) self-help treatment, pragmatic rehabilitation, delivered by specially trained nurse-therapists in patients’ homes, compared with nurse-therapist delivered supportive listening and treatment as usual by the GP. An economic evaluation, taking a societal viewpoint, is being carried out alongside the clinical trial. Three adult general nurses were trained over a six month period to deliver the two interventions. Patients aged over 18 and fulfilling the Oxford criteria for CFS are assessed at baseline, after the intervention, and again one year later. Primary outcomes are self-reported physical functioning and fatigue at one year, and will be analysed on an intention-to-treat basis. A qualitative study will examine the interventions’ mechanisms of change, and also GPs’ drivers and barriers towards referral.

 

Source: Wearden AJ, Riste L, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, Dunn G, Richardson G, Lovell K, Powell P. Fatigue Intervention by Nurses Evaluation–the FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol. [ISRCTN74156610]. BMC Med. 2006 Apr 7;4:9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1456982/ (Full article)

 

Does methylphenidate reduce the symptoms of chronic fatigue syndrome?

Abstract:

PURPOSE: Chronic fatigue syndrome is a clinical entity consisting of prolonged and debilitating fatigue in which concentration disturbances are very frequent. Until now, no medical treatment has shown any efficacy. The objectives of this study were to investigate the short-term effects of methylphenidate, an amphetamine derivative, on fatigue, concentration disturbances, and quality of life.

SUBJECTS AND METHODS: A double-blind randomized placebo-controlled crossover study was conducted in 60 patients who fulfilled the 1994 Centers for Disease Control criteria for chronic fatigue syndrome and had concentration difficulties. Patients were enrolled between March 2003 and March 2004 at the outpatient department of a university hospital referral center for chronic fatigue syndrome patients. Random assignment to 4 weeks treatment with methylphenidate 2 x 10 mg/day, followed by 4 weeks of placebo treatment, or 4 weeks of placebo treatment, followed by methylphenidate treatment. Fatigue and concentration were measured with a Checklist Individual Strength (CIS) and a Visual Analogue Scale (VAS).

RESULTS: Fatigue scores fell significantly during methylphenidate intake in comparison with baseline (mean difference: -0.7, P = .010 for VAS; mean difference: -11.8, P <.0001 for CIS) and in comparison with placebo (mean difference: -1.0, P = .001 for VAS; mean difference: -9.7, P <.0001 for CIS). Concentration disturbances, measured with a VAS improved significantly under methylphenidate treatment compared with baseline (mean difference: -1.3, P <.0001) and compared with placebo (mean difference: -1.1, P <.0001). A clinical significant effect (> or =33% improvement or CIS < or =76) on fatigue was achieved in 17% of patients, who were considered responders; on concentration in 22% of patients.

CONCLUSIONS: Methylphenidate at a dose of 2 x 10 mg/day is significantly better than placebo in relieving fatigue and concentration disturbances in a minority of chronic fatigue syndrome patients. Further studies are needed to investigate the long-term effects of this treatment.

 

Source: Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med. 2006 Feb;119(2):167.e23-30. https://www.ncbi.nlm.nih.gov/pubmed/16443425

 

Effect of physical factors on bioelectric properties of cell nuclei of buccal epithelium in students with chronic fatigue syndrome

Abstract:

60 students with the syndrome of chronic fatigue have been observed in a sanatorium. 35 patients of the main (first) group underwent hydrokinesotherapy. The patients of the second group attended physical exercises as follows: girls attended shaping classes and contrast douche, boys exercised on different training apparatus and took too contrast douche. An estimation of efficiency of the carried out treatment was conducted with the help of clinical and paraclinical methods of the study.

Electrokinetic properties of cellular nuclei of buccalium epithelium were tested to reveal a general nonspecific resistance of the human body. The data of assessment of an electrical potential (Z-potential) showed that clinical improvement coincided with the increase in electrokinetic mobility of cell nucleus of buccalium epithelium (P<0.01). Physical factors proved to have positive influence on homeostas of patients of the main group. This index was not reliable in patients of the second group (P>0.5).

 

Source: Samoĭlovych VA, Hutarieva NV, Tondiĭ LD. Effect of physical factors on bioelectric properties of cell nuclei of buccal epithelium in students with chronic fatigue syndrome. Lik Sprava. 2005 Jul-Sep;(5-6):60-4. [Article in Ukrainian] http://www.ncbi.nlm.nih.gov/pubmed/16396296

 

Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome

Abstract:

OBJECTIVE: To compare effectiveness of oral therapy with reduced nicotinamide adenine dinucleotide (NADH) to conventional modalities of treatment in patients with chronic fatigue syndrome (CFS).

BACKGROUND: CFS is a potentially disabling condition of unknown etiology. Although its clinical presentation is associated to a myriad of symptoms, fatigue is a universal and essential finding for its diagnosis. No therapeutic regimen has proven effective for this condition.

METHODS: A total of 31 patients fulfilling the Centers for Disease Control criteria for CFS, were randomly assigned to either NADH or nutritional supplements and psychological therapy for 24 months. A thorough medical history, physical examination and completion of a questionnaire on the severity of fatigue and other symptoms were performed each trimester of therapy. In addition, all of them underwent evaluation in terms of immunological parameters and viral antibody titers. Statistical analysis was applied to the demographic data, as well as to symptoms scores at baseline and at each trimester of therapy.

RESULTS: The twelve patients who received NADH had a dramatic and statistically significant reduction of the mean symptom score in the first trimester (p < 0.001). However, symptom scores in the subsequent trimesters of therapy were similar in both treatment groups. Elevated IgG and Ig E antibody levels were found in a significant number of patients.

CONCLUSIONS: Observed effectiveness of NADH over conventional treatment in the first trimester of the trial and the trend of improvement of that modality in the subsequent trimesters should be further assessed in a larger patient sample.

 

Source: Santaella ML, Font I, Disdier OM. Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome. P R Health Sci J. 2004 Jun;23(2):89-93. http://www.ncbi.nlm.nih.gov/pubmed/15377055

 

Effect of galantamine hydrobromide in chronic fatigue syndrome: a randomized controlled trial

Abstract:

CONTEXT: There is no established pharmacological treatment for the core symptoms of chronic fatigue syndrome (CFS). Galantamine hydrobromide, an acetyl cholesterone inhibitor, has pharmacological properties that might benefit patients with CFS.

OBJECTIVE: To compare the efficacy and tolerability of galantamine hydrobromide in patients with CFS.

DESIGN, SETTING, AND PATIENTS: Randomized, double-blind trial conducted June 1997 through July 1999 at 35 outpatient centers in the United Kingdom (n = 17), United States (n = 14), the Netherlands (n = 2), Sweden (n = 1), and Belgium (n = 1) involving 434 patients with a clinical diagnosis of CFS (modified US Centers for Disease Control and Prevention criteria).

INTERVENTIONS: A total of 89 patients were randomly assigned to receive 2.5 mg of galantamine hydrobromide; 86 patients, 5.0 mg; 91 patients, 7.5 mg; and 86 patients, 10 mg (these patients received medicine in the tablet form 3 times per day); a total of 82 patients received matching placebo tablets 3 times per day.

MAIN OUTCOME MEASURES: The primary efficacy variable was the global change on the Clinician Global Impression Scale after 4, 8, 12, and 16 weeks of treatment. Secondary outcomes were changes in core symptoms of CFS on the Chalder Fatigue Rating Scale, the Fibromyalgia Impact Questionnaire, and the Pittsburgh Sleep Quality Index; changes in quality of life on the Nottingham Health Profile; and assessment of plasma-free cortisol levels and cognitive performance on a computer-based battery of tests.

RESULTS: After 16 weeks, there were no statistically significant differences between any of the galantamine or placebo groups in clinical condition on the Clinician Global Impression Scale, or for any of the secondary end points. Exploratory regression analysis failed to detect any consistent prognostic factor that might have influenced the primary or any secondary outcome measures.

CONCLUSION: This trial did not demonstrate any benefit of galantamine over placebo in the treatment of patients with CFS.

Comment in:

Pharmacotherapy of chronic fatigue syndrome: another gallant attempt. [JAMA. 2004]

Chronic fatigue syndrome and the cholinergic hypothesis. [JAMA. 2004]

 

Source: Blacker CV, Greenwood DT, Wesnes KA, Wilson R, Woodward C, Howe I, Ali T. Effect of galantamine hydrobromide in chronic fatigue syndrome: a randomized controlled trial. JAMA. 2004 Sep 8;292(10):1195-204. http://www.ncbi.nlm.nih.gov/pubmed/15353532

 

Randomised controlled trial of graded exercise in chronic fatigue syndrome

Abstract:

OBJECTIVE: To investigate whether 12 weeks of graded exercise with pacing would improve specific physiological, psychological and cognitive functions in people with chronic fatigue syndrome (CFS).

DESIGN: Randomised controlled trial.

SETTING: Human performance laboratory at the University of Western Australia.

PARTICIPANTS: 61 patients aged between 16 and 74 years diagnosed with CFS.

INTERVENTIONS: Either graded exercise with pacing (32 patients) or relaxation/flexibility therapy (29 patients) performed twice a day over 12 weeks.

MAIN OUTCOME MEASURES: Changes in any of the physiological, psychological or cognitive variables assessed.

RESULTS: Following the graded exercise intervention, scores were improved for resting systolic blood pressure (P = 0.018), work capacity (W.kg(-1)) (P = 0.019), net blood lactate production (P = 0.036), depression (P = 0.027) and performance on a modified Stroop Colour Word test (P = 0.029). Rating of perceived exertion scores, associated with an exercise test, was lower after graded exercise (P = 0.013). No such changes were observed in the relaxation/flexibility condition, which served as an attention-placebo control.

CONCLUSIONS: Graded exercise was associated with improvements in physical work capacity, as well as in specific psychological and cognitive variables. Improvements may be associated with the abandonment of avoidance behaviours.

Comment in:

To exercise or not to exercise in chronic fatigue syndrome? No longer a question. [Med J Aust. 2004]

To exercise or not to exercise in chronic fatigue syndrome? [Med J Aust. 2004]

 

Source: Wallman KE1, Morton AR, Goodman C, Grove R, Guilfoyle AM. Randomised controlled trial of graded exercise in chronic fatigue syndrome. Med J Aust. 2004 May 3;180(9):444-8. http://www.ncbi.nlm.nih.gov/pubmed/15115421

 

Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome

Abstract:

OBJECTIVES: We compared the effects of acetylcarnitine, propionylcarnitine and both compounds on the symptoms of chronic fatigue syndrome(CFS).

METHODS: In an open, randomized fashion we compared 2 g/d acetyl-L-carnitine, 2 g/d propionyl-L-carnitine, and its combination in 3 groups of 30 CFS patients during 24 weeks. Effects were rated by clinical global impression of change. Secondary endpoints were the Multidimensional Fatigue Inventory, McGill Pain Questionnaire, and the Stroop attention concentration test. Scores were assessed 8 weeks before treatment; at randomization; after 8, 16, and 24 weeks of treatment; and 2 weeks later.

RESULTS: Clinical global impression of change after treatment showed considerable improvement in 59% of the patients in the acetylcarnitine group and 63% in the propionylcarnitine group, but less in the acetylcarnitine plus propionylcarnitine group (37%). Acetylcarnitine significantly improved mental fatigue (p =.015) and propionylcarnitine improved general fatigue (p =.004). Attention concentration improved in all groups, whereas pain complaints did not decrease in any group. Two weeks after treatment, worsening of fatigue was experienced by 52%, 50%, and 37% in the acetylcarnitine, propionylcarnitine, and combined group, respectively. In the acetylcarnitine group, but not in the other groups, the changes in plasma carnitine levels correlated with clinical improvement.

CONCLUSIONS: Acetylcarnitine and propionylcarnitine showed beneficial effect on fatigue and attention concentration. Less improvement was found by the combined treatment. Acetylcarnitine had main effect on mental fatigue and propionylcarnitine on general fatigue.

 

Source: Vermeulen RC, Scholte HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosom Med. 2004 Mar-Apr;66(2):276-82. http://www.ncbi.nlm.nih.gov/pubmed/15039515

 

A randomised, controlled, triple-blind trial of the efficacy of homeopathic treatment for chronic fatigue syndrome

Abstract:

OBJECTIVE: There is no management regime for chronic fatigue syndrome (CFS) that has been found to be universally beneficial and no treatment can be considered a “cure”. Patients with CFS may use complementary and alternative medicine (CAM). Our aim was to evaluate homeopathic treatment in reducing subjective symptoms of CFS.

METHOD: Using a triple-blind design (patient and homeopath blind to group assignment and data analyst blind to group until after initial analyses to reduce the possibility of bias due to data analyst), we randomly assigned patients to homeopathic medicine or identical placebo. One hundred and three patients meeting the Oxford criteria for CFS were recruited from two specialist hospital out patient departments. Patients had monthly consultations with a professional homeopath for 6 months. Main outcome measures were scores on the subscales of the Multidimensional Fatigue Inventory (MFI) and proportions of each group attaining clinically significant improvements on each subscale. Secondary outcome measures were the Fatigue Impact Scale (FIS) and the Functional Limitations Profile (FLP). Ninety-two patients completed treatment in the trial (47 homeopathic treatment, 45 placebo). Eighty-six patients returned fully or partially completed posttreatment outcome measures (41 homeopathic treatment group who completed treatment, 2 homeopathic treatment group who did not complete treatment, 38 placebo group who completed treatment, and 5 placebo group who did not complete treatment).

RESULTS: Seventeen of 103 patients withdrew from treatment or were lost to follow-up. Patients in the homeopathic medicine group showed significantly more improvement on the MFI general fatigue subscale (one of the primary outcome measures) and the FLP physical subscale but not on other subscales. Although group differences were not statistically significant on four out of the five MFI subscales (the primary outcome measures), more people in the homeopathic medicine group showed clinically significant improvement. More people in the homeopathic medicine group showed clinical improvement on all primary outcomes (relative risk=2.75, P=.09).

CONCLUSIONS: There is weak but equivocal evidence that the effects of homeopathic medicine are superior to placebo. Results also suggest that there may be nonspecific benefits from the homeopathic consultation. Further studies are needed to determine whether these differences hold in larger samples.

Comment in: A randomised, controlled, triple-blind trial of the efficacy of homeopathic treatment for chronic fatigue syndrome. [J Psychosom Res. 2004]

 

Source: Weatherley-Jones E, Nicholl JP, Thomas KJ, Parry GJ, McKendrick MW, Green ST, Stanley PJ, Lynch SP. A randomised, controlled, triple-blind trial of the efficacy of homeopathic treatment for chronic fatigue syndrome. J Psychosom Res. 2004 Feb;56(2):189-97. http://www.ncbi.nlm.nih.gov/pubmed/15016577

 

Efficacy of cognitive-behavioural therapy by general practitioners for unexplained fatigue among employees: Randomised controlled trial

Abstract:

BACKGROUND: Fatigue is a common complaint that may lead to long-term sick leave and work disability.

AIMS: To assess the efficacy of cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue among employees.

METHOD: A randomised controlled trial, using a pre-randomisation design in primary care, investigated 151 employees on sick leave with fatigue. Participants in the experimental group were offered five to seven 30 min sessions of cognitive-behavioural therapy by a general practitioner; those in the control group were offered no treatment. Main outcome measures (fatigue severity, self-reported absenteeism, registered absenteeism and clinical recovery) were assessed at 4 months, 8 months and 12 months.

RESULTS: At baseline, 44% of the patients already met research criteria for chronic fatigue syndrome. There was no significant difference between the experimental group and the control group on primary or secondary outcomes at any point.

CONCLUSIONS: Cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue did not prove to be an effective intervention. Since these doctors were unable to deliver this therapy effectively under ideal circumstances, it is unlikely that doctors in routine practice would be more successful in doing so.

 

Source: Huibers MJ, Beurskens AJ, Van Schayck CP, Bazelmans E, Metsemakers JF, Knottnerus JA, Bleijenberg G. Efficacy of cognitive-behavioural therapy by general practitioners for unexplained fatigue among employees: Randomised controlled trial. Br J Psychiatry. 2004 Mar;184:240-6. http://bjp.rcpsych.org/content/184/3/240.long (Full article)

 

Cost-effectiveness of cognitive behaviour therapy for patients with chronic fatigue syndrome

Abstract:

BACKGROUND: There is some evidence that cognitive behaviour therapy (CBT) is efficacious in chronic fatigue syndrome (CFS), but little data on its cost-effectiveness.

DESIGN: Prospective economic analysis alongside a randomized clinical trial.

METHODS: CFS patients were randomly assigned to CBT, guided support groups (SG), or the ‘natural course’ (NC, no protocol-based interventions). Patients were treated for 8 months and followed-up for another 6 months. Costs per patient showing clinically significant improvement, based on the CIS fatigue scale, and costs per quality-adjusted life year, were determined for a time period of 14 months.

RESULTS: Data were available for 171 patients at 8 months and for 128 at 14 months. At 8 and 14 months, the percentages of improved patients were 31% and 27% for CBT, 9% and 11% for SG, and 12% and 20% for NC. Mean QALYs gained at 14 months were, for CBT, SG and NC, respectively, 0.0737, -0.0018 and 0.0458. CBT and SG mean treatment costs were euro1490 and euro424. Other medical costs for CBT, SG, and NC, respectively, were euro324, euro623 and euro412 for the first period, and euro232, euro561 and euro378 for the second period. Non-medical costs for these periods for CBT, SG and NC were euro262, euro550, euro427 and euro226, euro439, euro287, respectively. Productivity costs were considerable, but not significantly different between groups.

DISCUSSION: CBT was less costly and more effective than SG. Compared to NC, the baseline incremental cost-effectiveness of CBT was euro20 516 per CFS patient showing clinically significant improvement, and euro21 375 per QALY. The bootstrap ratios showed considerable uncertainty regarding the results. Future research should focus on productivity costs, and follow patients prospectively over a longer period.

Comment in:

Cost-effectiveness of cognitive behaviour therapy for patients with chronic fatigue syndrome. [QJM. 2004]

Cost-effectiveness of cognitive behaviour therapy for patients with chronic fatigue syndrome. [QJM. 2004]

 

Source: Severens JL, Prins JB, van der Wilt GJ, van der Meer JW, Bleijenberg G. Cost-effectiveness of cognitive behaviour therapy for patients with chronic fatigue syndrome. QJM. 2004 Mar;97(3):153-61. http://qjmed.oxfordjournals.org/content/97/3/153.long (Full article)