Category: Clinical Trial

Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up

Abstract:

Chronic fatigue syndrome (CFS) produces physical and neurocognitive disability that significantly affects health-related quality of life (HRQL). Multidisciplinary treatment combining graded exercise therapy (GET) cognitive behavioural therapy (CBT) and pharmacological treatment has shown only short-term improvements.

Aim: To compare the effects on HRQL of (1) multidisciplinary treatment combining CBT, GET, and pharmacological treatment, and (2) usual treatment (exercise counselling and pharmacological treatment) at 12 months of follow-up.

Design: Prospective, randomized controlled trial with a follow-up of 12 months after the end of treatment.

Method: Patients consecutively diagnosed with CFS (Fukuda criteria) were randomly assigned to intervention (n = 60) or usual treatment (n = 60) groups. HRQL was assessed at baseline and 12 months by the Medical Outcomes Study Short-Form questionnaire (SF-36). Secondary outcomes included functional capacity for activities of daily living measured by the Stanford Health Assessment Questionnaire (HAQ) and comorbidities.

Results: At baseline, the two groups were similar, except for lower SF-36 emotional role scores in the intervention group. At 12 months, the intervention did not improve HRQL scores, with worse SF-36 physical function and bodily pain scores in the intervention group.

Conclusion: Multidisciplinary treatment was not superior to usual treatment at 12 months in terms of HRQL. The possible benefits of GET as part of multidisciplinary treatment for CFS should be assessed on an individual patient basis.

 

Source: Núñez M, Fernández-Solà J, Nuñez E, Fernández-Huerta JM, Godás-Sieso T, Gomez-Gil E. Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up. Clin Rheumatol. 2011 Mar;30(3):381-9. doi: 10.1007/s10067-010-1677-y. Epub 2011 Jan 15. https://www.ncbi.nlm.nih.gov/pubmed/21234629

For a list of references see: http://link.springer.com/article/10.1007/s10067-010-1677-y

 

Amisulpride vs. fluoxetine treatment of chronic fatigue syndrome: a pilot study

Abstract:

Different pharmacologic agents have been evaluated in the treatment of Chronic Fatigue Syndrome (CFS), albeit with moderate efficacy. Among the compounds thought to present with potential to be efficacious in CFS patients stands out low-dose amisulpride, a substituted benzamide that has been shown to be an useful treatment for conditions which exhibit some overlap with CFS such as dysthymia and somatoform disorders.

We thus recruited forty non-depressed CFS patients that were randomized to receive either amisulpride 25mg bid, or fluoxetine 20mg uid; all subjects were un-blinded to the treatment regimen. At the time of enrollment in the study and after twelve weeks of treatment, enrolled subjects completed the Krupp Fatigue Severity Scale, the Hospital Anxiety and Depression Scale and a visual analog scale focused on pain and bodily discomfort. Moreover, all subjects were evaluated by a clinician, blinded to the treatment regimen, using the Clinical Global Impression Severity Scale.

Our data revealed a significant improvement both in self-report, and observer-based measures for the amisulpride-treated, but not for the fluoxetine-treated patients. Amisulpride-treated subjects also presented with a significant reduction of somatic complaints, while the amisulpride effect on anxiety and mood levels was not significant. Both drugs were equally well tolerated.

Summing up, we showed a positive symptomatic effect of amisulpride, compared to SSRI treatment, in a group of non-depressed CSF patients on self-report and on observer-based measures of fatigue and somatic complaints. If confirmed by larger, blinded studies, amisulpride thus could represent an effective approach to this difficult-to-treat condition.

Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.

 

Source: Pardini M, Guida S, Primavera A, Krueger F, Cocito L, Gialloreti LE. Amisulpride vs. fluoxetine treatment of chronic fatigue syndrome: a pilot study. Eur Neuropsychopharmacol. 2011 Mar;21(3):282-6. doi: 10.1016/j.euroneuro.2010.10.008. Epub 2010 Nov 26. https://www.ncbi.nlm.nih.gov/pubmed/21112746

 

Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Nicotinamide adenine dinucleotide (NADH) may be depleted in chronic fatigue syndrome (SFC). The purpose of the study was to evaluate the efficacy of supplementation with NADH in these patients.

MATERIAL AND METHODS: A double blind, placebo controlled, 3 month long clinical trial was conducted. The patients were randomized to oral NADH oral 20mg or placebo during the first two months. The intensity of the fatigue, functional performance, mood state, functional impact of the fatigue, quality of life, sleep quality, exercise capacity and functional reserve as well as the investigator’s and patient’s opinion on the efficacy of the intervention prior to and at 30, 60 and 90 days of the onset of the treatment were evaluated. A stress test was performed in the baseline visit and at 60 days (last day of the double blind treatment).

RESULTS: A total of 86 patients, 77 of whom completed the study (mean age, 47 years, 72 women) were enrolled. No significant differences were found in most of the variable studied at the end of the study. Administration of NADH was associated to a decrease in anxiety condition of -1.0 points (p<0.05) and of -0.2 points (p=NS) in the placebo assigned group. Maximum heart rate after the stress test decreased a mean of -8.1l/min (p<0.05) in the NADH group and increased by +1.7l/min in the placebo group (p=0.73). No differences were found in the perception of efficacy with NADH and placebo, by the investigator and patients.

CONCLUSIONS: Administration of oral NADH was associated to a decrease in anxiety and maximum heart rate, after a stress test in patients with CFS. On the contrary, this treatment did not modify other clinical variables and the global functional performance.

 

Source: Alegre J, Rosés JM, Javierre C, Ruiz-Baqués A, Segundo MJ, de Sevilla TF. Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome. Rev Clin Esp. 2010 Jun;210(6):284-8. doi: 10.1016/j.rce.2009.09.015. Epub 2010 May 5. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/20447621

 

Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial

Abstract:

OBJECTIVE: To evaluate the effectiveness of home delivered pragmatic rehabilitation-a programme of gradually increasing activity designed collaboratively by the patient and the therapist-and supportive listening-an approach based on non-directive counselling-for patients in primary care with chronic fatigue syndrome/myalgic encephalomyelitis or encephalitis (CFS/ME).

DESIGN: Single blind, randomised, controlled trial.

SETTING: 186 general practices across the north west of England between February 2005 and May 2007.

PARTICIPANTS: 296 patients aged 18 or over with CFS/ME (median illness duration seven years) diagnosed using the Oxford criteria.

INTERVENTIONS: Participants were randomly allocated to pragmatic rehabilitation, supportive listening, or general practitioner treatment as usual. Both therapies were delivered at home in 10 sessions over 18 weeks by one of three adult specialty general nurses who had received four months’ training, including supervised practice, in each of the interventions. GP treatment as usual was unconstrained except that patients were not to be referred for systematic psychological therapies during the treatment period. Main outcome measures The primary clinical outcomes were fatigue and physical functioning at the end of treatment (20 weeks) and 70 weeks from recruitment compared with GP treatment as usual. Lower fatigue scores and higher physical functioning scores denote better outcomes.

RESULTS: A total of 257 (87%) of the 296 patients who entered the trial were assessed at 70 weeks, the primary outcome point. Analysis was on an intention to treat basis, with robust treatment effects estimated after adjustment for missing data using probability weights. Immediately after treatment (at 20 weeks), patients allocated to pragmatic rehabilitation (n=95) had significantly improved fatigue (effect estimate -1.18, 95% confidence interval -2.18 to -0.18; P=0.021) but not physical functioning (-0.18, 95% CI -5.88 to +5.52; P=0.950) compared with patients allocated to treatment as usual (n=100). At one year after finishing treatment (70 weeks), there were no statistically significant differences in fatigue or physical functioning between patients allocated to pragmatic rehabilitation and those on treatment as usual (-1.00, 95% CI -2.10 to +0.11; P=0.076 and +2.57, 95% CI 3.90 to +9.03; P=0.435). At 20 weeks, patients allocated to supportive listening (n=101) had poorer physical functioning than those allocated to treatment as usual (-7.54, 95% CI -12.76 to -2.33; P=0.005) and no difference in fatigue. At 70 weeks, patients allocated to supportive listening did not differ significantly from those allocated to treatment as usual on either primary outcome.

CONCLUSIONS: For patients with CFS/ME in primary care, pragmatic rehabilitation delivered by trained nurse therapists improves fatigue in the short term compared with unconstrained GP treatment as usual, but the effect is small and not statistically significant at one year follow-up. Supportive listening delivered by trained nurse therapists is not an effective treatment for CFS/ME.

Trial registration International Standard Randomised Controlled Trial Number IRCTN74156610.

Comment in:

Pragmatic rehabilitation for chronic fatigue syndrome. [BMJ. 2010]

Nurse-delivered, home-based pragmatic rehabilitation has a short-term effect on improving fatigue in people with chronic fatigue syndrome compared with usual GP care, but effects were not sustained at 1 year. [Evid Based Nurs. 2010]

 

Source: Wearden AJ, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, Riste L, Richardson G, Lovell K, Dunn G; Fatigue Intervention by Nurses Evaluation (FINE) trial writing group and the FINE trial group and 23 Collaborators. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ. 2010 Apr 23;340:c1777. doi: 10.1136/bmj.c1777. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859122/ (Full article)

 

The effect of ondansetron, a 5-HT3 receptor antagonist, in chronic fatigue syndrome: a randomized controlled trial

Abstract:

BACKGROUND: Accumulating data support the involvement of the serotonin (5-hydroxytryptamine [5-HT]) system in the pathophysiology of chronic fatigue syndrome. Neuropharmacologic studies point to a hyperactive 5-HT system, and open-label treatment studies with 5-HT(3) receptor antagonists have shown promising results. In this randomized controlled clinical trial, the effect of ondansetron, a 5-HT(3) receptor antagonist, was assessed on fatigue severity and functional impairment in adult patients with chronic fatigue syndrome.

METHOD: A randomized, placebo-controlled, double-blind clinical trial was conducted at Radboud University Nijmegen Medical Centre, The Netherlands. Sixty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome and who were free from current psychiatric comorbidity participated in the clinical trial. Participants received either ondansetron 16 mg per day or placebo for 10 weeks. The primary outcome variables were fatigue severity (Checklist Individual Strength fatigue severity subscale [CIS-fatigue]) and functional impairment (Sickness Impact Profile-8 [SIP-8]). The effect of ondansetron was assessed by analysis of covariance. Data were analyzed on an intention-to-treat basis. All patients were recruited between June 2003 and March 2006.

RESULTS: Thirty-three patients were allocated to the ondansetron condition, 34 to the placebo condition. The 2 groups were well matched in terms of age, sex, fatigue severity, functional impairment, and CDC symptoms. Analysis of covariance showed no significant differences between the ondansetron- and placebo-treated groups during the 10-week treatment period in fatigue severity and functional impairment.

CONCLUSIONS: This clinical trial demonstrates no benefit of ondansetron compared to placebo in the treatment of chronic fatigue syndrome.

TRIAL REGISTRATION: www.trialregister.nl: ISRCTN02536681.

©Copyright 2010 Physicians Postgraduate Press, Inc.

 

Source: The GK, Bleijenberg G, Buitelaar JK, van der Meer JW. The effect of ondansetron, a 5-HT3 receptor antagonist, in chronic fatigue syndrome: a randomized controlled trial. J Clin Psychiatry. 2010 May;71(5):528-33. doi: 10.4088/JCP.08m04719whi. Epub 2010 Jan 26. https://www.ncbi.nlm.nih.gov/pubmed/20122367

 

Home orthostatic training in chronic fatigue syndrome–a randomized, placebo-controlled feasibility study

Abstract:

BACKGROUND: Orthostatic (Tilt)-training is an effective treatment for neurally mediated hypotension (NMH). NMH is a frequent finding in chronic fatigue syndrome (CFS). We evaluated home orthostatic training (HOT) in CFS in a randomized placebo-controlled feasibility study.

METHODS: Thirty-eight patients with CFS (Fukuda Criteria) were randomly allocated to daily tilt training (n = 19) or sham training (n = 19) for 6 months. Haemodynamic responses to standing were performed in all subjects using continuous technology (Taskforce) at enrolment, week 1, 4 and 24. Symptom response and compliance were assessed using diaries.

RESULTS: Two patients (one from each arm) withdrew from the study. Fourteen patients in each group complied completely or partially, and patients found the training manageable and achievable. Compared to the sham group, blood pressure while standing dropped to 8.0 mmHg less in the HOT group at 4 weeks (95% CI: 1.0 to 15.0, P = 0.03). At 4 weeks, the HOT group had higher total peripheral resistance compared to the sham group; mean difference 70.2, 95% CI: -371.4 to 511.8. Changes were maintained at 6 months. There was no significant difference in fatigue between groups at 4 weeks (mean difference 1.4, 95% CI: -13.5 to 16.2), but there was a trend towards improvement in fatigue at 6 months. Compliers had lower fatigue compared to non-compliers.

CONCLUSIONS: A placebo-controlled study of HOT in CFS is feasible. HOT is well tolerated and generally complied with. A likely physiological rationale for HOT in CFS is related to reductions in orthostatic intolerance. An adequately powered study including strategies to enhance compliance is warranted.

 

Source: Sutcliffe K, Gray J, Tan MP, Pairman J, Wilton K, Parry SW, Newton JL. Home orthostatic training in chronic fatigue syndrome–a randomized, placebo-controlled feasibility study. Eur J Clin Invest. 2010 Jan;40(1):18-24. doi: 10.1111/j.1365-2362.2009.02225.x. Epub 2009 Nov 12. https://www.ncbi.nlm.nih.gov/pubmed/19912315

 

Randomized controlled study on influence of acupuncture for life quality of patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To observe effects of acupuncture on quality of life of patients with chronic fatigue syndrome (CFS).

METHODS: Randomized, controlled and single-blinded study method was used, 70 cases were divided into an observation group and a control group, 35 cases in each group. The observation group was treated with acupuncture at Baihui (GV 20), Danzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Guanyuan (CV 4), Hegu (LI 4), Zusanli (ST 36), etc.; the control group was treated with acupuncture at non-meridian points (2 cm to the acupoints), thrice a week. The treatment was given for 14 times. The World Health Organization Quality of Life (WHOQOL-BREF) scale was used to evaluate the patients’ quality of life before and after treatment.

RESULTS: The physiological field, individuals own perception of his health condition and total score were significantly improved after treatment in the observation group (all P<0.05); there were no obvious changes in the psychology, social relationships, environment and subjective feelings about the quality of life (all P>0.05). The score of the environmental field in the control group was significantly decreased compared to that before treatment (P<0.05), and there were no significant changes in the other scores. There were no adverse effects in patients.

CONCLUSION: Acupuncture can improve the quality of life of CFS patients, especially in physiological field and the individual perception to his well being. Acupuncture has high safety, and the acupoints has high specific degree than non-meridian points.

 

Source: Wang JJ, Song YJ, Wu ZC, Chu XO, Wang QM, Wei LN, Wang XJ, Meng H. Randomized controlled study on influence of acupuncture for life quality of patients with chronic fatigue syndrome. Zhongguo Zhen Jiu. 2009 Oct;29(10):780-4. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/19873911

 

Effect of lixu jieyu recipe in treating 75 patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To investigate the effective Chinese medicine treatment of chronic fatigue syndrome (CFS).

METHODS: Seventy-five CFS patients meeting the inclusive criteria were enrolled from March 2007 to April 2008 and randomized into two groups. The 40 patients in the treated group were orally treated with Lixu Jieyu Recipe (LJR, consisted of milkvetch root 30 g, kudzuvine root 30 g, asiabell root 15 g, red sage root 10 g, aizoon stonecrop 15 g, epimeddium herb 10 g, curcuma root 10 g, and grassleaved sweetflag rhizome 10 g, made into 200 mL of decoction), for 100 mL twice a day. The 35 patients in the control group were treated with vitamin B tablets (10 mg twice a day), adenosine triphosphate (ATP, 20 mg, thrice a day) and Oryzanol tablets (20 mg thrice a day). The laboratory indicators including serum immunoglobulins (IgG, IgA, IgM, IgE), blood immune cells, as T-cells (Th and Ts), B-cells, natural killer cells, as well as CD4/CD8 ratio were measured before and after 3-month treatment.

RESULTS: After treatment the difference in scores of fatigue symptoms between the two groups was significant (P < 0.01), the scores of various SCL-90 factors and the total score significantly reduced in the treated group after treatment (P < 0.01). Levels of the immunoglobulins measured before treatment were in an equilibrium state, they all were unchanged after treatment in both groups (P > 0.05), and showed no significant difference between groups either before or after treatment. As for the immune cells, significant increase of the lowered Th, Ts cells, and decrease of CD4/CD8 ratio were found in both groups after treatment (P < 0.05), but the improvement was more significant in the treated group, so the difference between groups in these indices after treatment also showed statistical significance (P < 0.05).

CONCLUSION: LJR shows superiority in treating CFS.

 

Source: Zhang ZX, Wu LL, Chen M. Effect of lixu jieyu recipe in treating 75 patients with chronic fatigue syndrome. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2009 Jun;29(6):501-5. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/19702080

 

Randomized controlled clinical trials of acupuncture treatment of chronic fatigue syndrome

Abstract:

OBJECTIVE: To observe the effect of acupuncture on the fatigue degree in patients with chronic fatigue syndrome (CFS).

METHODS: Seventy CFS patients were equally randomized into control and treatment groups according to randomized block design. Acupuncture was applied to Baihui (GV 20), Danzhong (CV 17), Zhongwan (CV 12), etc., for patients in treatment group, and to non-acupoints (2 cm respectively to the abovementioned acupoints) for those in control group. The treatment was given once every other day, 14 times altogether. The fatigue degree and the therapeutic effect were assessed by Chalder’s fatigue scale (FS).

RESULTS: A total of 64 cases (32/group) were finished in this study. After the treatment, the physical FS (5.0 +/- 2.4 vs 6.8 +/- 1.5), mental FS (1.8 +/-1.8 vs 3.1 +/- 1.5) and the total FS (6.8 +/- 3.8 vs 9.9 +/- 2.5) in treatment group, physical FS (5.0 +/- 2.5 vs 6.4 +/- 1.5) and the total FS (7.5 +/- 3.4 vs 9.6 +/- 2.8) in control group decreased significantly compared with pre-treatment (P < 0.01, P < 0.05). There was no marked change in mental FS (2.5 +/- 11.6 vs 3.2 +/- 11.6) in control group after the treatment (P > 0.05). Comparison between two groups showed no significant differences in the 3 indexes (P > 0.05).

CONCLUSION: Acupuncture can relieve CFS patients’ physical and mental fatigue and the therapeutic effect of acupuncture of acupoints is relatively better than that of non-acupoints in reducing mental fatigue.

 

Source: Wang JJ, Song YJ, Wu ZC, Chu XO, Wang QM, Wang XJ, Wei LN, Meng H, Wang XH. Randomized controlled clinical trials of acupuncture treatment of chronic fatigue syndrome. Zhen Ci Yan Jiu. 2009 Apr;34(2):120-4. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/19685727

 

A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is complex illness of unknown etiology. Among the broad range of symptoms, many patients report disturbances in the emotional realm, the most frequent of which is anxiety. Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora. Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans.

In this pilot study, 39 CFS patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two months. Patients provided stool samples and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention. We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01). These results lend further support to the presence of a gut-brain interface, one that may be mediated by microbes that reside or pass through the intestinal tract.

 

Source: Rao AV, Bested AC, Beaulne TM, Katzman MA, Iorio C, Berardi JM, Logan AC. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6. doi: 10.1186/1757-4749-1-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664325/ (Full article)