Tag: randomized controlled trial

Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After COVID-19 or Vaccination: A Randomized Controlled Trial

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can develop as post-vaccination syndrome (PVS) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). In our prior retrospective study, most patients with PVS who developed ME/CFS had vitamin D insufficiency or deficiency. We evaluated the efficacy of vitamin D replacement therapy guidance for ME/CFS symptom improvement in patients with vitamin D insufficiency or deficiency.

Methods: This open-label randomized controlled trial enrolled 91 participants with ME/CFS as PVS or PASC and serum 25(OH) vitamin D < 30 ng/mL across five clinical sites. Participants were randomized 1:1 to intervention (active vitamin D preparation plus vitamin D replacement therapy guidance: 25 μg daily supplementation, dietary counseling, sun exposure, and exercise) or control (active vitamin D preparation alone) for 12 weeks. The primary endpoint was the change in ME/CFS symptom count from screening to Week 12.

Results: Mean symptom change was -6.7 in the intervention group versus -1.2 in the control group (between-group difference -5.6; 95% CI: -7.2, -3.9; p < 0.001). Serum 25(OH) vitamin D improved from 18.6 to 27.1 ng/mL in the intervention group, while the control group showed a decreasing trend (between-group difference 10.2 ng/mL; 95% CI: 7.9, 12.5). Achievement of <8 symptoms (i.e., no longer meeting ME/CFS diagnostic criteria) was significantly higher in the intervention group, with 16 participants achieving this threshold compared to 1 in the control group (p < 0.001). Subgroup analyses showed consistent benefit in both PVS (n = 56) and PASC (n = 29) cohorts.

Conclusions: Vitamin D replacement therapy guidance significantly reduced ME/CFS symptoms along with improvement of serum 25(OH) vitamin D levels in patients with vitamin D insufficiency or deficiency who developed ME/CFS as PVS or PASC.

Source: Kodama S, Nakata M, Konishi N, Yoshino M, Fujisawa A, Naganuma M, Kobayashi Y, Hirai Y, Kitagawa A, Miyokawa M, Mishima R, Teramukai S, Fukushima M. Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After COVID-19 or Vaccination: A Randomized Controlled Trial. Nutrients. 2026 Feb 3;18(3):521. doi: 10.3390/nu18030521. PMID: 41683343. https://www.mdpi.com/2072-6643/18/3/521 (Full text)

Testing the Feasibility of a Self-Help Intervention That Includes Lymphatic Drainage to Reduce Fatigue-Related Symptoms Among Patients with Long COVID in General Practice: Experiences from Our Randomized Controlled Trial (RCT)

Abstract:

Introduction: Long COVID-related fatigue affects a large number of people across the world, with increasing numbers of people experiencing long-term disability as a consequence. We tested the feasibility of a self-help version of a manual osteopathic approach initially developed for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to treat people with long COVID-related fatigue.

Methods: Our feasibility study assessed recruitment into a 1:1 randomized controlled trial (RCT) to receive (i) self-help intervention (self-massage, mobility, flexibility, and breathing exercises, and alternating cold and warm packs to the top of the spine) or (ii) wait-list control group. Follow-up was assessed by online surveys at 3 and 6 months (indicating retention). Verbal feedback was obtained from participants.

Results: Of the 138 eligible survey participants, 126 (90.6%) agreed to participate in two RCTs, achieving the required sample size of 100. Follow-up rates of 79.3% and 59.4% were achieved at 3 and 6 months, respectively. Improvements in Chalder Fatigue Questionnaire (CFQ) scores were observed in both groups between 0 and 3 months (- 4.6 and – 2.9, respectively), to a greater degree in the intervention group (p = 0.01). Feedback showed a cohort keen to engage with the intervention, although some found the intervention onerous at times.

Conclusions: We have reported the results of a feasibility study examining a potentially beneficial intervention for people with long COVID. There were indications of benefit in a patient group with often intractable symptoms. Based on this feasibility study, we believe that the low-cost self-help intervention in isolation could help support fatigue reduction in some people. This has implications for the treatment of both long COVID and ME/CFS.

Source: Riste L, Perrin R, Mulholland T, Hann M, McDonald O, Heald A. Testing the Feasibility of a Self-Help Intervention That Includes Lymphatic Drainage to Reduce Fatigue-Related Symptoms Among Patients with Long COVID in General Practice: Experiences from Our Randomized Controlled Trial (RCT). Infect Dis Ther. 2025 Dec 24. doi: 10.1007/s40121-025-01287-z. Epub ahead of print. PMID: 41442105. https://link.springer.com/article/10.1007/s40121-025-01287-z (Full text)

Acupoint massage at Shenque (CV 8) for chronic fatigue syndrome: a randomized controlled trial

Abstract:

in English, Chinese

Objectives: To observe the clinical efficacy of acupoint massage at Shenque (CV 8) for chronic fatigue syndrome (CFS).

Methods: A total of 71 patients with CFS were randomized into an observation group (36 cases, 2 cases were eliminated, 3 cases dropped out) and a control group (35 cases). Using a specially made massage instrument, acupoint massage was adopted at the the five points of Shenque (CV 8), i.e. the center and the upper, lower, left, and right parts of the inner wall. The manipulation was given 10 min a time, once every 2 days, 3 times a week for 4 weeks continuously. No intervention was delivered in the control group. Before and after treatment, the scores of fatigue scale-14 (FS-14) and Pittsburgh sleep quality index (PSQI) were observed, and the clinical efficacy was evaluated in the both groups.

Results: After treatment, the physical fatigue and mental fatigue scores, as well as the total score of FS-14 were decreased compared with those before treatment in the observation group (P<0.001); the above scores in the observation group were lower than those in the control group (P<0.001). After treatment, excepted for the sleep time and hypnotic scores, the remaining item scores and the total score of PSQI were decreased compared with those before treatment in the observation group (P<0.05); the each item score and the total score of PSQI were lower than those in the control group (P<0.05). The total effective rate in the observation group was superior to that in the control group (P<0.01).

Conclusions: Acupoint massage at Shenque (CV 8) can effectively improve the fatigue state and sleep quality in patients with chronic fatigue syndrome.

Source: Li Z, Ji R, Yan C, Chen Y, Cao Z, Wang J. Acupoint massage at Shenque (CV 8) for chronic fatigue syndrome: a randomized controlled trial. Zhongguo Zhen Jiu. 2023 Jan 12;44(1):67-70. English, Chinese. doi: 10.13703/j.0255-2930.20230307-0002. PMID: 38191162. https://pubmed.ncbi.nlm.nih.gov/38191162/

Characteristics associated with physical functioning and fatigue in patients with chronic fatigue syndrome (CFS): secondary analyses of a randomized controlled trial

Abstract

Objective: This study aimed to explore associations at the group level between patient characteristics at baseline and the outcomes of physical functioning and fatigue in patients with chronic fatigue syndrome (CFS) participating in a randomized controlled trial on cognitive behavioural therapy (CBT).

Methods/design: Consecutively, 236 adult participants fulfilling the Centres for Disease Control and Prevention (CDC) 1994 criteria for CFS were randomly allocated to either 16 weeks of standard CBT, 8 weeks of Interpersonal CBT or a treatment as usual control group. In secondary analyses we investigated how gender, age, pain, anxiety, depression, memory and VO2max at baseline were associated with physical function and fatigue before and after treatment, controlling for the CBT-interventions and the baseline levels of the outcome measures.

For the two groups receiving CBT, a 1-year follow-up analysis was also done. Bivariate and multivariable linear regression was used to explore the targeted associations.

Results: At baseline, less pain (p < .001) and higher VO2max (p = 0.014) were associated with better physical function, while better memory (p = 0.001) and fewer depressive symptoms (p = 0.017) were associated with less fatigue. Better memory and physical function at baseline (p = 0.015 and p < .001, respectively) and male gender (p = 0.003) were associated with higher physical function post-intervention.

Male gender (p = 0.010) was associated with higher physical function at 1-year follow-up. Fatigue severity at baseline was the only variable associated with follow up scores for fatigue (p < .001).

Conclusion: Our findings show that fatigue and physical function were associated with different types of characteristics at baseline, indicating a heterogeneity among CFS patients.

Source: Merethe Eide Gotaas, Tormod Landmark, Anne S. Helvik & Egil A. Fors (2023) Characteristics associated with physical functioning and fatigue in patients with chronic fatigue syndrome (CFS): secondary analyses of a randomized controlled trial, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2023.2175521 https://www.tandfonline.com/doi/full/10.1080/21641846.2023.2175521 (Full text)

Identifying disrupted biological factors and patient-tailored interventions for chronic fatigue in adolescents and young adults with Q-Fever Fatigue Syndrome, Chronic Fatigue Syndrome and Juvenile Idiopathic Arthritis (QFS-study): study protocol for a randomized controlled trial with single-subject experimental case series design

Abstract:

Background: Chronic fatigue with a debilitating effect on daily life is a frequently reported symptom among adolescents and young adults with a history of Q-fever infection (QFS). Persisting fatigue after infection may have a biological origin with psychological and social factors contributing to the disease phenotype. This is consistent with the biopsychosocial framework, which considers fatigue to be the result of a complex interaction between biological, psychological, and social factors. In line, similar manifestations of chronic fatigue are observed in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and juvenile idiopathic arthritis (JIA). Cognitive behavioral therapy is often recommended as treatment for chronic fatigue, considering its effectiveness on the group level. However, not everybody benefits on the individual level. More treatment success at the individual level might be achieved with patient-tailored treatments that incorporate the biopsychosocial framework.

Methods: In addition to biological assessments of blood, stool, saliva, and hair, the QFS-study consists of a randomized controlled trial (RCT) in which a single-subject experimental case series (N=1) design will be implemented using Experience Sampling Methodology in fatigued adolescents and young adults with QFS, CFS/ME, and JIA (aged 12-29). With the RCT design, the effectiveness of patient-tailored PROfeel lifestyle advices will be compared against generic dietary advices in reducing fatigue severity at the group level. Pre-post analyses will be conducted to determine relevance of intervention order. By means of the N=1 design, effectiveness of both advices will be measured at the individual level.

Discussion: The QFS-study is a comprehensive study exploring disrupted biological factors and patient-tailored lifestyle advices as intervention in adolescent and young adults with QFS and similar manifestations of chronic fatigue. Practical or operational issues are expected during the study, but can be overcome through innovative study design, statistical approaches, and recruitment strategies. Ultimately, the study aims to contribute to biological research and (personalized) treatment in QFS and similar manifestations of chronic fatigue.

Trial registration: Trial NL8789 . Registered July 21, 2020.

Source: Vroegindeweij A, Swart JF, Houtveen J, Eijkelkamp N, van de Putte EM, Wulffraat NM, Nijhof SL. Identifying disrupted biological factors and patient-tailored interventions for chronic fatigue in adolescents and young adults with Q-Fever Fatigue Syndrome, Chronic Fatigue Syndrome and Juvenile Idiopathic Arthritis (QFS-study): study protocol for a randomized controlled trial with single-subject experimental case series design. Trials. 2022 Aug 19;23(1):683. doi: 10.1186/s13063-022-06620-2. PMID: 35986408.  https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06620-2 (Full text)

 

Systematic Review of Primary Outcome Measurements for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Randomized Controlled Trials

Abstract:

Background: Due to its unknown etiology, the objective diagnosis and therapeutics of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) are still challenging. Generally, the patient-reported outcome (PRO) is the major strategy driving treatment response because the patient is the most important judge of whether changes are meaningful.

Methods: In order to determine the overall characteristics of the main outcome measurement applied in clinical trials for CFS/ME, we systematically surveyed the literature using two electronic databases, PubMed and the Cochrane Library, throughout June 2020. We analyzed randomized controlled trials (RCTs) for CFS/ME focusing especially on main measurements.

Results: Fifty-two RCTs out of a total 540 searched were selected according to eligibility criteria. Thirty-one RCTs (59.6%) used single primary outcome and others adapted ≥2 kinds of measurements. In total, 15 PRO-derived tools were adapted (50 RCTs; 96.2%) along with two behavioral measurements for adolescents (4 RCTs; 7.7%). The 36-item Short Form Health Survey (SF-36; 16 RCTs), Checklist Individual Strength (CIS; 14 RCTs), and Chalder Fatigue Questionnaire (CFQ; 11 RCTs) were most frequently used as the main outcomes. Since the first RCT in 1996, Clinical Global Impression (CGI) and SF-36 have been dominantly used each in the first and following decade (26.1% and 28.6%, respectively), while both CIS and Multidimensional Fatigue Inventory (MFI) have been the preferred instruments (21.4% each) in recent years (2016 to 2020).

Conclusions: This review comprehensively provides the choice pattern of the assessment tools for interventions in RCTs for CFS/ME. Our data would be helpful practically in the design of clinical studies for CFS/ME-related therapeutic development.

Source: Kim DY, Lee JS, Son CG. Systematic Review of Primary Outcome Measurements for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Randomized Controlled Trials. J Clin Med. 2020 Oct 28;9(11):E3463. doi: 10.3390/jcm9113463. PMID: 33126460. https://pubmed.ncbi.nlm.nih.gov/33126460/

Chronic fatigue syndrome treated by the traditional Chinese procedure abdominal tuina: a randomized controlled clinical trial

Abstract:

OBJECTIVE: To evaluate the effect of the traditional Chinese procedure abdominal Tuina (AT) on chronic fatigue syndrome (CFS).

METHODS: This randomized, single assessor-blinded clinical trial was carried out from May 2014 to April 2015. Eighty participants in the trial were divided randomly into two groups: experimental group and control. The experimental group (40 cases) was treated by AT and the control group (40 cases) by acupuncture. Each treatment was conducted once a day, 5 d for one course, at an interval of 2 d between each course. The whole treatment course lasted for 4 weeks. To ascertain the effect of AT and acupuncture, Fatigue Scale-14 (FS-14), Self-rating Anxiety Scale (SAS) and Hamilton Rating Scale for Depression (HAMD) scores were used before and after treatment. Patients were followed up for 3 months after treatment.

RESULTS: After treatment for 4 weeks, 77 patients (39 cases in the experimental group and 38 cases in the control group) completed the trial. The FS-14, SAS and HAMD scores decreased (P < 0.05) significantly compared with those before treatment in both groups. The FS-14 and HAMD (P < 0.05) scores in the experimental group were much lower than those in the control group. The difference in SAS scores between the two groups was not significant. In the final follow-up, CFS in two cases in the experimental group and three in the control group recurred, but the difference was not significant. The scores for the FS-14, SAS and HAMD in the experimental group were superior to those of the control group, and the difference was significant (P < 0.05). No serious adverse events and few adverse events were observed.

CONCLUSION: AT elicited a more efficacious effect than acupuncture alone on CFS.

Source: Li H, Wang J, Zhang W, Zhao N, Hai X, Sun Q, Sun S, Han Y, Zhang R, Ma F. Chronic fatigue syndrome treated by the traditional Chinese procedure abdominal tuina: a randomized controlled clinical trial. J Tradit Chin Med. 2017 Dec;37(6):819-826. https://www.ncbi.nlm.nih.gov/pubmed/32188192

Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)

Abstract:

BACKGROUND: Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date.

METHODS: RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes.

RESULTS: Among 513 potentially relevant articles, 55 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6316 participants (1568 males and 4748 females, 5859 adults and 457 adolescents). CDC 1994 (Fukuda) criteria were mostly used for case definitions (42 RCTs, 76.4%), and the primary measurement tools included the Checklist Individual Strength (CIS, 36.4%) and the 36-item Short Form health survey (SF-36, 30.9%). Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I):poly(C12U) and CoQ10 + NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility.

CONCLUSIONS: This systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.

Source: Kim DY, Lee JS, Park SY, Kim SJ, Son CG. Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). J Transl Med. 2020 Jan 6;18(1):7. doi: 10.1186/s12967-019-02196-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943902/ (Full article)

Jin’s three-needle acupuncture technique for chronic fatigue syndrome: a study protocol for a multicentre, randomized, controlled trial

Abstract:

BACKGROUND: With an unclear pathomechanism, no confirmed treatment regimen has been established for chronic fatigue syndrome (CFS). Acupuncture is applied as an alternative therapy for CFS. As a kind of acupuncture therapy, Jin’s three-needle acupuncture (JTN) has been applied to treat CFS. However, few large-sample randomised controlled trials on JTN treatment for CFS have been reported. We designed this study to evaluate the efficacy and safety of JTN treatment for CFS.

METHOD/DESIGN: This study is a multicentre, single-blind, randomised controlled trial. Patients who meet the inclusion criteria will be recruited and randomly assigned to either the JTN treatment group or the basic acupuncture group. Both interventions will be conducted for five consecutive days per week and last for 2 weeks. The primary outcome is the effective rate based on the 14-item Fatigue Scale (FS-14) score. Other outcome measures include the Fatigue Assessment Scale (FAI), the Depression Status Inventory (DSI), and the Self-rating Anxiety Scale (SAS). Plasma adrenocorticotropic hormone (ACTH), plasma cortisol, and serum levels of IL-2 and IFN-γ will also be measured in this study. Adverse events will be observed and recorded for the safety evaluation.

DISCUSSION: This study may help to identify the efficacy and safety of JTN acupuncture treatment for CFS.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-IOR-17011009 . Registered on 29 March 2017.

Source: Lin W, Chen XL, Chen Q, Wen J, Chen X. Jin’s three-needle acupuncture technique for chronic fatigue syndrome: a study protocol for a multicentre, randomized, controlled trial. Trials. 2019 Mar 4;20(1):155. doi: 10.1186/s13063-019-3243-5. https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-019-3243-5 (Full article)

Activity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial

Abstract:

OBJECTIVE: To evaluate the effectiveness of an activity pacing self-management (APSM) intervention in improving performance of daily life activities in women with chronic fatigue syndrome (CFS).

METHOD: A total of 33 women with CFS (age 41.1±11.2 yr) were randomly allocated to APSM (experimental group; n=16) or relaxation (control group; n=17). Main outcome measures included the Canadian Occupational Performance Measure (COPM; primary) and Checklist Individual Strength (CIS).

RESULTS: COPM scores changed significantly over time in both groups (p=.03). The change in Satisfaction scores showed a significant difference in favor only of APSM (effect size=0.74 [0.11, 1.4]). CIS scores decreased significantly in the experimental group only (p<.01).

CONCLUSION: APSM was found to be feasible and effective in optimizing participation in desired daily life activities in women with CFS. Replication in a larger sample with long-term follow-up is required.

Copyright © 2015 by the American Occupational Therapy Association, Inc.

 

Source: Kos D, van Eupen I, Meirte J, Van Cauwenbergh D, Moorkens G, Meeus M, Nijs J. Activity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial. Am J Occup Ther. 2015 Sep-Oct;69(5):6905290020. doi: 10.5014/ajot.2015.016287. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564796/ (Full article)