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.

Individual outcomes after tailored versus generic self‐management strategies for persistent fatigue in youth with a fatigue syndrome or rheumatic condition: A multiple single‐case study

“…The current study is part of a larger research effort at the Wilhelmina Children's Hospital, the paediatric hospital of University Medical Center Utrecht (UMC Utrecht) (Vroegindeweij et al, 2022). The research effort focuses on identifying fatigue interventions and disrupted biological factors in AYA with QFS, ME/CFS, PCC and JIA, using a RCT with a multiple single-case design and biological assessments embedded.…”

“…The research effort focuses on identifying fatigue interventions and disrupted biological factors in AYA with QFS, ME/CFS, PCC and JIA, using a RCT with a multiple single-case design and biological assessments embedded. More information can be found in the protocol paper (Vroegindeweij et al, 2022). The current study focuses on the ILD from the multiple single-case design.…”

“…They were screened by a paediatrician at the Wilhelmina Children's Hospital if interested in participation. To be included, participants had to exhibit severe fatigue, defined as a Checklist Individual Strength (CIS)-8 total score of >39 in QFS, PCC and ME/CFS (Vroegindeweij et al, 2022;Worm-Smeitink et al, 2017) and of >34 in JIA (Hewlett et al, 2011;Vroegindeweij et al, 2022) during screening. These inclusion cut-offs are consistent with previous research and indicate similar fatigue levels among these groups (Hewlett et al, 2011).…”

“…Inclusion would be finalized if candidate-participants completed at least 70% of the Experience Sampling Methodology (ESM) diaries during the first four weeks of the study (i.e., part of ILD collection). Exclusion criteria were an acute or chronic infection, inflammatory flare-ups or any concomitant diagnosis that could explain severe fatigue (Vroegindeweij et al, 2022). Ultimately, 60 AYA were included in the RCT in which our multiple single-case design was embedded.…”

“…The AYA from our preceding article were diagnosed with ME/CFS, Q fever Fatigue Syndrome (QFS), post-COVID-19 condition (PCC) or Juvenile Idiopathic Arthritis ( JIA) and participated in a randomized crossover trial (RCT) in which they were assigned to self-management intervention strategies targeting persistent fatigue. This was a lifestyle advice tailored to the participant's biopsychosocial model of fatigue through a method called PROfeel (Nap-van der Vlist, Houtveen, et al, 2021;Vroegindeweij et al, 2022) followed by a generic dietary advice or vice versa (Brink et al, 2019;Vroegindeweij et al, 2022). We expected the tailored PROfeel lifestyle advice to outperform the generic dietary advice due to its tailoring to individual-specific factors.…”