A Longitudinal Study on Longstanding Complicated Fatigue

Covid19 Clinical Trial

Official title:

A Longitudinal Study on Longstanding Complicated Fatigue: Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS), Burnout Syndrome and Post-covid Fatigue

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04955587
• Other study ID #: EPN2018/1438-31
• Status: Recruiting
• Start date: August 24, 2021
• Est. completion date: August 2025

Study information

• Verified date: April 2023
• Source: Stockholm University
• Contact: Anna Andreasson, A Prof
• Phone: +46731505653
• Email: anna.andreasson[@]su.se
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of the study is to investigate if there are common biopsychosocial vulnerability factors for developing and maintaining fatigue, regardless of the diagnosis. The investigators also believe that subgroups differ in terms of these factors. Participating patients with ME/CFS, burnout syndrome and post-covid fatigue complete a web form at inclusion and after 1, 2, 4, 6, 12, 18 and 24 months. There is no upper limit for the number of participants in the web survey. 150 participants are asked to submit blood samples at a local laboratory in connection with the questionnaires for analysis of inflammatory markers and one urine sample for analysis of nutritional markers. Two control groups are included, 150 patients with rheumatoid arthritis and 50 healthy individuals. The longitudinal design makes it possible to investigate how inflammatory markers, nutritional status, symptom burden, health related quality of life co-vary over time and how work ability and sick leave is affected.

Description:

Fatigue is associated with impaired health and severely impaired quality of life and function and there is a need to explore similarities and differences regarding biopsychosocial vulnerability and maintenance factors and consequences in terms of work ability and sick leave in chronic fatigue syndrome (ME / CFS), burnout syndrome (BS) and post-covid fatigue to be able to improve individualized interventions for patient with persistent fatigue. The study examines inflammatory markers, nutritional status, symptom burden, neuropsychiatric conditions, work ability, and sick leave in a longitudinal cohort study over 2 years in patients with different diagnoses who all suffer from persistent fatigue. The hypothesis is that there are common biopsychosocial vulnerability factors for developing and maintaining fatigue, regardless of the diagnosis. The investigators also believe that subgroups can be identified that differ in terms of these factors. The longitudinal design makes it possible to investigate how inflammatory markers, nutritional status, symptom burden, health related quality of life co-vary over time and how work ability and sick leave is affected.

In this study participating patients with ME/CFS, BS and post-covid fatigue complete a web form at inclusion and after 1, 2, 4, 6, 12, 18 and 24 months.

Adult patients registered with a diagnosis of chronic complicated fatigue (ME/CFS or post-covid syndrome) in Take Care (medical record system in Stockholm County, Sweden) or with burnout syndrome from Stressmottagningen Stockholm, will be asked to participate in the study.

• Patients with ME/CFS will be recruited at the Department of Behavior Medicine, Karolinska University Hospital Solna or reached by advertising on social media

• Patients with Post-covid-syndrome will be recruited at Karolinska University Hospital or reached by advertising on social media

• Patients with burnout syndrome will be recruited at Stressmottagningen Stockholm

At baseline, a clinical assessment is performed at the clinic and the patient is asked to leave a venous blood sample and complete a questionnaire. The patients are asked for further blood samples and questionnaires at 1, 2, 4, 6, 12, 18, and 24 months after baseline. 150 participants, 50 in each diagnostic group, are asked to submit blood samples for biobanking at a local laboratory in connection to the questionnaire time points for analysis of inflammatory markers. C-reactive protein (CRP) is analysed at the time of blood samples. They are also asked to give one urine sample for analysis of nutritional markers and to submit a 3-day diet diary for evaluation of dietary intake by a registered dietitian. Participants that only fill out the web-based questionnaire will be included. There is no upper limit for the number of participants in the web survey.

A pilot study with 20 participants with ME/CFS started in 2018 to test and revise the design of the present study. These subjects will be counted in the group of 50 participants with ME/CFS diagnosis when available data allow.

In addition to the participants with persistent fatigue, two control groups are included in the study. 150 patients with rheumatoid arthritis (RA) recruited from the Karolinska University Hospital Rheumatology department and 50 healthy controls. The RA controls fill out the illness generic questionnaires on paper and disease information is taken from the national registry for rheumatic disease and CRP and erythrocyte sedimentation rate (ESR) data is taken from the medical record. The healthy controls follow the same procedure as the patients with persistent fatigue but only fill out the form and give blood samples at one time point.

Research questions:

• Are there differences in patient reported fatigue dimensions, symptom burden including post exertional malaise, sleep disorders, health related quality of life, or inflammatory markers, nutritional markers and dietary intake, between patients with ME/CFS, BS and post-covid fatigue, patients with RA and healthy controls?

• Are inflammatory markers and nutritional status associated with the development/recovery of fatigue and symptom burden in ME/CFS, BS and post-covid fatigue?

• Can different subtypes of patients be identified based on latent factor analysis including fatigue dimensions, symptom profile, neuropsychiatric symptoms, inflammatory markers and nutritional status?

• How does inflammatory markers, nutritional status, symptom burden and health related quality of life influence work ability and sick leave in patients with persistent fatigue over time?

The project group consists of a multidisciplinary team from Stockholm and Linköping universities as well as clinically active at clinics in the two regions who often meet patients with persistent fatigue.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: August 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis set within Stockholm County of ME/CFS, burnout syndrome or post-COVID-19-syndrome according to the Swedish version of the international classification of disease (ICD)-10

• Control group (rheumatic disease): Diagnosis of rheumatoid arthritis

• Control group (healthy): no diagnosis related to inflammatory disease or fatigue

Exclusion Criteria:

• Organic or neuropsychiatric disease that explain the fatigue among cases diagnosed with ME/CFS, burnout syndrome or post-COVID-19-syndrome according to the Swedish ICD-10

Related Conditions & MeSH terms

• Burnout
• Burnout, Psychological
• Chronic Fatigue Syndrome
• Covid19
• Fatigue
• Fatigue Syndrome, Chronic
• Syndrome

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital Solna, dep medical psychology	Stockholm

Sponsors (4)

Lead Sponsor	Collaborator
Stockholm University	Karolinska Institutet, Karolinska University Hospital, Linkoeping University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Attention deficit hyperactivity disorder (ADHD)	Adult ADHD self-report scale (ASRS). ASRS consists of 18 questions in two parts rated on a 5-point scale where a higher score corresponds to a higher symptom burden. Possible range 0-72 points.	baseline
Other	Burnout	Shirom-Melamed Burnout Questionnaire (SMBQ)-22 consists of 22 items rated on a 7-point rating scale where a higher total score corresponds to a higher symptom level (range 22-145).	baseline
Other	Perfectionism	Clinical Perfectionism Questionnaire (CPQ) consists of 12 statements rated on a 4-point Likert scale (range total score 4-48), a higher score corresponds to a higher rate of perfectionism	baseline
Other	Attention spectrum disorder (ASD)	Ritvo Autism and Asperger Diagnostic Scale (RAADS)-14 consists of 14 statements rated on a 4-point scale with a total score ranging from 0-42, with a higher score corresponding to more severe symptoms.	baseline
Other	Presence of hypermobility	Participants complete the 5 PQ questionnaire for hypermobility at one time point. The questionnaire includes 5 items answered Yes/no, where 2 or more affirmations are indicative of hypermobility.	baseline
Primary	Change in fatigue (Multidimensional Fatigue Inventory)	The Multidimensional Fatigue Inventory (MFI)-20 assesses five dimensions of fatigue. MFI-20 has an even proportion of positively and negatively worded items that are rated on a 5-point Likert scale. Subscale scores (range 4-20) are calculated as the sum of item ratings and a total fatigue score (range 20-100) is calculated as the sum of subscale scores. Higher scores indicate a higher level of fatigue. The participants completes the MFI at baseline and after 1, 2, 4, 6, 12, 18 and 24 months.	baseline and 1, 2, 4, 6, 12, 18 and 24 months
Primary	Change in symptom burden	Symptom burden is assessed with a checklist and severity rating of the symptoms in the Canada criteria for ME/CFS. The checklist consists of 25 symptoms rated as present/non present. Severity of present symptoms are rated on a 4-point scale. The total score of 0-125 points with a higher score corresponding to a higher symptom burden. The participants completes this form at baseline and after 1, 2, 4, 6, 12, 18 and 24 months.	baseline and 1, 2, 4, 6, 12, 18 and 24 months
Primary	Change in Generalized sickness behavior (Sickness questionnaire)	The sickness questionnaire assesses symptoms of sickness behavior. 10 items are rated on a 4-point Likert scale, total score ranges from 0-30, the higher the scores the more symptoms. The participants completes the the Sickness questionnaire at baseline and after 1, 2, 4, 6, 12, 18 and 24 months.	baseline and 1, 2, 4, 6, 12, 18 and 24 months
Primary	Change in health related quality of life (World health organization disability assessment scale)	The 12-item scale is summarized to a score of 0-100 and a higher score represents a worse quality of life/functioning. The participants completes WHO disability assessment scale (WHODAS) 2.0 at baseline and after 1, 2, 4, 6, 12, 18 and 24 months.	baseline and 1, 2, 4, 6, 12, 18 and 24 months
Primary	Change in Inflammatory markers	Inflammatory markers will be analysed in collaboration with Linköping University at the end of the study. State of the art methods available at study completion will be used. The participants donate blood sample at baseline and after 1, 2, 4, 6, 12, 18 and 24 months. C-reactive protein is analyzed at the time of blood sampling.	baseline and 1, 2, 4, 6, 12, 18 and 24 months
Primary	Dietary intake	The participants complete 3 day diet diaries at month 6 that are analysed by a registered dietitian.	6 months
Primary	Nutritional status	The participants take the Organix Basic test by Nordic Laboratories at month six.	6 months
Primary	Change in self-reported work ability	The participants report their sick leave (in %, higher % higher sick leave) and work ability (in percent, higher percent higher work ability) at baseline and after 1, 2, 4, 6, 12, 18 and 24 months	baseline and 1, 2, 4, 6, 12, 18 and 24 months
Secondary	Change in insomnia score (insomnia severity index)	Insomnia severity index (ISI) is completed at baseline and after 1, 2, 4, 6, 12, 18 and 24 months. ISI consists of 7 items with a total score ranging from 0 to 28 points, where a higher score corresponds to worse symptoms.	baseline and 1, 2, 4, 6, 12, 18 and 24 months
Secondary	Gastrointestinal symptom burden (gastrointestinal symptom rating scale)	The participant completes the gastrointestinal symptom rating scale (GSRS-IBS) at 6 and 18 months. The GSRS-IBS includes 13 items that measure the severity of IBS symptoms in five clusters (pain, bloating, constipation, diarrhea, and early satiety) during the last seven days. The items are scored between 1 and 7, where 1 corresponds to "no discomfort at all" and 7 to "very severe discomfort" from the symptom. Total score ranges from 13 to 91, with a higher score corresponding to a higher symptom burden.	6 and 18 months