The primary objective is to identify clinical and biological measures that discriminate paediatric ME/CFS and post-COVID patients from healthy controls based on either clinical (based on physiological tests and questionnaires) and biological (based…
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Brief title
Condition
- Muscle disorders
- Central nervous system infections and inflammations
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
For our primary endpoint we will clinically (questionnaires and physiological
tests; e.g. fatigue) and biologically characterise patients and controls. For
biological characterisation we will focus on determining blood proteome (with
multiplex assays we will determine ~200 proteins) and blood metabolome
(untargeted direct-infusion high-resolution mass spectrometry, >1800
metabolites, on blood and isolated immune cells followed by validation through
targeted LC-MS/MS based metabolomics, depending on the initial findings) to
identify factors that can discriminate paediatric ME/CFS and post-COVID from
healthy controls or identify subgroups within the patient group.
For clinical characterisation we will focus on:
• The ME/CFS criteria. Several criteria exist to diagnose children with ME/CFS.
These criteria differ in stringency. To participate in this study, all patients
must meet the CDC-94 criteria. To characterise patients further, we will check
whether patients also meet the CCC and ICC criteria for ME/CFS. To see the
differences between the three criteria, we refer to the table below. Doctor
reports from standard care and DSQ questionnaires will be used to check whether
patients meet all criteria.
• Self-reported data at inclusion (demographic, behavioural, symptoms,
clinical, and fatigue/pain) at inclusion, repeated 6 and 12 months after
inclusion. For more information, see METC protocol 24/217.
Secondary outcome
We will determine:
• Hair cortisol
• Oral microbiota composition
• Immune cell transcriptome: RNA sequencing
• Dynamic change in metabolism (fluxomics)
• Derangements in mitochondrial functions in immune cells (e.g. mitophagy,
mitochondrial membrane potential, fission and fusion, and superoxide production
• Rest material of biologicals will be stored in a biobank for 15 years. This
biobank is the central biobank of the UMCU and is located in the Wilhelmina
Children*s Hospital. This biobank will be created to facilitate (future)
research on ME/CFS, post-COVID and other immune diseases. Biomaterials can be
requested by our consortium members for research purposes if participants gave
informed consent for research related to chronic fatigue and other immune or
metabolic diseases.
• Other study parameters/endpoints: Researchers from the national effort (the
Netherlands ME/CFS Cohort and Biobank, NMCB, consortium and Post-COVID Network
Netherlands, PCNN) funded by ZonMw may request data from our cohort for their
research purposes or to collaborate with us. These specific research questions
remain to be determined and will also depend on the research now done in
adults.
Background summary
Rationale: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a
debilitating disease that currently still lacks a universally accepted cause,
diagnosis, or treatment. Manifestations of ME/CFS can develop for example after
infection with Q fever, Epstein-Barr, or SARS-COV-19, where it is also called
post-COVID. Often, the infectious trigger of ME/CFS remains unidentified.
Recently, a large national effort has been established to build an adult cohort
of patients with ME/CFS symptoms (plus healthy controls) and post-COVID. This
cohort aims to unravel biomedical aspects of ME/CFS and post-COVID in order to
improve our understanding and treatment of the disease. A paediatric cohort is
missing in the national effort - but given that paediatric ME/CFS and
post-COVID present themself differently than adult - an understanding of ME/CFS
*across the lifespan* is essential to provide the best possible treatment at
any age. The necessity of building and studying a paediatric cohort is
underlined by studies showing that 1) ME/CFS symptoms are related to lower
quality of life and decreased school attendance; 2) one out of five paediatric
patients still have debilitating symptoms one year after diagnosis; and 3)
longer disease duration is related to lower effectiveness of
non-pharmacological treatment as usual.
Study objective
The primary objective is to identify clinical and biological measures that
discriminate paediatric ME/CFS and post-COVID patients from healthy controls
based on either clinical (based on physiological tests and questionnaires) and
biological (based on biomaterials) data, or a combination thereof.
Secondary objectives are to assess whether specific immunological, microbiome,
cardiovascular, and/or hormonal disturbances are associated with specific
symptoms and whether these measures have predictive and/or prognostic value.
Additionally, a ME/CFS and post-COVID biobank will be built by storing
collected biomaterials in the UMCU biobank. This biobank will facilitate
paediatric ME/CFS and post-COVID research as well as research into other immune
and metabolic diseases.
Study design
Study design: Observational study collecting data from questionnaires, physical
measurements, and biomaterials (blood, hair, oral swab). Follow-up visit after
6 months to collect new biomaterials, follow-up questionnaires at 6 months and
12 months.
Study burden and risks
Burden and benefits: Burden will be minimised by taking data from standard care
questionnaires (PROactive) and combining blood drawn from standard care with
research. Additional research activities (three additional questionnaires,
physiological measurements, and collection of hair and oral swab) will take
place during one study visit at the 030-lab (max. 1,5 hours). For participants,
the collection of data from questionnaires, physiological measurements, and
biomaterials (blood, hair, oral swab) will have negligible risks. Patients
might experience PEM or fatigue after the physiological tests, which might in
some cases cause (temporary) worsening of symptoms. To minimise the burden on
patients, a separate room will be made available in the 030-lab to give
patients the opportunity to rest between the tests.
Participants will have no direct benefit of participating in this cohort, but
they will contribute to our understanding of ME/CFS symptoms.
UMC Utrecht, Lundlaan 6
Utrecht 3584EA
NL
UMC Utrecht, Lundlaan 6
Utrecht 3584EA
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria for patients: For eligibility, patients must meet the
following criteria:
- Age of 8-18 years old;
- Able to speak, read, understand, and write Dutch;
- ME/CFS patients: A (suspected) diagnosis of ME/CFS according to the CCC and
severely fatigued, as indicated by a fatigue severity score of >= 21 on the
Checklist
Individual Strength-4 (CIS-4) questionnaire.
- Post-COVID patients: a (suspected) diagnosis of post-COVID according to the
WHO definition. Patients should have positive COVID-19 serology and should
express that their symptoms started after acute COVID-19 infection. CCC will be
monitored.
Inclusion criteria for healthy controls: For eligibility, healthy controls must
meet the
following criteria:
- Age of 8-18 years old;
- Able to speak, read, understand, and write Dutch;
- No ME/CFS diagnosis according to the CDC, CCC and ICC;
- No post-COVID condition or other manifestation of persistent fatigue and/or
pain;
- Not severely fatigued, as indicated by a fatigue severity score of <21 on the
CIS-4
questionnaire.
Exclusion criteria
Exclusion criteria: Potential subjects who meet any of the following criteria
will be excluded from participation in this cohort:
Having any concomitant diagnoses that may explain the fatigue (also including
predominated psychiatric comorbidity such as major depression disorder,
generalised anxiety disorder, presence of suicidal risk, etc.).
Being on therapeutic anticoagulant treatment (with an exception for
acetylsalicylic acid, dipyridamole) or having a high risk of bleeding due to a
coagulation disorder.
Having cognitive impairment (with an estimated IQ of < 70).
Having morbid obesity.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL86852.041.24 |