Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (ME/CFS) Registry and Biobank, COVID-19, SARS-CoV-2

SARS CoV 2 Infection Clinical Trial

— MECFS-R  

Official title:

Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (ME/CFS) Registry and Biobank

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05778006
• Other study ID #: MECFS-R
• Status: Recruiting
• Start date: May 31, 2022
• Est. completion date: May 31, 2052

Study information

• Verified date: February 2023
• Source: Technical University of Munich
• Contact: Uta Behrends, Prof.
• Phone: +4989 30682632
• Email: uta.behrends[@]tum.de
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Chronic fatigue syndrome (syn. myalgic encephalomyelitis or ME/CFS) is a relatively common, but pathogenetically still insufficiently understood, complex, severe, chronic disease. It has been classified by the WHO as a neurological disorder (ICD-10 G93.3).

The leading symptoms are pathological exhaustion (fatigue) and prolonged, inadequate deterioration of condition after exertion (syn. post-exertional malaise or PEM). In addition, pain, sleep disturbances, flu-like symptoms, and cognitive, autonomic, and neuroendocrine symptoms are typically found.

In the majority of patients*, the trigger is a viral disease, including infectious mononucleosis caused by Epstein-Barr virus (EBV), which is particularly common in young patients, but also influenza or coronavirus disease 2019 (Covid-19) at any age. Causative factors are discussed to be autoimmune mechanisms as well as a genetic predisposition.

The general activity level and quality of life of patients are usually significantly reduced due to the disease. A large proportion of those affected are confined to a wheelchair, home or bed. ME/CFS is one of the most common reasons for long absences from school due to illness.

Because no reliable biomarkers are available, ME/CFS is a diagnosis of exclusion. The diagnosis is made using internationally established clinical criteria and after careful differential diagnosis. To date, no causal, but only symptom-oriented, non-standard treatment approaches are found. With appropriate care, the prognosis in childhood and adolescence is better than in adults. Long-term recovery is possible in two-thirds of young patients, whereas less than one-third of adult patients can expect recovery.

In Germany, there are currently two special outpatient clinics for patients with ME/CFS, one for adult patients* at the Charité Fatigue Centrum in Berlin, headed by Prof. Scheibenbogen, and one for children, adolescents and young adults up to 25 years of age at the ME/CFS focus of the Children's Polyclinic of the MRI of the TUM in Munich, headed by Prof. Behrends. A joint data collection of these ME/CFS centers has not been established.

The proposed ME/CFS registry study (MECFS-R) is intended to initially pool medical data from specialized routine care on a bicenter basis and, after recruitment of additional German centers, on a multicenter, longitudinal, and web-based basis, as extensive as possible, and to make this data available for research.

Following the example of already well-established European registry studies (e.g., the ESID registry of the European Society for Immunodeficiencies), digital data acquisition should take place in a tiered approach according to cost-benefit analysis. Medical institutions can decide, based on capacity, whether a clearly defined core data set (level 1) or more complex data sets (level 2 or 3) should be digitally captured. The digital implementation is to be carried out in collaboration with the Munich-based IT company Bitcare, whose database concepts have proven successful in the context of the Transplantation Cohort (Tx Cohort) of the German Center for Infection Research (DZIF) or the Covid-19 study of the MRI of TUM (COMRI) and with whom the team at the MRI of TUM has been working successfully for many years.

The aim of the MECFS-R is to accurately describe the clinical picture and its course in Germany clinically and epidemiologically as well as to derive epidemiological or medical risk factors, if applicable, and to define subcohorts for future treatment approaches.

Description:

ME/CFS is a complex, severe, chronic disease with an estimated prevalence of approximately 0.3 (0.1-0.5)%1 worldwide. Thus, more people are affected than by multiple sclerosis (MS) or systemic lupus erythematosus (SLE). In Germany, the number of people affected is estimated at approximately 250,000, including 40,000 children and adolescents.2 The patients suffer from pathological exhaustion (fatigue) as well as long-lasting disease aggravation after inadequate low stress (so-called post-exertional malaise, PEM for short). Fatigue and PEM are characteristically accompanied by pain, sleep disturbances, cognitive, autonomic and neuroendocrine symptoms, and flu-like symptoms. In many patients, social participation is severely limited due to the disease. It is not uncommon for considerable absences from training or the workplace to occur, or for patients to be unable to work.3 Often, a febrile episode with proven or suspected viral origin is found at the beginning. When symptomatology is triggered by an infection-like event, it is referred to as "post-infectious" ME/CFS. A prominent trigger of ME/CFS is infectious mononucleosis due to Epstein-Barr virus (EBV-IM), which accounted for approximately half of all post-infectious cases in childhood and adolescence.4-9 In a Chicago study, 6, 12, and 24 months after EBV-IM, 13, 7, and 4%, respectively, of all ill patients showed symptoms of ME/CFS.10 Another recent trigger is disease due to infection with the new SARS coronavirus-2 (SARS-CoV-2), so-called coronavirus disease 2019 (Covid-19). In the growing group of the so-called " Covid-19 long hauler" or those affected by "long Covid-19", an increasing number of affected persons with ME/CFS (so-called post-Covid19-ME/CFS) are found (publication of the Charité in preparation).

The pathophysiology of ME/CFS is still largely unclear and reliable prognostic parameters, biomarkers as well as screening and treatment measures are not available. Due to this fact, active research collaborations on ME/CFS have been established at the U.S. National Institutes of Health (NIH) and in Europe in recent years.11,12 Various immunologic alterations,13-16 evidence of pathogenic autoimmune responses17,18 and molecular genetic biomarker signatures19 have been described.

The diagnosis of ME/CFS (ICD-10 G93.3) is currently made using internationally established clinical criteria and after careful differential diagnosis with exclusion of other causes of fatigue. The case definition is based on the "Canadian criteria" for adults,20 the "Rowe criteria "1 or the "Jason criteria" for children and adolescents.21 In the registry, both definitions will be recorded for ME/CFS in children and adolescents. The diagnostic criteria are based on the compilation and weighting of ME/CFS-typical symptoms.

To date, the few evidence-based treatment options for patients/adolescents with ME/CFS have been exclusively symptom-based. Medication strategies aim at the best possible treatment of pain, sleep and circulatory problems as well as, among others, infections, intestinal dysregulation and/or deficiencies of electrolytes, vitamins or trace elements. Of key importance is counseling on the individual's tolerance to stress or avoidance of PEM ("pacing"), as well as sustained support for psyche, mobility, care, education, and social integration. Correct diagnosis alone can provide significant relief to the patient and family and in this way contribute to recovery. Many patients with missing or incorrect diagnosis are subject to stigma and/or mistreatment.

The Center of Disease Control and Prevention (CDC), the German Society for ME/CFS (DG ME/CFS), the Charité Fatigue Center (CFC), and our own recently founded Elterninitiative ME/CFS-kranke Kinder und Jugendliche München e.V. offer helpful information for affected persons and their treating physicians about the still little-known clinical picture via their websites.22,23,24,25 A written consensus of the European ME/CFS Expert Group (EUROMENE) on diagnosis and treatment of patients with ME/CFS was published as a preprint with our collaboration: https://www.preprints.org/manuscript/202009.0688/v1.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 650
• Est. completion date: May 31, 2052
• Est. primary completion date: May 31, 2052
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• ME/CFS diagnosis (ICD-10 G93.3) based on internationally established criteria

• Informed consent for study participation (by patient and/or guardian(s) of minors).

Exclusion Criteria:

• Lack of diagnosis of ME/CFS (ICD-10 G93.3)

• No informed consent for study participation

Related Conditions & MeSH terms

• COVID-19
• Encephalomyelitis
• Epstein-Barr Virus Infections
• Fatigue
• Fatigue Syndrome, Chronic
• ME/CFS
• Syndrome

Locations

Country	Name	City	State
Germany	München Klinik Schwabing	München

Sponsors (2)

Lead Sponsor	Collaborator
Technical University of Munich	Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phenotyping ME/CFS	Phenotyping ME/CFS through a cross-age, longitudinal collection of epidemiologic, medical, and health care data in a web-based, Germany-wide, multicenter registry study.	30 years
Secondary	Harmonization of the diagnostic process	Harmonization of the diagnostic process	30 years
Secondary	Harmonization of epidemiological and clinical data collection	Harmonization of epidemiological and clinical data collection	30 years
Secondary	Networking of dedicated treatment centers	Networking of dedicated treatment centers	30 years
Secondary	Definition of subcohorts and baseline data for clinical trials	Definition of subcohorts and baseline data for clinical trials	30 years
Secondary	Recording the frequency of comorbidities	Recording the frequency of comorbidities	30 years
Secondary	Estimation of prognosis	Estimation of prognosis	30 years
Secondary	Improving care by training new centers regarding standardized data collection	Improving care by training new centers regarding standardized data collection	30 years
Secondary	Generation of epidemiological, medical and care data (local, national, international) as a basis for innovative care concepts, political measures and public relations.	Generation of epidemiological, medical and care data (local, national, international) as a basis for innovative care concepts, political measures and public relations.	30 years