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

• ClinicalTrials.gov Identifier: NCT05778006
• Recruitment Status: Recruiting
• First Posted: March 21, 2023
• Last Update Posted: March 21, 2023
• Sponsor: Technical University of Munich
• Collaborator: Charite University, Berlin, Germany
• Information provided by (Responsible Party): Technical University of Munich

Study Description

Brief 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.

Condition or disease
ME/CFS; SARS CoV 2 Infection; Fatigue Syndrome, Chronic; Epstein-Barr Virus

Detailed 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.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 650 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 30 Years
• Official Title: Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (ME/CFS) Registry and Biobank
• Actual Study Start Date: May 31, 2022
• Estimated Primary Completion Date: May 31, 2052
• Estimated Study Completion Date: May 31, 2052

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Phenotyping ME/CFS [ Time Frame: 30 years ]
   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.

Secondary Outcome Measures :

1. Harmonization of the diagnostic process [ Time Frame: 30 years ]
   Harmonization of the diagnostic process
2. Harmonization of epidemiological and clinical data collection [ Time Frame: 30 years ]
   Harmonization of epidemiological and clinical data collection
3. Networking of dedicated treatment centers [ Time Frame: 30 years ]
   Networking of dedicated treatment centers
4. Definition of subcohorts and baseline data for clinical trials [ Time Frame: 30 years ]
   Definition of subcohorts and baseline data for clinical trials
5. Recording the frequency of comorbidities [ Time Frame: 30 years ]
   Recording the frequency of comorbidities
6. Estimation of prognosis [ Time Frame: 30 years ]
   Estimation of prognosis
7. Improving care by training new centers regarding standardized data collection [ Time Frame: 30 years ]
   Improving care by training new centers regarding standardized data collection
8. Generation of epidemiological, medical and care data (local, national, international) as a basis for innovative care concepts, political measures and public relations. [ Time Frame: 30 years ]
   Generation of epidemiological, medical and care data (local, national, international) as a basis for innovative care concepts, political measures and public relations.

Biospecimen Retention:   None Retained

Serum samples.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

The number of study participants will not be limited. In each case, as many affected persons as possible should be registered nationwide in the long term. In Germany, it is estimated that there are about 250,000 ME/CFS patients (including 40,000 children and adolescents). Currently, the CFC in Berlin treats about 500-600 adult patients per year, the MRI of the TUM about 50 minors and young adults. Increasing numbers of patients are to be covered by increasing the number of staff at the two specialized centers, establishing further centers and establishing cooperation between specialized centers and private practices.

Criteria

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

Contacts and Locations

Contacts

Contact: Uta Behrends, Prof.; +4989 30682632; uta.behrends@tum.de

Contact: Daniela Schindler, Dr.; +4989 41406995; daniela.schindler@tum.de

Locations

Germany

München Klinik Schwabing; Recruiting

München, Germany

Contact: Uta Behrends, Prof. +89 30682632 uta.behrends@tum.de

Sponsors and Collaborators

Technical University of Munich

Charite University, Berlin, Germany

More Information

• Responsible Party: Technical University of Munich
• ClinicalTrials.gov Identifier: NCT05778006
• Other Study ID Numbers: MECFS-R
• First Posted: March 21, 2023
• Last Update Posted: March 21, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Technical University of Munich:

ME/CFS; SARS CoV 2 Infection; Fatigue Syndrome, Chronic; Epstein-Barr Virus

Additional relevant MeSH terms:

COVID-19; Epstein-Barr Virus Infections; Encephalomyelitis; Fatigue Syndrome, Chronic; Syndrome; Fatigue; Disease; Pathologic Processes; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Herpesviridae Infections; DNA Virus Infections; Tumor Virus Infections; Central Nervous System Infections