Clinical trial NCT05017142: Swiss Pediatric Inflammatory Brain Disease Registry (Swiss-Ped-IBrainD)
Official title: Swiss Pediatric Inflammatory Bain Disease Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Optic Neuritis
Transverse Myelitis
Acute Disseminated Encephalomyelitis
Multiple Sclerosis
Neuromyelitis Optica Spectrum Disorder
Anti-NMDAR Encephalitis
Anti-GAD65 Associated Autoimmune Encephalitis
Anti-AMPAR-1/2 Associated Autoimmune Encephalitis
Anti-Lgi-1 Associated Autoimmune Encephalitis
Anti-CASPR-2 Associated Autoimmune Encephalitis
Anti-GABAR-1/2 Associated Autoimmune Encephalitis
Onconeuronal Antibody (Hu, Ri, Yo, Amphiphysin, CRMP-5, Ma-1, Ma-2, SOX-1) Associated Autoimmune Encephalitis
Hashimoto Encephalitis
CNS Vasculitis
CNS Sarcoidosis
CNS Lupus
Rasmussen Encephalitis
Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)
Lead sponsor: University of Bern
Sponsor class: OTHER
Collaborators: name: Schweizerische Multiple Sklerose Gesellschaft
name: Insel Gruppe AG, University Hospital Bern
name: Novartis
name: Anna Mueller Grocholski-Stiftung
name: Gottfried und Julia Bangerter- Rhyner-Stiftung, Basel
name: Biogen
name: Roche Pharma (Switzerland) Ltd
name: Fondation Johanna Dürmüller-Bol
name: Kantonsspital Aarau
name: University Children's Hospital Basel
name: Ente Ospedaliero Cantonale, Bellinzona
name: Kantonsspital Graubünden
name: University Hospital, Geneva
name: Centre Hospitalier Universitaire Vaudois
name: Ostschweizer Kinderspital
name: Kantonsspital Winterthur KSW
name: Sanofi
name: Hôpital Fribourgeois
name: University Children's Hospital, Zurich
name: Luzerner Kantonsspital
First posted: 2021-08-23
Enrollment: 500
Sex: ALL
Maximum age (years): 36
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: All patients living and/or treated in Switzerland with a listed IBrainD diagnosed from 2005 onward and a disease onset before the age of 18.

Brief summary: The Swiss-Ped-IBrainD is a national patient registry that collects information on diagnosis, symptoms, treatment, and follow-up of pediatric patients with an inflammatory brain disease in Switzerland. It was first implemented in 2020 in the pediatric clinic of the university hospital in Bern. Further centers all over Switzerland opened for recruitment after that: Aarau, Basel, Bellinzona, Chur, Geneva, Lausanne, Lucerne, St. Gallen, Winterthur and Zurich. The center in Fribourg is expected open for recruitment in 2025. The registry provides data for national and international monitoring and research. It supports research on inflammatory brain diseases in Switzerland and the exchange of knowledge between clinicians, researchers, and therapists. The registry aims to improve the treatment of children with inflammatory brain diseases and optimizing their health care and quality of life.

Detailed description: Background:

Pediatric onset MS and other inflammatory brain diseases (IBrainDs) are severe diseases affecting children and adolescents in a period of essential brain development. This possibly leads to a variety of focal neurological deficits as well as early cognitive impairment. In turn, the cognitive impairment may impact school performance and vocational achievements.

Timely diagnosis and treatment initiation as well as individually tailored management are important for a favorable disease course. However, the diagnosis of the different IBrainDs can be challenging, especially in young children, since their first acute inflammation is often accompanied by unspecific symptoms common to all IBrainDs. A systematic assessment of similarities and differences between clinical signs, symptoms, and diagnostic workup of different IBrainDs will enable faster and more reliable diagnosis.

Furthermore, neither epidemiological data nor information on health care management and disease outcome of pediatric IBrainD patients exist in Switzerland. Therefore, a national registry is being established, which will allow a deeper understanding of pediatric IBrainD epidemiology, clinical presentation, and management. Ultimately, the registry will improve the care of children suffering from an IBrainD in Switzerland.

The Swiss-Ped-IBrainD Registry (title: "Swiss Pediatric Inflammatory Brain Disease Cohort Study", project number: 2019-00377) has been approved by the ethics committees of Bern, the Ethikkommission Nordwest- und Zentralschweiz (EKNZ), the Ethikkommission Ostschweiz (EKOS), and the ethics committees of Zürich, Lausanne, Geneva, and Bellinzona.

Objectives:

The registry pursues the following goals:

1. Gathering representative, population-based epidemiological data on pediatric IBrainD in Switzerland.
2. Monitoring treatment, clinical course, education, social aspects, and outcomes of pediatric IBrainD patients.
3. Providing a platform to facilitate research, national and international collaboration and exchange of knowledge between experts.

The registry thus addresses the increasing requests for medical trial participation and promotes the exchange with existing adult registries (e.g., Swiss MS Registry).

Inclusion/exclusion criteria:

All patients living and/or treated in Switzerland with an IBrainD specified in the following list diagnosed from 2005 onward and with a disease onset before the age of 18.

* Optic neuritis
* Transverse myelitis
* Acute disseminated encephalomyelitis
* Multiple sclerosis
* Neuromyelitis optica spectrum disorders
* Myelin oligodendrocyte glycoprotein antibody-associated disease
* Anti-NMDA-R associated autoimmune encephalitis
* Anti-GAD65 associated autoimmune encephalitis
* Anti-AMPAR-1/2 associated autoimmune encephalitis
* Anti-Lgi-1 associated autoimmune encephalitis
* Anti-CASPR-2 associated autoimmune encephalitis
* Anti-GABAR-1/2 associated autoimmune encephalitis
* Onconeuronal antibody (Hu, Ri, Yo, Amphiphysin, CRMP-5, Ma-1, Ma-2, SOX-1) associated autoimmune encephalitis
* Hashimoto encephalopathy
* CNS vasculitis
* CNS sarcoidosis
* CNS Lupus
* Rasmussen's encephalitis

Excluded are patients with:

1. Neurological symptoms due to infectious diseases of the CNS
2. Genetic/metabolic causes of central demyelinating diseases
3. Neurological symptoms due to Guillain-Barré-Syndrome

Registration of Patients and Collection of Medical Data:

Pediatricians, pediatric neurologists, neurologists, specialists in rehabilitation, and primary care physicians at the participating centers are responsible to identify children with the listed IBrainDs during regular medical consultations. Upon identification, treating physicians inform patients and their parents orally and in writing about the Swiss-Ped-IBrainD. Patients (and their legal representatives if applicable) who want to participate must give their informed consent. Once a patient consents to participate, their medical data will be entered in the registry.

The diagnostic workup and treatment of patients continue as usual and are independent from participation; no examination will be carried out specifically for the Swiss-Ped-IBrainD.

Medical data is collected through the following sources:

* Medical records and reports
* Oral/written information from treating physician
* Oral/written information from patient/family
* Routine statistics and other medical registries
* Questionnaires for patients and families The data collection focuses on diagnostic, follow-up, and relapse variables.

Routine data and linkages:

Communities; Federal Statistical Office (e.g. the birth register, cause of death statistics, hospital statistics)

Current status:

Since 2020, the investigators have included 128 people diagnosed with an IBrainD.

Funding:

* Schweizerische Multiple Sklerose Gesellschaft
* PedNet Bern
* SwissPedRegistry, University of Bern
* Roche Pharma (Switzerland) Ltd
* Novartis Pharma Schweiz AG
* Biogen
* Sanofi
* Anna Mueller Grocholski-Stiftung
* Gottfried und Julia Bangerter-Rhyner Stiftung
* Fondation Johanna Dürmüller-Bol

Eligibility criteria: Inclusion Criteria:

All patients living and/or treated in Switzerland with an IBrainD specified in the following list diagnosed from 2005 onward and with a disease onset before the age of 18.

* Written informed consent by patients (and/or legal representative(s), if applicable)
* Optic Neuritis
* Transverse Myelitis
* Acute disseminated encephalomyelitis
* Multiple Sclerosis
* Neuromyelitis Optica Spectrum Disorders
* Myelin oligodendrocyte glycoprotein antibody-associated disease
* Anti-NMDA-R Encephalitis
* Anti-GAD65 Associated Autoimmune Encephalitis
* Anti-AMPAR-1/2 Associated Autoimmune Encephalitis
* Anti-Lgi-1 Associated Autoimmune Encephalitis
* Anti-CASPR-2 Associated Autoimmune Encephalitis
* Anti-GABAR-1/2 Associated Autoimmune Encephalitis
* Onconeuronal Antibody (Hu, Ri, Yo, Amphiphysin, CRMP-5, Ma-1, Ma-2, SOX-1) Associated Autoimmune Encephalitis
* Hashimoto Encephalopathy
* CNS Vasculitis
* CNS Sarcoidosis
* CNS Lupus
* Rasmussen Encephalitis

Exclusion Criteria:

* Neurological symptoms due to infectious diseases of the CNS
* Genetic/metabolic causes of central demyelinating diseases
* Neurological symptoms due to Guillain-Barré-Syndrome

Primary outcomes:
measure: Personal data
timeFrame: At registration (Life-long; Up to 80 years)
measure: Diagnosis
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Age at diagnosis
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: First symptoms
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Age at first symptoms
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Diagnostic delay
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Hospitalization
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Rehabilitation
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Death date
timeFrame: Life-long; Up to 80 years
measure: Death cause
timeFrame: Life-long; Up to 80 years
measure: Change in EDSS
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Change in Neurostatus
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Change in medication
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Change in Education
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Change in MRI data
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Change in MRI data
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Change in laboratory test data
timeFrame: Until reaching of adulthood (0 to 18 years)
measure: Electrophysiological testing
timeFrame: Until reaching of adulthood (0 to 18 years)
Secondary outcomes:
measure: Future questionnaires
timeFrame: Life-long; Up to 80 years; Will mainly concern childhood (until reaching of adulthood; 0 to 18 years)
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
state: Aargau
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
state: Graubünden
city: St.Gallen
country: Switzerland
facility: Children's Hospital of Eastern Switzerland
state: Saint Gallen
city: Bellinzona
country: Switzerland
facility: Pediatric Institute of Southern Switzerland, Ospedale San Giovanni
state: Ticino
city: Lausanne
country: Switzerland
facility: University Children's Hospital Lausanne (CHUV)
state: Vaud
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
state: Zurich
city: Basel
country: Switzerland
facility: University Children's Hospital Basel, UKBB
city: Bern
country: Switzerland
facility: University Children's Hospital, Inselspital Bern
city: Bern
country: Switzerland
facility: Institute of Social and Preventive Medicine, University of Bern
city: Fribourg
country: Switzerland
facility: Hôpital Fribourgeois - Freiburger Spital
city: Geneva
country: Switzerland
facility: University Hospitals of Geneva (HUG)
city: Luzern
country: Switzerland
facility: Kinderspital Zentralschweiz
city: Zurich
country: Switzerland
facility: University Children's Hospital Zurich
Study officials:
affiliation: ISPM, University of Bern, Bern; Kinderspital Zentralschweiz, Luzern
name: Sandra Bigi, PD MD
role: PRINCIPAL_INVESTIGATOR
affiliation: ISPM, University of Bern, Bern Kinderspital Zentralschweiz, Luzern
name: Sandra Bigi, PD MD
role: STUDY_DIRECTOR
References: