Clinical trial NCT05138055: The NOrwegian Tick-borne Encephalitis Study
Official title: The NOrwegian Tick-borne Encephalitis Study - NOTES: An Observational Study on Clinical Features, Long-term Outcomes and Immune Characteristics
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Tick-Borne Encephalitis, European
Lead sponsor: Sykehuset Telemark
Sponsor class: OTHER_GOV
Collaborators: name: Sykehuset i Vestfold HF
name: Norwegian Institute of Public Health
name: Sorlandet Hospital HF
name: Oslo University Hospital
First posted: 2021-11-30
Enrollment: 153
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study population in substudy 1. Patients \> 16 years old diagnosed with acute infection caused by TBEV. The hospitals involved are Telemark and Vestfold. Study population in substudy 2. Patients \> 16 years old diagnosed with acute infection caused by TBEV. The hospitals involved are Telemark, Vestfold and Sørlandet.

Brief summary: During 2018, 2019, and 2020, the reported TBE-cases have increased markedly in Norway. Surveillance studies conducted by the Norwegian Institute of Public Health demonstrate that cases are associated with tick bites in the coastal areas of the Agder, Buskerud, and Vestfold and Telemark counties There is a urgent need for more knowledge of the consequences of TBE in Norway, in particular the identification of patients at risk of long-term sequela. Hence, the overall objective of this project is to gain more knowledge about the natural course of TBE in Norway, and its impact on long-term health-related quality of life and associated factors. Clinical data, biological sampling and PROMs are collected from TBE-infected patients admitted to three hospitals within the epidemic region in Norway.

Detailed description: This project is designed as a multicenter study divided into four sub-studies:

Substudy 1: A retrospective descriptive study of the clinical features and objective findings of the acute phase of the TBE-patients diagnosed with TBE in South-East Norway during 2018, 2019 and 2020.

Substudy 2: A prospective multicenter study of health related QOL one year after hospitalization with TBE in South-East Norway from 2019 - 2023. The self-reported health-related QOL (assesedby SF-36) of the TBE-patients will be compared with the SF-36 reference values in the Norwegian population.

Substudy 3: A prospective multicenter study of self-reported cognitive function one year after hospitalization with TBE in South-East Norway from 2019- 2023. The cognitive function, measured by PROMS, will be compared with PROMS from an included reference group from the patient's social environment.

Substudy 4: Analyses of biological samples collected at baseline, 3 months and 12 months after hospitalization for TBE in patients included in substudy 2 and 3. These analyses will be conducted to gain more knowledge of the pathogenesis of TBE infection and in particular, which molecular pathways and biomarkers that characterize the TBE infected patients who are hospitalized in Norway. Analyses to identify associations between the acute inflammatory response and long-term outcome will be performed.

Eligibility criteria: Inclusion Criteria:

1. Patient: The patients diagnosed with acute infection with TBEV at admission.
2. Control: same age (plus/minus 4 years), level of education (plus minus 2 years) and the same gender as patient.

Exclusion Criteria:

1. Patient: Patients who turn out to have different diagnose than acute infections with TBEV.
2. Control: Previously infection with tick-borne encephalitis virus.
3. The patients who were diagnosed with typical symptoms and only TBEV IgM-test must take a blood sample for IgG analyses. If the TBE IgG analysis is negative, the patient will be excluded.

Primary outcomes:
measure: To describe the acute phase clinical and immunological characteristics of TBE in Norway
timeFrame: 4 years
measure: To investigate the impact of TBEV infection on health-related QOL in a one year follow-up study of a Norwegian patient cohort
timeFrame: 4 years
measure: To investigate the impact of TBEV infection on long-term cognitive function in a one year follow-up study of a Norwegian patient cohort
timeFrame: 5 years
measure: To identify biomarkers in the cerebrospinal fluid (CSF) and blood, which serve as predictors for TBE severity and long-term complaints
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Skien
country: Norway
facility: Sykehuset Telemark HF
state: Telemark
city: Arendal
country: Norway
facility: Sykehuset Sørlandet HF
city: Tønsberg
country: Norway
facility: Sykehuset i Vestfold
Study officials:
affiliation: Study director
name: Hege Kersten, PhD
role: STUDY_DIRECTOR
References:
citation: Veje M, Nolskog P, Petzold M, Bergstrom T, Linden T, Peker Y, Studahl M. Tick-Borne Encephalitis sequelae at long-term follow-up: a self-reported case-control study. Acta Neurol Scand. 2016 Dec;134(6):434-441. doi: 10.1111/ane.12561. Epub 2016 Jan 26.