The NOrwegian Tick-borne Encephalitis Study (NOTES)

The NOrwegian Tick-borne Encephalitis Study - NOTES: An Observational Study on Clinical Features, Long-term Outcomes and Immune Characteristics

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tick-Borne Encephalitis, European
• Intervention / Treatment: Other: No intervention

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.

• Study Type: Observational
• Enrollment (Actual): 153

Contacts and Locations

Study Locations

• Norway
  • Arendal, Norway
    • Sykehuset Sørlandet HF
  • Tønsberg, Norway
    • Sykehuset i Vestfold
  • Telemark
    • Skien, Telemark, Norway, 3710
      • Sykehuset Telemark HF

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe the acute phase clinical and immunological characteristics of TBE in Norway	clinical features and objective findings of the acute phase of the TBE-patients diagnosed with TBE in South-East Norway during 2018-2021	4 years
To investigate the impact of TBEV infection on health-related QOL in a one year follow-up study of a Norwegian patient cohort	A prospective multicenter study of health-related QOL one year after hospitalization with TBE in South-East Norway from 2019-2022. The self-reported health-related QOL (assessed by SF-36) of the TBE-patients, will be compared with the SF-36 reference values in the Norwegian population.	4 years
To investigate the impact of TBEV infection on long-term cognitive function in a one year follow-up study of a Norwegian patient cohort	A prospective multicenter study of self-reported cognitive function by BRIEF, FSS, HADS and EMQ, one year after hospitalization with TBE in South-East Norway from 2019-2022. The cognitive function, measured by PROMS, will be compared with PROMS from an included reference group from the patient's social environment.	5 years
To identify biomarkers in the cerebrospinal fluid (CSF) and blood, which serve as predictors for TBE severity and long-term complaints	FS-36 and BRIEF	5 years

Collaborators and Investigators

• Sponsor: Sykehuset Telemark
• Collaborators: Norwegian Institute of Public Health; Oslo University Hospital; Sorlandet Hospital HF; Sykehuset i Vestfold HF
• Investigators: Study Director: Hege Kersten, PhD, Study Director

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: November 26, 2021
• First Posted (Actual): November 30, 2021

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Tick-Borne Diseases; Neuroinflammatory Diseases; Encephalitis; Encephalitis, Tick-Borne
• Other Study ID Numbers: 96505

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No