Prospective Investigation of Oxidative Stress in West Nile Virus Infection

NCT04371003 | Withdrawn

• 1 other identifier: ITM202005
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The investigator hypothesizes that oxidative stress responses to West Nile virus infection in the central nervous system determine the severity of infection and the long-term neurological, neuropsychological and functional sequelae of West Nile Neuroinvasive Disease.

Conditions

West Nile Virus; West Nile Fever; West Nile Fever Encephalitis; West Nile Fever Meningitis; West Nile Meningitis; West Nile Virus Meningoencephalitis; West Nile Fever Meningoencephalitis; West Nile Fever With Neurologic Manifestation; Oxidative Stress

Keywords

Genome sequencing; composite diagnosis

Outcome Measures

Primary Outcomes (9)

• Measure the redox status

  A multiparameter indexes of oxidative stress will be calculated to measure and summarize the redox status in cases and age matched controls. Association between the redox status and clinical, neuropsychological and radiological outcomes will be investigated. We will also examine the relative sensitivity of separate biomarkers of oxidative stress and autophagy as clinical predictors of WNV infection severity.

  at recruitment, 10 days post-symptom onset and 20 days post symtom onset.

• Assessment of Neurologic deficits

  As part of the descriptive analysis of biomarkers of disease severity and to study to neurologic sequelae of WNV infection. Will be assessed: specifically assessments of cranial nerves II- XII, motor strength in upper and lower extremities, sensory testing for pinprick and vibration, deep tendon reflexes, gait, coordination, and movement abnormalities

  At recruitment, month 3 and month 12

• Neuropsychologic performance

  Study the neuropsychologic sequelae of WNV infection during a 12-month followup period in following key domains: Attention, Memory, Executive Function, Emotion \& Social Cognition, Psychomotor Speed

  20 days post-symtom onset, month 3 and month 12

• Longitudinal assessment of functional status Study the neurologic and neuropsychologic sequelae of WNV infection during a 12-month followup period.

  ECOG/WHO PS during a 12-month followup.

  at recruitment, month 3 and month 12

• MRI abnormalities

  Part of descriptive analysis of clinical markers of disease severity

  at recruitment, month 3 and month 12

• Brain iron content

  Part of the descriptive analysis of clinical markers of disease severity: Qualitative analysis per neuroanatomical region by iron-sensitive MRI sequence (SWI)

  at recruitment, month 3 and month 12

• Ophthalmological abnormalities

  As part of the descriptive analysis of clinical markers of disease severity ophthalmologic abnormalities will be assessed by slit lamp examination

  at recruitment, with a follow-up of clinically indicated.

• serum S100b concentration

  As part of the descriptive analysis of clinical markers of disease severity S100b concentration will be measured to asses the Blood-Brain barrier integrity

  at recruitment, 10 days post symptom onset and 20 days post symptom onset

• serum NSE concentration

  As part of the descriptive analysis of clinical markers of disease severity NSE concentration will be measured to asses the Blood-Brain barrier integrity

  at recruitment, 10 days post symptom onset and 20 days post symptom onset

Secondary Outcomes (3)

• Analysis of laboratory performance characteristics (e.g. sensitivity) of WNV-specific RT-PCR and viral isolation in clinical samples, compared to composite diagnosis of WNV infection

  20 days

• Description of molecular epidemiology of infecting WNV strain(s) and viral outgrowth diagnostic performance.

  20 days

• Identification of potential genetic signatures that correlate with virulence (neuro-invasion and morbidity) in our cohort.

  20 days

Study Arms (3)

WNND

40 subject with West-Nile Neuroinvasive Disease will be recruited

WNF

40 subject with West-Nile Fever will be recruited

controls

20 control will be recruited. These controls will be aged matched to the cases.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will be recruited from VBH emergency and outpatient departments in Bucharest, Romania, from the onset of the WNV transmission season in 2020 until November 2023. The incidence of WNV and WNND in South-Eastern Romania was 0.5 per 100,000 inhabitants in 2016, and has been increasing steadily 35. Romania reported 277 WNND cases with 43 deaths in 2018, and 66 WNND cases with 8 deaths in 2019 3. VBH is a tertiary care facility that serves a population of 3 million people (15% of Romania's population). Its catchment area covers more than 80% of the territories in Romania that reported WNV transmission and has in recent years been the largest single medical center to care for WNV infected patients.

You may qualify if:

• Willing and able to provide written informed consent. If the clinical condition of the patient does not permit giving consent, informed consent will be obtained from the next of kin.
• Age 18 years or older
• for active cases: positive anti-WNV IGM antibodies in serum (or IgG in CSF if applicable)
• for active cases: presentation within (maximum) 7days of symptom onset
• for healthy controls: anti-WNV antibody naive (IgM and IgG in serum). The group of healthy controls will be selected to have an age similar distribution to the cases.

You may not qualify if:

• Evidence of active systemic infection in 3 months prior to recruitment
• Evidence of systemic inflammatory illness
• Clinical signs of neurodegenerative or neurologic disease other than WNND
• Pregnancy
• Active malignancy
• History of drug abuse

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• Victor Babes Hospital, Bucharest, Romania: collaborator
• Universiteit Antwerpen: collaborator

Study Sites (1)

Victor Babes Hospital

Bucharest, Romania

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

West Nile Fever

Condition Hierarchy (Ancestors)

Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Mosquito-Borne Diseases; Virus Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Study Officials

• Koen Vercauteren

  Institute of Tropical Medicine Antwerp

  PRINCIPAL INVESTIGATOR

• Nina Hermans

  Universiteit Antwerpen

  PRINCIPAL INVESTIGATOR

• Corneliu Popescu

  Victor Babes Hospital, Bucharest

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: May 1, 2020
• Study Start: September 1, 2020
• Primary Completion: October 1, 2023
• Study Completion: December 31, 2023
• Last Updated: February 10, 2021

Record last verified: 2021-02

Locations

RO (1)