West Nile VirusPROWENINCT04371003
Prospective Investigation of Oxidative Stress in West Nile Virus Infection
An observational study of West Nile Virus and West Nile Fever, run by Institute of Tropical Medicine, Belgium at 1 site in Romania.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- West Nile Virus, West Nile Fever, West Nile Fever Encephalitis
- How many people
- 0 participants
- Where
- 1 siteRomania
- Study dates
- 1 Sep 2020to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
- Keywords
- Genome sequencing, composite diagnosis
- Medical subject headings
- West Nile Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 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.
Measured: at recruitment, month 3 and month 12
MRI abnormalities
Part of descriptive analysis of clinical markers of disease severity
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Confirmed WNV infection is defined as one or more of following criteria:
- Seroconversion of anti-WNV IgG antibodies (Indirect immunofluorescence testing (IIFT) Flavivirus 2, Euroimmun®, Lübeck, Germany) in convalescent serum (20 days after symptom onset) (all participants)
- 4-fold increase of anti-WNV IgG antibodies in convalescent serum, compared to the screening sample (IIFT).
- Anti-WNV IgM antibody detection (ELISA) in CSF* (at VBH) (*CSF sampled only when clinically indicated).
- Positive WNV-specific RT-PCR result in serum, urine or CSF in samples obtained at screening.
- Virus isolation by outgrowth assay in samples obtained at screening
Measured: 20 days
Description of molecular epidemiology of infecting WNV strain(s) and viral outgrowth diagnostic performance.
The time frame for WNV detection after symptom onset by real-time reverse transcriptase polymerase chain reaction (RT-PCR) or virus isolation by outgrowth from blood or CSF is limited by the fast decline of circulating virus. Because the WNV RNA detection window in urine can be longer (up to 14 days), RT-PCR will be performed on all clinical samples at recruitment. The target sequences are a conserved region in the 5'UTR region and part of the capsid gene of WNV and detects both lineage 1 and 2 WNV. WNV has been successfully isolated from urine, in approx. 40% of samples obtained within 8 days of symptom onset. WNV isolation will be attempted in low-passage Vero E6 cells and BHK21 cells from urine samples with a high WNV RNA load (Cycle threshold (Ct)- values <30).
Measured: 20 days
Identification of potential genetic signatures that correlate with virulence (neuro-invasion and morbidity) in our cohort.
Whole genome sequencing (WGS) will be performed on a subset of RT-PCR positive serum, urine and CSF samples. This will allow us to investigate the temporal and spatial compartmentalization of the West Nile lineages in Romania as well as expand our understanding of genetic compartmentalization within hosts (urine, serum, CSF). In addition, the obtained isolates will be sequenced (from the viral outgrowth assay) to assess potential adaptations the virus undergoes during isolation. Finally, in a genome wide association study, the obtained viral sequences will be compared with the prospectively collected clinical data, to identify potential genetic signatures that correlate with virulence, neuroinvasion and morbidity. Our data will be compared to existing data on genetic determinants of virulence such as the presence of a glycosylation site in the E protein, substitutions in non-structural proteins 3, 4B or 5, or variation in the 3' noncoding region.
Measured: 20 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2020
- Study start1 Sep 2020 (estimated)
- Primary completion1 Oct 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Why it stopped: Study proposal was not accepted for funding and therefore not further explored at this stage.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for West Nile VirusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Tropical Medicine, Belgium
- Sponsor type
- University, hospital or other
- Collaborators
- Victor Babes Hospital, Bucharest, Romania, Universiteit Antwerpen
- Responsible party
- Sponsor
- Investigators
- Koen Vercauteren, Principal investigator, Institute of Tropical Medicine AntwerpNina Hermans, Principal investigator, Universiteit AntwerpenCorneliu Popescu, Principal investigator, Victor Babes Hospital, Bucharest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04371003
- Sponsor's protocol ID
- ITM202005
- Acronym
- PROWENI
- Status last verified
- Feb 2021
- First submitted
- 9 Apr 2020
- Last updated
- 10 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Investigation of Oxidative Stress in West Nile Virus Infection
- ClinicalTrials.gov ID
- NCT04371003
- Acronym / sponsor ID
- PROWENI / ITM202005
- Conditions
- West Nile Virus, West Nile Fever, West Nile Fever Encephalitis, West Nile Fever Meningitis, West Nile Meningitis, West Nile Virus Meningoencephalitis
- Keywords
- Genome sequencing, composite diagnosis
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Study proposal was not accepted for funding and therefore not further explored at this stage.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Institute of Tropical Medicine, BelgiumUniversity, hospital or other
- Collaborators
- Victor Babes Hospital, Bucharest, Romania, Universiteit Antwerpen
- Study start
- 1 Sep 2020 (estimated)
- Primary completion
- 1 Oct 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 1 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Measure the redox status
Time frame: at recruitment, 10 days post-symptom onset and 20 days post symtom onset.
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.
Assessment of Neurologic deficits
Time frame: At recruitment, month 3 and month 12
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
Neuropsychologic performance
Time frame: 20 days post-symtom onset, month 3 and month 12
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
Longitudinal assessment of functional status Study the neurologic and neuropsychologic sequelae of WNV infection during a 12-month followup period.
Time frame: at recruitment, month 3 and month 12
ECOG/WHO PS during a 12-month followup.
MRI abnormalities
Time frame: at recruitment, month 3 and month 12
Part of descriptive analysis of clinical markers of disease severity
Brain iron content
Time frame: at recruitment, month 3 and month 12
Part of the descriptive analysis of clinical markers of disease severity: Qualitative analysis per neuroanatomical region by iron-sensitive MRI sequence (SWI)
Ophthalmological abnormalities
Time frame: at recruitment, with a follow-up of clinically indicated.
As part of the descriptive analysis of clinical markers of disease severity ophthalmologic abnormalities will be assessed by slit lamp examination
serum S100b concentration
Time frame: at recruitment, 10 days post symptom onset and 20 days post symptom onset
As part of the descriptive analysis of clinical markers of disease severity S100b concentration will be measured to asses the Blood-Brain barrier integrity
serum NSE concentration
Time frame: at recruitment, 10 days post symptom onset and 20 days post symptom onset
As part of the descriptive analysis of clinical markers of disease severity NSE concentration will be measured to asses the Blood-Brain barrier integrity
3 secondary outcomes
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
Time frame: 20 days
Description of molecular epidemiology of infecting WNV strain(s) and viral outgrowth diagnostic performance.
Time frame: 20 days
Identification of potential genetic signatures that correlate with virulence (neuro-invasion and morbidity) in our cohort.
Time frame: 20 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Koen Vercauteren principal investigator
Institute of Tropical Medicine Antwerp
Nina Hermans principal investigator
Universiteit Antwerpen
Corneliu Popescu principal investigator
Victor Babes Hospital, Bucharest
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of West Nile Virus and West Nile Fever, run by Institute of Tropical Medicine, Belgium at 1 site in Romania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 10 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure the redox status (time frame: at recruitment, 10 days post-symptom onset and 20 days post symtom onset.). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2021.