Clinical trial NCT00138463: West Nile Virus Natural History
Official title: Investigation of the Natural History of West Nile Virus Infection in Patients With Recently Acquired West Nile Fever or Neuroinvasive Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: West Nile Virus
Keywords: West Nile Virus, Neuroinvasive Disease
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2005-08-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults, 18 and older, all study participants must have been diagnosed with West Nile Virus (WNV) disease within the four months prior to enrollment.

Brief summary: West Nile Virus causes an infection that is spread to humans when bitten by certain types of mosquitoes. Mosquitoes become infected by biting infected birds. The purpose of this study is to find out more about West Nile Virus, which may assist in the design of better treatments. The study will be looking at the effects of the disease on individuals, specifically their nervous systems, and the outcomes of the disease. Study participants will include 120 adults ages 18 and older, who have either a fever and/or changes in their neurological (involving the brain and nervous system) status due to documented West Nile Virus infection. Study procedures will include physical examinations, blood tests, urine tests, cerebral spinal fluid (fluid in and around the brain and spinal cord) tests, and neurological (nervous system) testing. Study participants will be followed for 12 months.

Detailed description: This is a multi-center, prospective, natural history study designed to characterize West Nile Virus (WNV) disease, including functional and neurologic outcomes, in study participants with laboratory documented WNV infection that have symptoms consistent with WNV neuroinvasive disease or WNV fever. The objectives of the study are to: identify and describe the mortality and morbidity, specifically neurologic and functional outcomes of patients with WNV; characterize the clinical course and diverse manifestations of WNV disease; and assess the kinetics of humoral immune responses to WNV infection, and to correlate these responses with clinical outcomes. The study will enroll a proposed sample size 120 study participants ages 18 and older. All study participants will undergo a series of laboratory, neurologic, and physical examinations and will be followed prospectively for one year to characterize the spectrum and sequelae of WNV disease. When patients meet inclusion criteria, informed consent will be obtained, and blood will be collected to perform polymerase chain reaction (PCR), immunoglobulin (Ig)M, and IgG testing for WNV infection. Urine PCR for WNV will also be obtained. Upon enrollment (Day 1), a medical and surgical history, review of systems, travel, vector and blood product history will be obtained, and the baseline neurologic and clinical status will be evaluated. A clinical assessment, including a physical examination, vital signs and laboratory assessment will be performed. Based on history a pre-illness neurologic functional score will be estimated, using the Barthel Index (BI) and the Modified Rankin Scale (MRS). Investigators will assess a Day 1 functional score, using the BI, the Modified Mini-Mental Status Examination (3MS), the Glasgow Outcome Score (GOS), and the Glasgow Coma Scale (GCS) if hospitalized and recorded answers to questions abstracted from the MRS on the day of entry into the study. At study visit Day 1 ± 3, cerebrospinal fluid (CSF) will be obtained and tested for cell count, differential, protein and glucose, IgM, IgG and PCR for WNV infection. If a study participant has a lumbar puncture conducted for standard of care at any time up to 72 hours prior and up to 72 hours after study enrollment, a repeat lumbar puncture will not be necessary if an adequate aliquot of CSF is available for shipment to the Collaborative Antiviral Study Group (CASG) Virology Laboratory and if the required cell count, differential, protein and glucose tests were performed. A brain Magnetic Resonance Imaging (MRI) scan will be done on study visit Day 1 ± 3. If the brain MRI scan on study visit Day 1 ± 3 suggests abnormalities, a repeat MRI scan will be conducted at study visit Day 30 ± 5. If changes (either improvement or worsening) in the WNV related lesions have occurred since the MRI conducted on study visit Day 1 ± 3, a third MRI will be conducted on study visit Day 90 ± 14. Subsequent MRIs will be conducted at study visits 180 ± 21 and 365 ± 30 only if the WNV related lesions continue to improve or worsen: any two MRIs where the WNV related lesions remain stable will obviate the need for further MRI scans. There will be study visits at Day 1, Day 14 ± 3, Day 30 ± 5, Day 90 ± 14, Day 180 ± 21, and Day 365 ± 30. At these visits a brief physical examination will be done, a functional score will be assigned, and blood will be obtained for serologic WNV studies. Neurological endpoints will include the GCS and 4 validated functional and cognitive scoring scales: The BI, MRS, GOS, and 3MS. MRI of spinal cord, electromyogram and nerve conduction studies will be included when available.

Eligibility criteria: Inclusion Criteria:

Patients, regardless of race or gender, who consent and meet entry criteria, will be enrolled.

* Greater than or equal to 18 years of age
* Documented West Nile Virus (WNV) infection (fever or neuroinvasive disease) that began within four months prior to study entry. Illness onset is defined as the first visit to a medical care provider where compatible symptoms (see cohort A and B below) are documented.
* Local laboratory documentation of WNV infection as defined by positive immunoglobulin (Ig) M and/or polymerase chain reaction (PCR) for WNV in serum or cerebrospinal fluid (CSF) concurrent with or following illness onset.
* Qualification for A or B Cohort.

Cohort A: Neuroinvasive Disease Cohort:

* Fever (temperature greater than 38 degrees Celsius) documented by a health care provider.
* AND: at least one of the following, as documented by a health care provider and in the absence of a more likely clinical explanation:

  1. Acutely altered mental status (e.g., disorientation, obtundation, stupor, or coma),
  2. Other acute signs of central or peripheral neurologic dysfunction (e.g., paresis or paralysis, nerve palsies, sensory deficits, abnormal reflexes, generalized convulsions, or abnormal movements), or
  3. CSF pleocytosis (white blood cell count greater than or equal to 4 per mm\^3 corrected for red blood cell contamination in CSF) associated with illness clinically compatible with meningitis (e.g., headache or stiff neck).

     Cohort B: West Nile Virus Fever Cohort:
* Temperature greater than 38 degrees Celsius as documented by a health care provider.

Exclusion Criteria:

* Unable to obtain valid informed consent.
* Alternate explanation (as determined by the investigator) for clinical findings (such as structural brain lesion, cerebrovascular accident, or other infectious disease).
* Evidence of a microbial organism demonstrable on gram or fungal stain of cerebrospinal fluid (CSF) within four months prior to study entry.
* Investigator's opinion that patient would be unable to adhere to protocol requirements.

Primary outcomes:
measure: Identify and describe the mortality and morbidity, specifically neurologic and functional outcomes of patients with West Nile Virus disease.
timeFrame: Duration of Study.
measure: Characterize the clinical course and diverse manifestations of West Nile Virus disease.
timeFrame: Duration of Study.
measure: Assess the kinetics of humoral immune responses to West Nile Virus infection, and correlate these responses with clinical outcomes.
timeFrame: Analysis.
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama Medical Center
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Harbor City
country: United States
facility: Kaiser Permanente South Bay Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Santa Rosa
country: United States
facility: Santa Rosa Kaiser Medical
state: California
city: Denver
country: United States
facility: Kaiser Permanente/Franklin Medical Center
state: Colorado
city: Idaho Falls
country: United States
facility: Idaho Falls Infectious Diseases, PLLC
state: Idaho
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: National Institutes of Health
state: Maryland
city: St. Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Butte
country: United States
facility: Mercury Street Medical Group
state: Montana
city: Broken Bow
country: United States
facility: Central Nebraska Medical Clinic
state: Nebraska
city: Omaha
country: United States
facility: VA Medical Center - Omaha
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Belleville
country: United States
facility: St. George University Clara Maas Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Pawtucket
country: United States
facility: Memorial Hospital of RI
state: Rhode Island
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
Study officials:
References:
citation: Hart J Jr, Tillman G, Kraut MA, Chiang HS, Strain JF, Li Y, Agrawal AG, Jester P, Gnann JW Jr, Whitley RJ; NIAID Collaborative Antiviral Study Group West Nile Virus 210 Protocol Team. West Nile virus neuroinvasive disease: neurological manifestations and prospective longitudinal outcomes. BMC Infect Dis. 2014 May 9;14:248. doi: 10.1186/1471-2334-14-248.