Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Neurologic Manifestations of the Arbovirus Infection in Colombia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03206541
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : February 1, 2019
Sponsor:
Collaborators:
Universidad del Valle, Colombia
ZikaPLAN
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
This is a multi-center case-control study that aims to define the association between the exposure to an arbovirus infection and the development of a neurological syndrome in patients from Colombia. The study makes part of the Neurovirus Emerging in the Americas Study (NEAS) that is a collaborative effort that looks to combine the efforts of researchers, healthcare providers and patients in Colombia to establish a comprehensive registry of the clinical, radiological and laboratory profile of patients with new onset of neurological diseases associated mosquito-borne viruses, known as arboviruses.

Condition or disease
Encephalitis Myelitis Guillain-Barre Syndrome Cranial Nerve Palsies Meningitis Zika Virus Infection Dengue (Virus); Fever, Sandfly Chikungunya Fever

  Hide Detailed Description

Detailed Description:

NEAS is led by Dr. Carlos Pardo-Villamizar at Johns Hopkins University (JHU) and Drs. Beatriz Parra and Lyda Osorio at Universidad del Valle (UV) in Colombia. They have established a collaborative network with physicians, neurologists and experts in microbiology and epidemiology in that country. NEAS is actively recruiting patients in seven university-based hospitals in five Colombian cities. The protocol of the study has been approved in each of the participating centers.

NEAS prospective case-control study aims to define the association between the exposure to arbovirus (Zika, Dengue and Chikungunya) and the development of a neurological syndrome in patients from Colombia, a country with endemic transmission of arbovirus. The cases are defined as individuals that present with new onset of a neurological syndrome of unknown etiology, including but not limited to encephalitis, myelitis, meningitis, polyneuropathy/Guillain-Barre syndrome and cranial nerve involvement. There are two age-matched control groups: 1) household controls and 2) controls with a febrile syndrome of unknown etiology that do not present neurological involvement. The estimated sample size in the study is 50 participants in each group (cases and controls 1 and 2). The time to collect the complete sample size is between 12-24 months, and depends on the local incidence of cases.

Each center has a coordinator team that includes a neurologist, a physician - neurology or internal medicine resident -, and a research coordinator. The team is constantly screening the patients admitted to the center. The patients that fulfill the criteria for cases or controls are approached by the research coordinator who is in charge to inform the participant about the study and complete the informed consent. Then, the medical team perform the neurological evaluation, including the history and the physical exam according to the NEAS forms. Samples of blood and urine are collected in all participants. If a lumbar puncture is done as part of the standard of care, spinal fluid is also collected. Based on resources availability, the participants are followed every week for a 4-week period and in each visit a clinical assessment and sample collection are completed.

Demographic and clinical information, laboratory and imaging results are stored in a secured web-based database in the platform REDcap,based at JHU. Each center has a unique combination of a username and a password to enter the database and include the information of each participant in real time. Each center has access to the included information by the same center and no by other centers. Standardized forms (NEAS forms) were created by the study team that include relevant information necessary to achieved the aims of this study and guarantee the data consistency. Laboratory testing and imaging results are obtained from the medical records. A permanent monitoring of the data base is done by the teams at JHU and UV.

After the samples are collected they are shipped to the study core laboratory located at UV (Dr. Beatriz Parra). Each center has been trained in the correct handling, processing, and shipping of the samples. Once the samples are in the core laboratory, they are aliquoted and stored. Blood, urine and spinal fluid are tested by Real Time/Reverse Transcriptase (RT)- Polymerase Chain Reaction (PCR) for the presence of viral RNA (Ribonucleic Acid) of Zika virus and Dengue virus. Serum and spinal fluid are tested by ELISA for the detection of anti-flavivirus IgM and IgG. The results are shared with the local study team and with the medical team taking care of the participant. In addition, aliquots of samples are sent to JHU for additional immunological and virological assessments (Dr. Carlos Pardo-Vllamizar).

Standard Operative Procedures (SOP) have been created for patient recruitment and consent, REDcap data entering, and biosamples process and shipment. The statistical analysis will be done by epidemiologists at UV (Dr. Lyda Osorio) and it will include frequency measures and central tendency measures of the variables. The measure of the strength of association will be done using Odds ratio and confidence intervals.

DATA DICTIONARY

The variables are divided in three categories: demographic, clinical and laboratory. The most relevant variables collected in the study are described below.

Demographic variables:

  • Case: Case definition
  • Type of control: Control definition
  • Fulfillment of the inclusion criteria: Fulfillment of the inclusion criteria established by the protocol
  • Gender: Sexual phenotype of the participant supported by the medical records or ID
  • Age: Participant`s age according to the medical records or ID
  • Race: Phenotype reported by the participant
  • City of residence: Place where has mainly been in the last 3 months
  • City of report: Place where the participant is recruited to the study

Clinical variables:

  • General symptoms: Clinical manifestations consistent with decrease in the normal health shape of the participant
  • Onset of general symptoms: Date of the onset of general symptoms
  • Neurological symptoms: Clinical manifestations reflecting an abnormal functioning of the nervous system
  • Temporal profile: Time (in days) between the onset of general symptoms and neurological symptoms
  • Visit to endemic regions: History of have visited during the last 4 weeks regions with current local transmission of Zika, Dengue and/or Chikungunya virus
  • Past medical history: History of a disease diagnosed by the doctor or reported in the medical records during the past year
  • Family history: Diseases suffered by first or second consanguinity degree relatives diagnosed by the doctor or reported in the medical records
  • Recent vaccination: History of vaccination during the past 4 weeks before the onset of the neurological symptoms
  • Recent infectious disease: History of an infectious disease during the past 4 weeks before the onset of the neurological symptoms
  • Recent surgical procedure: History of a major surgical procedure during the past 4 weeks before the onset of the neurological symptoms
  • Date of physical exam: Date when physical exam was completed by the study team
  • Mental status: Range of own/outer consciousness
  • Orientation: Awareness of time, place and person
  • Dysarthria: Word articulation dysfunction secondary to a motor pathways damage
  • Attention deficit: Inability to selectively concentrate in an specific portion of the information
  • Cranial nerves abnormalities: Compromise of one/more of the cranial nerves detected on the physical exam
  • Muscle strength: Amount of strength done by a muscle against resistance
  • Deep tendon reflexes: Extension secondary to a deep tendon stimulus
  • Sensory deficit: Absence or abnormality in the sensory function
  • Romberg sign: Clinical sign suggesting sensory ataxia, secondary to dorsal columns abnormalities
  • Ataxia: Abnormal muscle coordination during voluntary movements
  • Muscle tone: Muscle resistance against passive movement
  • Urinary retention: Inability to complete bladder emptiness
  • Low rectal muscle tone: Decrease in the strength of the rectal sphincter
  • Abnormal movements: No voluntary movements, without purpose, secondary to a neurological dysfunction
  • Respiratory failure: Inability to perform an efficient gas exchange or to maintain normal levels of oxygen and/or carbon dioxide
  • Autonomic dysfunction: Abnormalities in the autonomic nervous system
  • Electromyography: Electrophysiological study of the muscle activity
  • Electroencephalogram: Electrophysiological study of the brain conduction
  • Brain MRI: Imaging study of the brain
  • Spinal cord MRI: Imaging study of the spinal cord
  • Rankin score: Functional scale for patients with neurological disorders
  • ASIA scale: Severity of spinal cord lesion

Laboratory variables:

  • Blood analysis: Include white blood cells count, platelets, hemoglobin, hematocrit and liver function enzymes.
  • Spinal fluid analysis: Includes leukocytes, glucose, proteins, red blood cells, oligoclonal bands, cultures, herpes virus PCR.
  • Virological analysis: Includes detection or absence of detection of IgM and IgG by ELISA, and the RNA by RT-PCR for Zika virus, Dengue virus and Chikungunya virus.

Layout table for study information
Study Type : Observational [Patient Registry]
Estimated Enrollment : 150 participants
Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 4 Weeks
Official Title: Neurovirus Emerging in the Americas Study (NEAS): Neurologic Manifestations of the Arbovirus Dengue, Chikungunya and Zika Infections in Colombia
Actual Study Start Date : January 1, 2016
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019


Group/Cohort
Cases
The cases are defined as individuals that present with new onset of a neurological syndrome of unknown etiology, including but not limited to encephalitis, myelitis, meningitis, polyneuropathy/Guillain-Barre syndrome and cranial nerve involvement.
Controls

There are two age-matched control groups:

  1. Household controls that have lived with the case for at least three months before the onset of neurological symptoms.
  2. Controls with a febrile syndrome of unknown etiology that do not present neurological involvement and is recruited in the same center as the case.



Primary Outcome Measures :
  1. Neurological outcomes in arbovirus infections [ Time Frame: 12-24 months ]
    Number of patients with neurological syndromes that have evidence of acute infection by Zika, Dengue or Chikungunya viruses assessed by IgM serology or polymerase chain reaction


Secondary Outcome Measures :
  1. Viral genotype [ Time Frame: 24-36 months ]
    Number of strains of Zika, Dengue and Chikungunya viruses assessed by genome sequencing

  2. Immune response [ Time Frame: 24-36 months ]
    Cellular immune response assessed by T-lymphocyte profiling in patients with confirmed arbovirus infection with and without neurological syndromes


Biospecimen Retention:   Samples With DNA
The study will retain blood (serum and plasma), urine, spinal fluid and saliva for cases and controls according to the protocol. The samples will remain in the core laboratory at UV and some of them will be shared with the JHU team.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   8 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The study population includes males and females over 8 years of age at risk of being infected by Dengue, Chikungunya or Zika viruses.
Criteria

Inclusion Criteria:

  • Male or female
  • Case or control definition
  • Informed consent or assent

Exclusion Criteria:

  • Known etiology for the acute neurological disorders
  • History of known neurological syndrome

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03206541


Contacts
Layout table for location contacts
Contact: Carlos A Pardo-Villamizar, MD 410-614-4548 cpardov1@jhmi.edu
Contact: Paula Barreras, MD 4432519229 pbarrer2@jhmi.edu

Locations
Layout table for location information
Colombia
Clinica Leon XIII Recruiting
Medellín, Antioquia, Colombia
Contact: Jorge A Jimenez-Arango, MD       jorge.neurologia@gmail.com   
Neuroclinica Recruiting
Medellín, Antioquia, Colombia
Contact: Jorge A Jimenez-Arango       jorge.neurologia@gmail.com   
Clinica La Misericordia Internacional Recruiting
Barranquilla, Atlantico, Colombia
Contact: Jose Vargas, MD       drjosevargasm@gmail.com   
Clinica Medilaser Recruiting
Neiva, Huila, Colombia
Contact: Jorge Angarita, MD       jorgeangarita@hotmail.com   
Hospital Universitario de Neiva Recruiting
Neiva, Huila, Colombia
Contact: Guillermo Gonzalez-Manrique, MD       feevon@hotmail.es   
Hospital Universitario de Narino Not yet recruiting
Pasto, Narino, Colombia
Contact: Julie Benavides, MSc       julie.benavidesm@campusucc.edu.co   
Hospital Universitario Erasmo Meoz Recruiting
Cúcuta, Norte De Santander, Colombia
Contact: Jairo Lizarazo, MD       jflizar@gmail.com   
Hospital Universitario del Valle Recruiting
Cali, Valle Del Cauca, Colombia
Contact: Gonzalo Zuniga, MD       gonzuga28@hotmail.com   
Sub-Investigator: Andres F Zea, MD         
Sponsors and Collaborators
Johns Hopkins University
Universidad del Valle, Colombia
ZikaPLAN
Investigators
Layout table for investigator information
Principal Investigator: Carlos A Pardo-Villamizar, MD Johns Hopkins University
Principal Investigator: Beatriz Parra, PhD Universidad del Valle
Principal Investigator: Lyda Osorio, PhD Universidad del Valle

Additional Information:

Study Data/Documents: Suplemental Data  This link exits the ClinicalTrials.gov site
This data set contains detailed information on a cohort of 68 cases with Guillain-Barre syndrome that was analyzed as part of NEAS. The NEAS forms used to collect clinical information are available at the end of the document.

Publications of Results:
Other Publications:
Layout table for additonal information
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03206541     History of Changes
Other Study ID Numbers: IRB00093149
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: February 1, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NEAS is part of the ZikaPLAN, which is a consortium led by the European Community. There is a plan of sharing information with other collaborators within the consortium. The information will include demographic information, laboratory results and neurological physical exam. No identifiers will be shared. The information will be obtained through the ongoing recruitment of patients. We plan to share the first set of information during the second semester of 2017.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Johns Hopkins University:
Neurological syndromes
Arbovirus infection
Additional relevant MeSH terms:
Layout table for MeSH terms
Guillain-Barre Syndrome
Infection
Communicable Diseases
Dengue
Chikungunya Fever
Zika Virus Infection
Arbovirus Infections
Meningitis
Encephalitis
Neurologic Manifestations
Myelitis
Cranial Nerve Diseases
Fever
Virus Diseases
Body Temperature Changes
Signs and Symptoms
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral
Central Nervous System Diseases
Nervous System Diseases
Brain Diseases
Alphavirus Infections
Togaviridae Infections
Polyradiculoneuropathy
Autoimmune Diseases of the Nervous System
Demyelinating Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases