A Prospective Study of Acute Flaccid Myelitis (AFM) to Define Natural History, Risk Factors and Pathogenetic Mechanisms

The overall objective of the NIAID-funded study is to create a biorepository of specimens and associated clinical and outcome data for use in future studies of AFM, including virologic or immunologic assessments.

The University of Alabama at Birmingham (UAB) is coordinating and implementing the study and is also opening the first clinical study site.

Brief Summary: AFM is a rare but serious neurologic disease characterized by sudden muscle weakness and paralysis. It appears to occur mostly in children, often following a mild respiratory illness. As of August 2, 2019, 574 confirmed cases of AFM had been reported in the United States since August of 2014.

Study Description: Patients with suspected AFM (onset of flaccid limb weakness within the previous 30 days) are eligible to enroll in the study. Investigators will assess participants at four-time points within the first month of enrollment and will ask participants to return for additional follow up visits at 3 months, 7 months and 1 year. Neurologic improvements will be tracked over time, and samples will be collected and stored in a biorepository for use in future research studies. Household contacts, such as siblings, will be eligible to participate in the study as a control or comparison group.

Additional clinical research sites in the U.S., Canada, the United Kingdom, and Peru are expected to open in the coming months.

Contacts: David W Kimberlin MD, 205-934-5316, dkimberlin@peds.uab.edu

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

A list of potential study locations to be opened are shown below. For all sites please contact Dr. Kimberlin’s office (dkimberlin@peds.uab.edu or sdavis@peds.uab.edu) and the Central Unit personnel will be able to provide more current information for these study locations.

United States, Alabama – Children’s of Alabama – UAB Hospital (open as of 8.23.19)

            Birmingham, AL

United States, Alabama – University of South Alabama

            Mobile, AL

United States, Arkansas – Arkansas Children’s Hospital – Infectious Diseases

            Little Rock, AR

United States, California – University of Southern California

            Los Angeles, CA

United States, California – Children’s Hospital of Orange County

            Orange, CA

United States, California – University of California, San Diego, Rady Children’s Hospital

            San Diego, CA

United States, California – Kaiser Permanente San Francisco Medical Center and UCSF Pediatrics, Benioff Children’s Hospital

            San Francisco, CA

United States, California – Stanford University

            Stanford, CA

United States, Colorado – University of Colorado Health Science Center, Children’s Hospital Colorado

            Denver, CO

United States, District of Columbia – Children’s National Medical Center

            Washington, DC

United States, Florida – University of South Florida Morsani College of Medicine

            Tampa, FL

United States, Georgia – Emory Children’s Center

            Atlanta, GA

United States, Kentucky – University of Louisville School of Medicine – Norton Children’s Hospital

            Louisville, KY

United States, Louisiana – Louisiana State University Health Sciences Center

            Shreveport, LA

United States, Maryland – Johns Hopkins University School of Medicine

            Baltimore, MD

United States, Massachusetts – Boston Children’s Hospital

            Boston, MA

United States, Minnesota – University of Minnesota

            Minneapolis, MN

United States, Mississippi – University of Mississippi – Children’s Infectious Diseases

            Jackson, MS

United States, Missouri – Washington University School of Medicine in St. Louis – Center for Clinical Studies

            St. Louis, MO

United States, Nebraska – Children’s Hospital, University of Nebraska Medical Center

            Omaha, NE

United States, New Jersey – The Children’s Hospital at St. Peters University Hospital

            New Brunswick, NJ

United States, New York – Cohen Children’s Medical Center

            Queens, NY

United States, New York – University of Rochester Medical Center

            Rochester, NY

United States, New York – The State University of New York Upstate Medical University

            Syracuse, NY

United States, North Carolina – Carolinas Medical Center (Atrium Health) – Pediatrics – Infectious Diseases

            Charlotte, NC

United States, Ohio – Nationwide Children’s Hospital –

            Columbus, OH

United States, Pennsylvania – Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine

            Philadelphia, PA

United States, Pennsylvania – Children’s Hospital of Pittsburgh of UPMC – Pediatric Infectious Diseases

            Pittsburgh, PA

United States, South Carolina – Medical University of South Carolina

            Charleston, SC

United States, Tennessee – Vanderbilt University Medical Center

            Nashville, TN

United States, Texas – University of Texas Southwestern Medical Center

            Dallas, TX

United States, Texas – Cook Children’s Medical Center

            Fort Worth, TX

United States, Washington – Children’s Hospital and Regional Medical Center

            Seattle, WA

United States, Wisconsin – Children’s Hospital of Wisconsin-Milwaukee

            Milwaukee, WI

Canada, Ontario – The Hospital for Sick Children (Sickkids), University of Toronto

            Toronto, Ontario, Canada

United Kingdom – Sites to Be Determined

Peru – Sites to Be Determined


A Phase II, Single-Stage, Single-Arm Investigation of Oral Valganciclovir Therapy in Infants with Asymptomatic Congenital Cytomegalovirus Infection

The purpose of this study is to evaluate if using Valganciclovir as a treatment to prevent sensorineural hearing loss in babies born with an infection called congenital Cytomegalovirus (CMV) is helpful. Congenital means that it occurred before birth. We are looking for babies who were born with no outward symptoms (asymptomatic) of this infection and were not tested at birth. Valganciclovir is the approved drug that doctors currently use for the treatment of congenital CMV infection. This drug is used in babies born with outward symptoms (symptomatic) and who have had a confirmed positive CMV test done after delivery. Valganciclovir has been shown in earlier studies to be effective in preventing hearing loss or hearing deterioration in babies with symptomatic CMV disease. 


An Observational Study of Acyclovir Pharmacokinetics, Viral Population Kinetics, and Potential Biomarkers of Disease Severity in Neonatal Herpes Simplex Virus Infections

This is an observational study, not a treatment study. The purpose of this study is to learn more about how to best diagnose babies with HSV (Herpes Simplex Virus) infections, and also how babies respond to the standard treatment for this infection. We will screen babies who are suspected of having an HSV infection and have come to the emergency room or the hospital for this kind of evaluation and testing. We will be enrolling babies that are < 42 days old.


Natural History of Infection Caused by BK Virus (and other Opportunistic Viral Pathogens) in Renal and Renal-Pancreas Transplant Recipients  

The BK viremia natural history study enrolled first subject on 5 Feb 2015. Three sites are actively recruiting for subjects. There are 234 subjects enrolled. There are about 33 subjects identified with BK viremia based on plasma BK viral load by PCR. The investigators participating in this study are continuing recruitment for potential subjects. The projected total enrollment number is 450 subjects. The current funding cycle ends 9/2017 with an extension to 9/2018 expected.


Identification of Herpes Simplex Virus (HSV) Shedding In The Female Genital Tract of Pregnant and Nonpregnant Women by GeneXpert PCR, Standard PCR, and Culture  [Pediatric study—15 sites]  

The Genexpert study began with the first subject enrolled on 29 April 2014. Investigational research teams have almost completely enrolled the study. There are less than 450 subjects needed to complete the protocol target enrollment of 12,500. Eight investigators are actively recruiting for subjects. The current funding cycle ends 9/2017 although an extension to 9/2018 is expected. 


A Phase II Randomized and Controlled Investigation of Six Weeks of Oral Valganciclovir Therapy in Infants and Children with Congenital Cytomegalovirus Infection and Hearing Loss  [Pediatric study—17 sites] 

This is a study for children who have been diagnosed with hearing loss in one or both ears in the past 12 weeks and may have an infection called congenital Cytomegalovirus (CMV). Congenital means that it occurred before birth. The purpose of this study is to compare the effect on hearing and neurological outcomes of infants between 1 month and 4 years of age who receive 6 weeks of Valganciclovir with children who do not receive this drug. We also want to learn about the safety of giving Valganciclovir to these babies and children. At this time, there is no standard of care for doctors to use to treat children for hearing loss because of a virus. 


Evaluation of the Pharmacokinetics and Pharmacodynamics of Ganciclovir in Premature Infants Receiving Treatment for Cytomegalovirus Infection [Pediatric study—15 sites]  

This is not a treatment study. It is a study to learn about what is the safest and correct dose of a medicine called IV Ganciclovir that is used to treat congenital Cytomegalovirus (CMV) Infection in premature babies. Congenital means that it occurred before birth. This medicine is given through an IV and is ordered by your primary doctor. This medicine has been studied in adults, in children and in babies who are not premature. We want to know how to treat premature babies safely. We are enrolling premature babies who have already been diagnosed with CMV infection, and whose doctor has already decided to treat them with IV Ganciclovir. We will study levels of the medicine in the blood while the baby is on treatment to determine the safest and best dose for premature babies.