Next Generation Sequencing Detection of Lyme Disease

• ClinicalTrials.gov Identifier: NCT03505879
• Recruitment Status: Recruiting
• First Posted: April 23, 2018
• Last Update Posted: September 7, 2018
• Sponsor: Stony Brook University
• Collaborator: Karius, Inc.
• Information provided by (Responsible Party): Christy Beneri, Stony Brook University

Study Description

Brief Summary:

Next Generation Sequencing is able to sequence all DNA detected in a sample, including short strands. This differs from PCR testing, which uses pre-determined DNA primers to detect a limited number of specific, often large, strands of DNA. The investigators will test the ability of NGS to detect Borrelia burgdorferi DNA in the blood of study participants with an erythema migrans rash. This study will compare 20 study participants with the EM rash (cases) to 10 healthy study participants without an EM rash (controls). The investigators will collect clinically relevant information and send both currently used Lyme testing and Next Generation Sequencing in both the cases and controls. The case participants will then have two requested (but not required) follow up appointments at 1-3 weeks and 2-3 months later to obtain updated clinical information and send repeat NGS testing. The investigators will then conduct basic descriptive statistics on the results to determine if NGS is capable of detecting Lyme DNA during the acute phase of infection.

Condition or disease
Lyme Disease; Pediatric Infectious Disorder; Erythema Migrans

Study Design

• Study Type: Observational
• Estimated Enrollment: 30 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Next Generation Sequencing to Detect Borrelia Burgdorferi DNA in the Blood of Pediatric Patients With Lyme-Related Erythema Migrans
• Actual Study Start Date: July 24, 2018
• Estimated Primary Completion Date: December 31, 2019
• Estimated Study Completion Date: March 1, 2020

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Ability of Next Generation Sequencing to detect Borrelia burgdorferi DNA in blood [ Time Frame: 5 months ]
   To determine if Next Generation Sequencing (NGS) is able to detect Borrelia burgdorferi DNA in the blood of pediatric patients with clinically-diagnosed erythema migrans (EM).
2. NGS detection of Borrelia burgdorferi DNA in blood compared to serology [ Time Frame: 5 months ]
   To compare the ability to detect Borrelia burgdorferi infection among pediatric patients with an erythema migrans using NGS versus serology

Secondary Outcome Measures :

1. Changes in NGS detection of Borrelia burgdorferi DNA in blood over time [ Time Frame: 5 months ]
   To determine if the detection of Borrelia burgdorferi DNA in pediatric patients with an EM changes over time after appropriate antibiotic treatment of Lyme disease.

Biospecimen Retention:   Samples With DNA

Whole blood samples for detection of infectious pathogens by next generation sequencing

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Cases will include pediatric patients age 1 to <18 years old who currently have a rash consisting of single of multiple erythema migrans and have not previously had Lyme disease.

Controls will include pediatric patients age 1 to <18 years old who are currently healthy with no signs or symptoms of Lyme disease and have not previously had Lyme disease.

Criteria

Lyme disease subjects (Cases):

Inclusion criteria:

1. Age 1 to <18 years old
2. The subject has a rash consistent with either a single or multiple erythema migrans
3. The subject has spent time in a Lyme-endemic area during the previous month

Exclusion criteria:

1. Past infection with Lyme disease
2. Received oral or IV antibiotics within 1 month prior to presentation

Healthy subjects (Controls):

Inclusion criteria:

1. Age 1 to <18 years old
2. Seen at Stony Brook General Pediatric clinic for a Well Child Exam
3. The subject has spent time in a Lyme-endemic area during the previous month

Exclusion Criteria

1. Past infection with Lyme disease
2. Current symptoms of Lyme disease (erythema migrans, persistent headaches, neck stiffness, Bell's palsy, palpitations, shortness of breath, joint swelling)
3. Current symptoms concerning for infection other than Lyme disease

Contacts and Locations

Contacts

Contact: Christy Beneri, DO; (631) 444-7692; Christy.Beneri@stonybrookmedicine.edu

Contact: Andrew Handel, MD; (631) 444-7692; Andrew.handel@stonybrookmedicine.edu

Locations

United States, New York

Clinical Research Center; Recruiting

Setauket, New York, United States, 11733-9219

Contact: Wendy Mattias 631-444-6900 wendy.mattias@stonybrookmedicine.edu

Contact: Erin Infanzon 631-444-8832 erin.infanzon@stonybrookmedicine.edu

Principal Investigator: Christy A Beneri

Sub-Investigator: Andrew Handel

Sponsors and Collaborators

Stony Brook University

Karius, Inc.

More Information

Publications:

Schwartz AM, Hinckley AF, Mead PS, Hook SA, Kugeler KJ. Surveillance for Lyme Disease - United States, 2008-2015. MMWR Surveill Summ. 2017 Nov 10;66(22):1-12. doi: 10.15585/mmwr.ss6622a1.

Theel ES. The Past, Present, and (Possible) Future of Serologic Testing for Lyme Disease. J Clin Microbiol. 2016 May;54(5):1191-6. doi: 10.1128/JCM.03394-15. Epub 2016 Feb 10. Review.

Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of lyme borreliosis. Clin Microbiol Rev. 2005 Jul;18(3):484-509. Review.

Babady NE, Sloan LM, Vetter EA, Patel R, Binnicker MJ. Percent positive rate of Lyme real-time polymerase chain reaction in blood, cerebrospinal fluid, synovial fluid, and tissue. Diagn Microbiol Infect Dis. 2008 Dec;62(4):464-6. doi: 10.1016/j.diagmicrobio.2008.08.016. Epub 2008 Oct 22.

Kalish RA, McHugh G, Granquist J, Shea B, Ruthazer R, Steere AC. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after active Lyme disease. Clin Infect Dis. 2001 Sep 15;33(6):780-5. Epub 2001 Aug 10.

da Fonseca AJ, Galvão RS, Miranda AE, Ferreira LC, Chen Z. Comparison of three human papillomavirus DNA detection methods: Next generation sequencing, multiplex-PCR and nested-PCR followed by Sanger based sequencing. J Med Virol. 2016 May;88(5):888-94. doi: 10.1002/jmv.24413. Epub 2015 Nov 6.

Abril MK, Barnett AS, Wegermann K, Fountain E, Strand A, Heyman BM, Blough BA, Swaminathan AC, Sharma-Kuinkel B, Ruffin F, Alexander BD, McCall CM, Costa SF, Arcasoy MO, Hong DK, Blauwkamp TA, Kertesz M, Fowler VG Jr, Kraft BD. Diagnosis of Capnocytophaga canimorsus Sepsis by Whole-Genome Next-Generation Sequencing. Open Forum Infect Dis. 2016 Jul 12;3(3):ofw144. eCollection 2016 Sep.

• Responsible Party: Christy Beneri, Assistant Professor of Pediatrics, Stony Brook University
• ClinicalTrials.gov Identifier: NCT03505879 History of Changes
• Other Study ID Numbers: 1205731-1
• First Posted: April 23, 2018
• Last Update Posted: September 7, 2018
• Last Verified: September 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Christy Beneri, Stony Brook University:

Next Generation Sequencing

Additional relevant MeSH terms:

Communicable Diseases; Infection; Lyme Disease; Erythema Chronicum Migrans; Glossitis, Benign Migratory; Erythema; Skin Diseases; Skin Manifestations; Signs and Symptoms; Borrelia Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Tick-Borne Diseases; Spirochaetales Infections; Skin Diseases, Bacterial; Skin Diseases, Infectious; Glossitis; Tongue Diseases; Mouth Diseases; Stomatognathic Diseases