Lyme Test Indication Combinations (LyTIC) Study

NCT ID: NCT03201042

Last Updated: 2018-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Total Enrollment

410 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-06-08

Study Completion Date

2018-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

To establish performance of individual tests and combinations of tests (serological, molecular and cellular tests) in early Lyme infection diagnosis

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The present study aims to investigate the performance characteristics of both established and new assays for Borrelia burgdorferi infection and to assess the relative performance of appropriate combinations of these tests. The study will also investigate the effect of the time course of the infection and its treatment on the outcomes for the various tests. Polymerase Chain Reaction(PCR), serology and T cell based tests will be performed. In addition, tests for Babesia, Anaplasma, Ehrlichia and Rickettsia will also be performed as these pathogens can be carried by the same tick that carries Borrelia and may result in coinfection.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Lyme Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1a:Lyme patients- Erythema Migrans(EM)rash present

Patients with newly diagnosed Lyme disease based on the presence of a physician-documented EM rash. PCR, serology and Tcell based assay.

PCR based assay

Intervention Type DIAGNOSTIC_TEST

Whole blood specimens will be tested for the presence of Borrelia DNA by PCR in a two-step test (Imugen). In Cohort 1a and 1b. The first step tests for the presence of any Borrelia DNA. The second step is employed on positive samples and tests for the presence of either B. burgdorferi DNA or B. miyamotoi DNA. Positivity by PCR has a short but early window in the infection cycle for Borrelia burgdorferi and results may enable this window period and diagnosis rates to be better defined.

In addition co-infection PCR analysis will be performed for the presence of Babesia, Anaplasma or Ehrlichia DNA (Imugen).

Serology based assay

Intervention Type DIAGNOSTIC_TEST

1. The Imugen Lyme Antibody Analysis which includes immunoglobulin M (IgM),immunoglobulin G (IgG), and immunoglobulin A (IgA) antibody capture immunoassay and IgG and IgM based Western blots. In Cohort 1a and 1b.
2. The Immunetics C6 Lyme ELISA assay.
3. A 2-tier Lyme test performed and interpreted according to Centers for Disease Control (CDC) Guidelines
4. A Rickettsia antibody test will be used to identify Spotted Fever and Typhus fever groups infections.

Lyme test methodologies generally indicate a need to run a combination of tests in order to overcome limitations in either sensitivity or specificity of the various individual tests. Performance of all these tests on the same set of samples should enable both individual and combinatorial performance values to be calculated and compared.

Tcell based assay

Intervention Type DIAGNOSTIC_TEST

A research based ELISpot assay will be performed on peripheral blood mononuclear cells (PBMC) extracted from whole blood samples to test for presence of T cells activated against Borrelia antigens. Unlike serology based methods, this signal may not persist over extended periods of time in the absence of Borrelia antigens. The diagnostic window may be different for a test measuring adaptive immune response (i.e. T cells) and thus such test may identify patients with undetectable antibody response and may aid sensitivity of diagnosis.

1b:Lyme patients no typical EM

Patients documented symptoms of early Lyme disease, without a typical EM rash present, and the physician's intention to treat for Lyme disease. PCR, serology and Tcell based assay

PCR based assay

Intervention Type DIAGNOSTIC_TEST

Whole blood specimens will be tested for the presence of Borrelia DNA by PCR in a two-step test (Imugen). In Cohort 1a and 1b. The first step tests for the presence of any Borrelia DNA. The second step is employed on positive samples and tests for the presence of either B. burgdorferi DNA or B. miyamotoi DNA. Positivity by PCR has a short but early window in the infection cycle for Borrelia burgdorferi and results may enable this window period and diagnosis rates to be better defined.

In addition co-infection PCR analysis will be performed for the presence of Babesia, Anaplasma or Ehrlichia DNA (Imugen).

Serology based assay

Intervention Type DIAGNOSTIC_TEST

1. The Imugen Lyme Antibody Analysis which includes immunoglobulin M (IgM),immunoglobulin G (IgG), and immunoglobulin A (IgA) antibody capture immunoassay and IgG and IgM based Western blots. In Cohort 1a and 1b.
2. The Immunetics C6 Lyme ELISA assay.
3. A 2-tier Lyme test performed and interpreted according to Centers for Disease Control (CDC) Guidelines
4. A Rickettsia antibody test will be used to identify Spotted Fever and Typhus fever groups infections.

Lyme test methodologies generally indicate a need to run a combination of tests in order to overcome limitations in either sensitivity or specificity of the various individual tests. Performance of all these tests on the same set of samples should enable both individual and combinatorial performance values to be calculated and compared.

Tcell based assay

Intervention Type DIAGNOSTIC_TEST

A research based ELISpot assay will be performed on peripheral blood mononuclear cells (PBMC) extracted from whole blood samples to test for presence of T cells activated against Borrelia antigens. Unlike serology based methods, this signal may not persist over extended periods of time in the absence of Borrelia antigens. The diagnostic window may be different for a test measuring adaptive immune response (i.e. T cells) and thus such test may identify patients with undetectable antibody response and may aid sensitivity of diagnosis.

Cohort 2: healthy controls

Patients drawn from Lyme disease non-endemic areas and subjects with known exposure to Lyme disease will be excluded. PCR, serology and Tcell based assay.

PCR based assay

Intervention Type DIAGNOSTIC_TEST

Whole blood specimens will be tested for the presence of Borrelia DNA by PCR in a two-step test (Imugen). In Cohort 1a and 1b. The first step tests for the presence of any Borrelia DNA. The second step is employed on positive samples and tests for the presence of either B. burgdorferi DNA or B. miyamotoi DNA. Positivity by PCR has a short but early window in the infection cycle for Borrelia burgdorferi and results may enable this window period and diagnosis rates to be better defined.

In addition co-infection PCR analysis will be performed for the presence of Babesia, Anaplasma or Ehrlichia DNA (Imugen).

Serology based assay

Intervention Type DIAGNOSTIC_TEST

1. The Imugen Lyme Antibody Analysis which includes immunoglobulin M (IgM),immunoglobulin G (IgG), and immunoglobulin A (IgA) antibody capture immunoassay and IgG and IgM based Western blots. In Cohort 1a and 1b.
2. The Immunetics C6 Lyme ELISA assay.
3. A 2-tier Lyme test performed and interpreted according to Centers for Disease Control (CDC) Guidelines
4. A Rickettsia antibody test will be used to identify Spotted Fever and Typhus fever groups infections.

Lyme test methodologies generally indicate a need to run a combination of tests in order to overcome limitations in either sensitivity or specificity of the various individual tests. Performance of all these tests on the same set of samples should enable both individual and combinatorial performance values to be calculated and compared.

Tcell based assay

Intervention Type DIAGNOSTIC_TEST

A research based ELISpot assay will be performed on peripheral blood mononuclear cells (PBMC) extracted from whole blood samples to test for presence of T cells activated against Borrelia antigens. Unlike serology based methods, this signal may not persist over extended periods of time in the absence of Borrelia antigens. The diagnostic window may be different for a test measuring adaptive immune response (i.e. T cells) and thus such test may identify patients with undetectable antibody response and may aid sensitivity of diagnosis.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

PCR based assay

Whole blood specimens will be tested for the presence of Borrelia DNA by PCR in a two-step test (Imugen). In Cohort 1a and 1b. The first step tests for the presence of any Borrelia DNA. The second step is employed on positive samples and tests for the presence of either B. burgdorferi DNA or B. miyamotoi DNA. Positivity by PCR has a short but early window in the infection cycle for Borrelia burgdorferi and results may enable this window period and diagnosis rates to be better defined.

In addition co-infection PCR analysis will be performed for the presence of Babesia, Anaplasma or Ehrlichia DNA (Imugen).

Intervention Type DIAGNOSTIC_TEST

Serology based assay

1. The Imugen Lyme Antibody Analysis which includes immunoglobulin M (IgM),immunoglobulin G (IgG), and immunoglobulin A (IgA) antibody capture immunoassay and IgG and IgM based Western blots. In Cohort 1a and 1b.
2. The Immunetics C6 Lyme ELISA assay.
3. A 2-tier Lyme test performed and interpreted according to Centers for Disease Control (CDC) Guidelines
4. A Rickettsia antibody test will be used to identify Spotted Fever and Typhus fever groups infections.

Lyme test methodologies generally indicate a need to run a combination of tests in order to overcome limitations in either sensitivity or specificity of the various individual tests. Performance of all these tests on the same set of samples should enable both individual and combinatorial performance values to be calculated and compared.

Intervention Type DIAGNOSTIC_TEST

Tcell based assay

A research based ELISpot assay will be performed on peripheral blood mononuclear cells (PBMC) extracted from whole blood samples to test for presence of T cells activated against Borrelia antigens. Unlike serology based methods, this signal may not persist over extended periods of time in the absence of Borrelia antigens. The diagnostic window may be different for a test measuring adaptive immune response (i.e. T cells) and thus such test may identify patients with undetectable antibody response and may aid sensitivity of diagnosis.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Cohort 1a (typical EM and intention to treat):

Inclusion

1. Documented new onset Lyme disease EM rash (single or multiple) with photographic evidence provided to Oxford Immunotec.
2. Patient must be able to provide blood sample at the initial visit (prior to treatment initiation) and subsequent samples according to the schedule.
3. Patients 5 years of age or older, with a minimum weight of 40 pounds.
4. Patient able to read English and to give consent to study participation.
5. If patient is younger than 18 years of age a legally authorized representative must provide consent.

Cohort 1b (no typical EM; Lyme disease symptoms; intention to treat):

Inclusion

1. Patients with suspected Lyme disease, based on physician's examination, where the physician has the intention to treat for Lyme disease (i.e. patients who following initial examination were prescribed treatment for Lyme disease).
2. Documented new onset of Lyme disease symptoms without a typical EM rash or with no rash. If a rash is present, photographic evidence must be provided.
3. Patient must be able to provide blood sample at the initial visit (prior to treatment initiation) and subsequent samples according to the schedule.
4. Patients 5 years of age or older, with a minimum weight of 40 pounds.
5. Patient able to read English and to give consent to study participation.
6. If patient is younger than 18 years of age a legally authorized representative must provide consent.

Cohort 2 (Healthy subjects):

Inclusion

1. Subjects 5 years of age or older, with a minimum weight of 40 pounds.
2. Subjects never diagnosed with any tick borne disease including Lyme disease
3. Subjects able to read English and to give consent to study participation.
4. If subject is younger than 18 years of age a legally authorized representative must provide consent.

Exclusion Criteria

* Exclusion Cohort 1a (typical EM and intention to treat):

1. Patients with Lyme-like symptoms lasting longer than 1 month prior to study enrolment.
2. Patients receiving treatment for any tick borne disease (including Lyme disease) prior to enrolment.
3. Patients who received a Lyme vaccination.
4. Patients with anemia defined as a serum hemoglobin \<10gm/dL.
5. Patients who are participating in, or plan to participate in, any investigational drug study.
6. Patients who are considered unsuitable for the study by the Investigator.

Cohort 1b (no typical EM; Lyme disease symptoms; intention to treat):

1. Patients with Lyme-like symptoms lasting longer than 1 month prior to study enrolment.
2. Patients receiving treatment for any tick borne disease (including Lyme disease) prior to enrolment.
3. Patients who received a Lyme vaccination.
4. Patients with anemia defined as a serum hemoglobin \<10gm/dL.
5. Patients who are participating in, or plan to participate in, any investigational drug study.
6. Patients who are considered unsuitable for the study by the Investigator.

Cohort 2 (Healthy subjects):

Exclusion

1. Subjects with a history of tick bite
2. Subjects with past or current tick borne disease diagnosis
3. Subjects at risk for tick borne diseases including Lyme disease
4. Subjects residing in endemic regions for tick borne diseases: Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia and Wisconsin.
5. Subjects who have ever visited non-urban areas of endemic regions for tick borne diseases: Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia and Wisconsin.
Minimum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Oxford Immunotec

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Paradigm Clinical Research

Redding, California, United States

Site Status

Coastal Connecticut Research

New London, Connecticut, United States

Site Status

Circle CARE Center

Norwalk, Connecticut, United States

Site Status

Orthopaedic Foundation for Active Lifestyles, Inc

Stamford, Connecticut, United States

Site Status

Delaware Integrated Medicine

Georgetown, Delaware, United States

Site Status

Eastern Research, Inc.

Hialeah, Florida, United States

Site Status

South Florida Clinical Trials SFCT, A member of the Alliance, Inc.

Hialeah, Florida, United States

Site Status

South Coast Research Center

Miami, Florida, United States

Site Status

Advance Clinical Research

Meridian, Idaho, United States

Site Status

Acadia Clinical Research

Bangor, Maine, United States

Site Status

Integrative Health Center of Maine

Portland, Maine, United States

Site Status

Centennial Medical Group

Eldridge, Maryland, United States

Site Status

Klein & Associates, MD, PA

Hagerstown, Maryland, United States

Site Status

MD Medical Research, Inc.

Oxon Hill, Maryland, United States

Site Status

Rockville Internal Medicine Group

Rockville, Maryland, United States

Site Status

NECCR Primacare Research,LLC

Fall River, Massachusetts, United States

Site Status

Cape Cod Hospital

Hyannis, Massachusetts, United States

Site Status

Metromedic Walk In

New Bedford, Massachusetts, United States

Site Status

The Research Institute

Springfield, Massachusetts, United States

Site Status

NECCR Primacare Research, LLC

Westford, Massachusetts, United States

Site Status

Clinical Pharmacology Study Group

Worcester, Massachusetts, United States

Site Status

Asthma and Allergy Institute of MI

Clinton Township, Michigan, United States

Site Status

Oakland Medical Research

Troy, Michigan, United States

Site Status

Pinnacle Research

Sartell, Minnesota, United States

Site Status

Andrea Gaito

Basking Ridge, New Jersey, United States

Site Status

MAffiliated Medical Associates

Florham Park, New Jersey, United States

Site Status

Modern Medical

Brooklyn, New York, United States

Site Status

Private Practice-Johnathan Liebowitz

Brooklyn, New York, United States

Site Status

NY Arthritis Clinic

Brooklyn, New York, United States

Site Status

Regional Clinical Research, Inc.

Endwell, New York, United States

Site Status

Private Practice-David Wurwitz

Flushing, New York, United States

Site Status

Adirondack Medical Research Center

Glens Falls, New York, United States

Site Status

NYCT, A member of Alliance, Inc.

New York, New York, United States

Site Status

Mid Hudson Medical Research

Newburgh, New York, United States

Site Status

John T. Mather Hospital

Port Jefferson, New York, United States

Site Status

Rapid Medical Research

Cleveland, Ohio, United States

Site Status

Buckeye Health and Research

Columbus, Ohio, United States

Site Status

Toledo Institute of Clinical Research

Toledo, Ohio, United States

Site Status

Bally Medical Group

Barto, Pennsylvania, United States

Site Status

Boyertown Medical Assoc.

Boyertown, Pennsylvania, United States

Site Status

Collegeville Family Practice

Collegeville, Pennsylvania, United States

Site Status

Brandywine Clinic

Downingtown, Pennsylvania, United States

Site Status

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Site Status

Pediatric Medical Associates of NTN/ABG

East Norriton, Pennsylvania, United States

Site Status

Liberty Family Practice/Square 1

Erie, Pennsylvania, United States

Site Status

Detweiler Family Practice

Lansdale, Pennsylvania, United States

Site Status

Green and Seidner Family Practice

Lansdale, Pennsylvania, United States

Site Status

Suburban Research Assoc.

Media, Pennsylvania, United States

Site Status

Brookside Family Practice and Pediatrics

Pottstown, Pennsylvania, United States

Site Status

Spring-Ford Family Practice

Royersford, Pennsylvania, United States

Site Status

Safe Harbor Clinical Research

East Providence, Rhode Island, United States

Site Status

Ocean State Clinical Research

Lincoln, Rhode Island, United States

Site Status

NECCR Primacare Research, LLC

Portsmouth, Rhode Island, United States

Site Status

Atascosa Clinical Trial

Lytle, Texas, United States

Site Status

Brookside Family Health Care

Hinesburg, Vermont, United States

Site Status

Millennium Clincial Trials

Arlington, Virginia, United States

Site Status

Burke Internal Medicine

Burke, Virginia, United States

Site Status

The Education and Research Foundation, Inc.

Lynchburg, Virginia, United States

Site Status

Manassas Clinical Research Center

Manassas, Virginia, United States

Site Status

Exemplar Research

Morgantown, West Virginia, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

L3

Identifier Type: -

Identifier Source: org_study_id