Searching for Persistence of Infection in Lyme Disease
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|ClinicalTrials.gov Identifier: NCT01143558|
Recruitment Status : Completed
First Posted : June 14, 2010
Last Update Posted : September 7, 2020
Lyme disease is an infection caused by Borrelia burgdorferi, a bacteria that is transmitted to humans by ticks. It can cause many different symptoms including rash, fever, headache, meningitis (infection of the central nervous system), and arthritis. While most patients improve after taking antibiotics, some patients continue to have symptoms. It is currently unknown why some patients continue to have symptoms. One possibility is that the antibiotics have not successfully gotten rid of all of the bacteria. Current tests for Lyme disease cannot tell whether the bacteria have been successfully eliminated from the body.
Xenodiagnosis is a way to look for Borrelia bacteria using the animal that usually hosts them, Ixodes scapularis (also known as the deer tick). This method takes advantage of the evolution of the bacteria and the insect that transmits the infection, which can make the insect particularly good at finding the agent. In studies of animals, xenodiagnosis may be more sensitive than current tests for detecting the presence of the Lyme disease bacteria. Researchers are interested in using xenodiagnosis to determine whether uninfected ticks that feed on humans who have been infected with Lyme disease bacteria can detect the continued presence of live bacteria.
- To determine whether xenodiagnosis can be used to successfully investigate the presence of Lyme disease bacteria.
- Individuals at least 18 years of age who are in one of the following categories:
- Have had the erythema migrans rash (a symptom of Lyme infection) and received antibiotic therapy less than 4 months ago (but have not had antibiotics in the previous month).
- Have the erythema migrans rash and received less than 2 days of antibiotic therapy.
- Have been diagnosed with early or late Lyme disease, have received antibiotic therapy, but still have high levels of antibodies against the bacteria at least 6 months after therapy, and have not received antibiotics in the past 3 months.
- Have been diagnosed with early or late Lyme disease, have received antibiotic therapy, and have new complaints of fatigue or other symptoms that are persistent for at least 6 months after completion of antibiotic therapy, and have not received antibiotics in the past 3 months.
- Have been diagnosed with Lyme arthritis and have not yet received antibiotic therapy.
- Healthy volunteers who have not had Lyme disease will also be included in this study.
- Participants will have an initial visit for a physical examination, medical history, and blood sample.
- For the first study visit, researchers will place a strip of filter paper or a small plastic container with 20 to 30 disease-free ticks on the participant s skin. If possible, the ticks will be placed at the site of a Lyme disease rash or another suspicious area, or on the nondominant forearm. Participants will be asked to keep the ticks in place, and will keep a diary card at home to record any symptoms or problems.
- The ticks will be collected 4 to 6 days after placement. At that visit, participants will have a skin biopsy taken of the area tested, a blood sample will be collected, and participants will receive a new diary card to keep until the next clinic visit.
- After 1 month, participants will provide a final blood sample, and will receive a follow-up phone call 2 months afterward.
|Condition or disease||Intervention/treatment||Phase|
|Lyme Disease||Device: Lyme Disease Xenodiagnosis||Early Phase 1|
Lyme disease is the most common vector borne disease in the United States. Although antibiotic therapy is clinically effective in treating the symptoms of Lyme disease for most patients early in the course of disease, a significant number of patients who receive therapy report persistent symptoms. The cause of persistent symptoms after antibiotic therapy for Lyme disease is an area of great controversy. Recent studies have shown that the organism (Borrelia burgdorferi) may persist in animals after antibiotic therapy and can be detected by using the natural tick vector (Ixodes scapularis) to acquire the organism through feeding (xenodiagnosis). Whether this occurs in humans is unknown. Currently available tests for human Lyme disease do not allow determination of persistent infection after antibiotic therapy.
In this proposal, the utility of xenodiagnosis for identifying persistence of B. burgdorferi in treated human Lyme disease will be tested in up to 120 subjects with various stages of Lyme disease with 30 healthy adults to serve as controls. Subjects will be followed for approximately 3 months. In Objective #1, subjects who have the characteristic erythema migrans (EM) rash and have been treated with antibiotics early (within 3 weeks of infection) in the course of Lyme disease will be tested. After completion of antibiotic therapy, 25-30 larval Ixodes ticks will be allowed to feed on the subject and biopsies of the EM site will be performed. Repleted ticks will be collected and tested for the presence of B. burgdorferi. In Objective #2, similar studies will be performed, but enrollment will target subjects with elevated C6 (region 6 of the VlsE surface protein of B. burgdorferi) antibody levels. In Objective #3, patients with persistent symptoms after antibiotic therapy will be evaluated. As an attempt to increase the chances of a positive xenodiagnosis in humans, patients with EM who are in the first 2 days of antibiotic therapy and patients with untreated Lyme arthritis will also be evaluated. Evidence that B. burgdorferi can be recovered by xenodiagnosis after antibiotic therapy in subjects with continued symptoms would change the current paradigm for potential mechanisms of disease and provide researchers and clinicians a tool for identifying patients with persistent infection. In Objective #4 we will assess the safety of the planned xenodiagnostic procedure in humans. All individuals who underwent xenodiagnosis under the study will be assessed for adverse events.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||45 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Searching for Persistence of Infection in Lyme Disease|
|Actual Study Start Date :||November 4, 2010|
|Actual Primary Completion Date :||December 30, 2014|
|Actual Study Completion Date :||December 30, 2014|
All cohorts undergo the same intervention with the study device.
Device: Lyme Disease Xenodiagnosis
Clean laboratory-bred ticks are the FDA registered IDE. These ticks are placed on patients to search for evidence of Borrelia burgdorferi.
- To assess the safety of the planned xenodiagnostic procedure in humans. All individuals who underwent xenodiagnosis under the study will be assessed for adverse events [ Time Frame: full duration of the study ]AE reporting per protocol toxicity table
- To perform xenodiagnosis on subjects who have the characteristic EM rash and have been treated with antibiotics early in the course of Lyme disease. [ Time Frame: Samples collected during tick removal visit. ]PCR and culture of samples
- To perform xenodiagnosis on subjects who have a high C6 ELISA titer after antibiotic therapy. [ Time Frame: Samples collected during tick removal visit. ]PCR and culture of samples
- To perform xenodiagnosis on subjects with post Lyme disease syndrome. [ Time Frame: Samples collected during tick removal visit. ]PCR and culture of samples
- To perform xenodiagnosis on subjects with newly diagnosed EM lesions that are within 48 hrs of starting antibiotics. [ Time Frame: Samples collected during tick removal visit. ]PCR and culture of samples
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): NCT01143558
|United States, Connecticut|
|New Haven, Connecticut, United States, 06510-8005|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|United States, Massachusetts|
|Boston, Massachusetts, United States, 01536|
|Principal Investigator:||Adriana R Marques, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|