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Trial record 2 of 9 for:    Open Studies | lyme disease | United States | Ireland | Adult

Xenodiagnosis After Antibiotic Treatment for Lyme Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT02446626
First received: May 13, 2015
Last updated: August 31, 2016
Last verified: April 2016
  Purpose

Background:

The most common tick-borne illness in the United States, Lyme disease is caused by Borrelia burgdorferi bacteria that are transmitted to people by Ixodes scapularis ticks. Most cases of Lyme disease are cured by antibiotics, but some patients continue to experience symptoms despite the absence of detectable Lyme bacteria. Xenodiagnosis uses a vector to detect the presence of a disease-causing microbe.. Researchers will use live, laboratory-bred ticks to see if Lyme disease bacteria can be detected in people after completing antibiotic therapy and if that is more common in people who continue to experience symptoms such as fatigue and joint pain.

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Objectives:

- To see if ticks can be used to detect B. burgdorferi in people who have had Lyme disease and received antibiotic therapy and if it correlates with persistent symptoms.

Eligibility:

  • Adults at least 18 years old who have:
  • Untreated erythema migrans (the Lyme disease rash); OR
  • Untreated Lyme arthritis; OR
  • Continuing symptoms after treatment for Lyme disease; OR
  • Had Lyme disease and antibiotic treatment within the past 12 months.
  • Healthy volunteers

Design:

  • Participants will be screened with medical history, physical exam, and blood tests.
  • Visit 1:
  • Blood and urine tests, health questionnaire.
  • Up to 30 laboratory-bred, pathogen-free, larval ticks (each smaller than a poppy seed) will be placed under a dressing.
  • Participants may have two small biopsies of skin .
  • 4 6 days later, Visit 2:
  • Dressing will be removed and ticks will be collected.
  • Participants will answer symptom questions.
  • If many ticks are still attached, participants will have to come back the next day. If not enough ticks feed successfully, the procedure may be repeated.
  • Participants will keep a diary of symptoms for 30 days. Over 3 months, they will be return to the clinic 3 times to see how they feel and answer questionnaires. Test results will be discussed.

Condition Intervention Phase
Lyme Disease
Procedure: Skin biopsy
Procedure: Blood draw
Other: Xenodiagnosis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Xenodiagnosis After Antibiotic Treatment for Lyme Disease - Phase II Study

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • This study is powered to detect difference in the positivity rate between symptomatic and asymptomatic individuals. [ Time Frame: 4-6 weeks post tick removal visit, and approximately 3 months post tick removal visit. ] [ Designated as safety issue: No ]
  • The study will continue to assess the safety of xenodiagnosis in humans. [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 240
Study Start Date: May 2015
Estimated Study Completion Date: December 2030
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Patients with Lyme disease, post treatment
Procedure: Skin biopsy
Optional 2-3mm skin punch biopsies will be performed.
Procedure: Blood draw
Peripheral blood draws will be performed.
Other: Xenodiagnosis
Larval ticks will be obtained from Dr. Sam Telford from a laboratory maintained tick colony at Tufts Veterinary School. These ticks are hatchedfrom eggs laid by ticks that have fed only on specific pathogen free laboratory animals that were purchased from established vendors. Between 25-30 larval ticks that have been aged and are known to be ready to attach will be placed on the study participant.
Active Comparator: 2
Patients with post-Lyme disease complaints at least 12 months from initial treatment
Procedure: Skin biopsy
Optional 2-3mm skin punch biopsies will be performed.
Procedure: Blood draw
Peripheral blood draws will be performed.
Other: Xenodiagnosis
Larval ticks will be obtained from Dr. Sam Telford from a laboratory maintained tick colony at Tufts Veterinary School. These ticks are hatchedfrom eggs laid by ticks that have fed only on specific pathogen free laboratory animals that were purchased from established vendors. Between 25-30 larval ticks that have been aged and are known to be ready to attach will be placed on the study participant.
Active Comparator: 3
Acute erythema migrans patients (possible positive control)
Procedure: Skin biopsy
Optional 2-3mm skin punch biopsies will be performed.
Procedure: Blood draw
Peripheral blood draws will be performed.
Other: Xenodiagnosis
Larval ticks will be obtained from Dr. Sam Telford from a laboratory maintained tick colony at Tufts Veterinary School. These ticks are hatchedfrom eggs laid by ticks that have fed only on specific pathogen free laboratory animals that were purchased from established vendors. Between 25-30 larval ticks that have been aged and are known to be ready to attach will be placed on the study participant.
Active Comparator: 4
Lyme Arthritis patients (possible positive control)
Procedure: Skin biopsy
Optional 2-3mm skin punch biopsies will be performed.
Procedure: Blood draw
Peripheral blood draws will be performed.
Other: Xenodiagnosis
Larval ticks will be obtained from Dr. Sam Telford from a laboratory maintained tick colony at Tufts Veterinary School. These ticks are hatchedfrom eggs laid by ticks that have fed only on specific pathogen free laboratory animals that were purchased from established vendors. Between 25-30 larval ticks that have been aged and are known to be ready to attach will be placed on the study participant.
Active Comparator: 5
Healthy Volunteers (negative control)
Procedure: Skin biopsy
Optional 2-3mm skin punch biopsies will be performed.
Procedure: Blood draw
Peripheral blood draws will be performed.
Other: Xenodiagnosis
Larval ticks will be obtained from Dr. Sam Telford from a laboratory maintained tick colony at Tufts Veterinary School. These ticks are hatchedfrom eggs laid by ticks that have fed only on specific pathogen free laboratory animals that were purchased from established vendors. Between 25-30 larval ticks that have been aged and are known to be ready to attach will be placed on the study participant.

Detailed Description:

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.

We performed the first study of the use of I. scapularis larva for the xenodiagnosis of B. burgdorferi infection in humans. Our pilot study showed that xenodiagnosis was well tolerated with no severe adverse events (AEs). The most common AE was mild itching at the site. In this small pilot study, xenodiagnosis for B. burgdorferi was positive in 2 participants and indeterminate in 2 participants. Further studies are needed to determine the sensitivity of xenodiagnosis in evaluating the infection status of Lyme disease patients.

In this proposal, we want to further investigate the utility of xenodiagnosis for identifying persistence of infection with B. burgdorferi in treated human Lyme disease. Our objectives include assessing the link between detection of B. burgdorferi by xenodiagnosis and persistence of symptoms in patients diagnosed with Lyme disease, within 1 year, post therapy; compare the rate of detection of B. burgdorferi by xenodiagnosis after therapy in participants with posttreatment Lyme disease symptoms; identify subject characteristics related to the likelihood of detecting B. burgdorferi by xenodiagnosis including: time from infection, time between infection and therapy, time from therapy; and continue to assess the safety of xenodiagnosis in humans.

The results of study have the potential to resolve this long-standing controversy in Lyme disease pathogenesis. While xenodiagnosis is unlikely to be widely used in clinical practice due to the labor intensity and speed of testing, if our study shows a linkage between positive xenodiagnostic testing and persistence of symptoms after B. burgdorferi infection, it may prove to be a useful tool for testing new strategies for treatment and for correlation with more generally applicable diagnostic markers. Understanding the pathogenesis of persistent symptoms following Lyme disease, and identifying reliable diagnostic tests for determining the success of antibiotic therapy, is critical to the medical management of these patients.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA

Criteria for the diagnosis and therapy for Lyme disease can be found at The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America .

PATIENTS WITH LYME DISEASE, POST-THERAPY (N=100)

  1. Age 18 or older
  2. Lyme disease diagnosed in the previous 12 months, fulfilling the case definition of confirmed or probable Lyme disease by the CDC
  3. Completion of 1 course of antibiotics at least 3 months and up to 12 months between the end of the therapy and the xenodiagnostic procedure.
  4. Antibiotic treatment fulfills the Infectious Diseases Society of America guidelines for the recommended therapy for Lyme disease

PATIENTS WITH POST-LYME DISEASE COMPLAINTS AT LEAST 12 MONTHS FROM INITIAL TREATMENT (N=40)

  1. Age 18 or older
  2. Diagnosed with confirmed or probable Lyme disease fulfilling the case definition of Lyme disease by the CDC
  3. Received recommended antibiotic therapy for Lyme disease 5 at least 12 months between the end of the initial antibiotic therapy and the xenodiagnostic procedure.
  4. Persistent or recurrent symptoms that began or worsened within 6 months of the diagnosis and treatment for Lyme disease.

ACUTE EM (N=40)

  1. Age 18 or older.
  2. EM diagnosed by the study physician.
  3. Receiving antibiotic therapy for Lyme disease for less than 48 hours.

LYME ARTHRITIS (N=40)

  1. Age 18 or older
  2. Lyme arthritis and have not received antibiotic therapy for the disease.

HEALTHY VOLUNTEERS (N=20)

  1. Age 18 or older
  2. No prior history of Lyme disease
  3. Negative whole cell ELISA or C6-based antibody test for Lyme disease

Patients with recently diagnosed (acute) EM (within 48 hours of starting antibiotic therapy) and patients with untreated Lyme arthritis will be recruited in an attempt to increase the chances of finding a positive result by xenodiagnosis (an attempt of a positive control ) While patients with acute untreated EM would be the best positive control group, it would be unethical to withhold therapy in these patients for the few days required for tick feeding, due to the risk of dissemination of the organism and possible morbidity. Patients with untreated Lyme arthritis will be recruited to establish whether xenodiagnosis can be used to identify infection in late stage Lyme patients where the bacterium is known to be present. These patients have been infected for months and will not be harmed for delaying therapy for a few days. Lyme arthritis is a late manifestation of B. burgdorferi infection, and hematogenous dissemination already occurred at this late stage. Studies have shown that the presence or absence of previous antibiotic treatment is more predictive than the duration of untreated arthritis for the success of antibiotic therapy in Lyme arthritis. Similarly, patients who just started therapy for EM may still have live Borrelia in the skin and xenodiagnosis may be able to recover the bacteria (but culture of skin biopsies from patients with EM become negative very quickly - within one dose - on antibiotic therapy).

While treatment for Lyme disease will not be offered under this protocol, it may be available via different clinical research protocols or regular medical care at the study site. If not, treatment will be prescribed by the patient s primary care. For patients with untreated early Lyme disease (erythema migrans), antibiotics can be started at the same day of tick placement. For patients with untreated Lyme arthritis, antibiotics can be started after collection of xenodiagnostic ticks (usually 4-5 days, up to 7 days). For patients with Lyme arthritis, if less than 14 ticks fed successfully and if the participant agrees, antibiotic treatment can be delayed until after the repeat procedure.

Patients with acute EM and untreated Lyme arthritis will be able to re-enroll as Patients with Lyme disease, post-therapy. Therefore, in case of positive results, we will be able to compare between the procedures.

Negative control patients will include healthy volunteers from Lyme endemic areas who have never been diagnosed with Lyme disease and have a negative B. burgdorferi ELISA and C6 antibody titer.

EXCLUSION CRITERIA

  1. No antibiotic therapy active against Lyme disease in the previous 3 months (except patients with acute EM).
  2. History of allergy to surgical tape or dressing.
  3. History of severe reactions to tick bites (granuloma or systemic reactions).
  4. Inability to maintain the dressing for any reason.
  5. Pregnancy or lactation.
  6. Unwillingness to use an effective method of birth control for the duration of participation in the study (women of child-bearing potential only) and for at least 3 months following the last tick placement.
  7. Use of investigational therapy and devices during the time of the study and/or in the month prior to signing the informed consent.
  8. Active severe skin disease, uncontrolled diabetes, cancer other than non-melanoma skin cancers, autoimmune disease requiring immunosuppressive therapy, or history of HIV, chronic viral hepatitis, or syphilis.
  9. Oral or IV steroids in the previous 2 weeks (topical, nasal, inhaled, intra-articular, and replacement doses of steroids are not exclusions).
  10. Any other condition that, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in and completing the study.
  11. Refusal to participate in specimen collection and storage for future study related use.

EXCLUSION FROM SKIN BIOPSY PART OF THE PROTOCOL

  1. History of forming large thick scars (keloids) after skin injuries or surgery.
  2. History of excessive bleeding after cuts or procedures.
  3. Currently taking anticoagulants.
  4. History of allergy to lidocaine.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02446626

Contacts
Contact: Adriana R Marques, M.D. (301) 435-7244 lymedxstudies@niaid.nih.gov

Locations
United States, Connecticut
Mansfield Family Practice Recruiting
Storrs, Connecticut, United States, 06268
Contact: Research Team    617-636-5952    LymeStudy@tufts.edu   
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
United States, Massachusetts
Tufts Medical Center 800 Washington St. Recruiting
Boston, Massachusetts, United States, 02111
Contact: Research Team    617-636-5952    LymeStudy@tufts.edu   
United States, New York
New York Medical College Recruiting
Valhalla, New York, United States, 10595
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Adriana R Marques, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02446626     History of Changes
Other Study ID Numbers: 150131  15-I-0131 
Study First Received: May 13, 2015
Last Updated: August 31, 2016
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Lyme Disease
Ixodes scapularis
Borrelia Burgdorferi
Post treatment
Infection

Additional relevant MeSH terms:
Lyme Disease
Borrelia Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Tick-Borne Diseases
Spirochaetales Infections
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 29, 2016