This study is NOT currently recruiting participants.
Number
15-I-0131
Sponsoring Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Children
Keywords
Lyme Disease; Ixodes scapularis; Borrelia Burgdorferi; Post treatment; Infection
Recruitment Keyword(s)
None
Condition(s)
Lyme Disease
Investigational Drug(s)
Investigational Device(s)
Lyme disease xenodiagnosis
Intervention(s)
Procedure/Surgery: Skin biopsy Procedure/Surgery: Blood draw Device: Xenodiagnosis
Supporting Site
National Institute of Allergy and Infectious Diseases
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.
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.
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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 13 months, fulfilling the case definition of confirmed or probable Lyme disease by the US Centers for Disease Control and Prevention (CDC) (https://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/). 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 (https://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/). 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 enzyme-linked immunosorbent assay (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). Prophylaxis with a single dose of doxycycline 200 mg is not an exclusion. 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.
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 13 months, fulfilling the case definition of confirmed or probable Lyme disease by the US Centers for Disease Control and Prevention (CDC) (https://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/).
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 (https://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/).
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)
2. EM diagnosed by the study physician.
3. Receiving antibiotic therapy for Lyme disease for less than 48 hours.
LYME ARTHRITIS (N=40)
2. Lyme arthritis and have not received antibiotic therapy for the disease.
HEALTHY VOLUNTEERS (N=20)
2. No prior history of Lyme disease.
3. Negative whole cell enzyme-linked immunosorbent assay (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). Prophylaxis with a single dose of doxycycline 200 mg is not an exclusion.
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.
Principal Investigator
Referral Contact
For more information: