A Comprehensive Clinical, Microbiological and Immunological Assessment of Patients With Suspected Post Treatment Lyme Disease Syndrome and Selected Control Populations

Study Purpose

This study will determine whether patients who have been infected with the Lyme bacteria, Borrelia burgdorferi, and treated with antibiotics still have the bacteria alive inside them and whether it is causing their symptoms. The information from this study may serve as a basis for developing stringent diagnostic criteria for Lyme disease and the establishment of future treatment trials. Individuals in the following categories may be eligible for this study: chronic Lyme disease; chronic Lyme arthritis; seropositive control (are infected with the bacteria that causes Lyme disease but do not have disease symptoms); recovered control (have been sick with Lyme disease but were treated successfully and are currently well); control with multiple sclerosis (patients with multiple sclerosis); and healthy volunteers. Patients in the chronic Lyme disease category must be age 13 and above; all others must be age18 and above. Candidates will be screened with blood and urine tests. Participants will have a physical examination and the following tests: Blood tests Includes HLA-typing, a genetic test of immune system markers; Leukapheresis Collection of large numbers of white blood cells Whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are removed and the rest of the blood is returned to the body, either through the same needle used to draw the blood or through another needle in the other arm. (Alternatively, patients will 100 cc (about 7 tablespoons) of blood drawn.); Lumbar puncture (spinal tap) Collection of cerebrospinal fluid (CSF, fluid that bathes the brain and spinal cord). A local anesthetic is administered and a needle is inserted in the space between the bones in the lower back where the cerebrospinal fluid circulates below the spinal cord. A small amount of fluid is collected through the needle; Magnetic resonance imaging (MRI) of the brain Imaging of the brain using a strong magnetic field and radio waves instead of X-rays. During the scan, the patient lies on a table in a narrow cylinder containing a magnetic field. He or she can speak with a staff member via an intercom at all times during the procedure; Neuropsychologic testing; Some participants may also have a hearing test and urine collection. Participants whose test results are positive for Borrelia burgdorferi will be followed at NIH at intervals of 3 to 6 months until it is determined whether there is infection. Those who are infected will be offered treatment with the antibiotic ceftriaxone. Following treatment, patients will return to the NIH Clinical Center for follow-up visits 1 week after treatment and again at 3, 6 and 12 months. The lumbar puncture, hearing examination, blood and urine tests will be repeated at these visits to evaluate the response to treatment, and the leukapheresis will be repeated for research purposes. Patients whose MRI was abnormal during therapy will have a repeat MRI at the 3-month, 6-month and 1-year visits. All participants with chronic Lyme disease, chronic Lyme arthritis, seropositive controls and recovered controls may be reevaluated at intervals of 6 to 12 months.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Yes
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 13 Years and Over
Gender All
More Inclusion & Exclusion Criteria

  • -

    INCLUSION CRITERIA:

    Screening: Age greater than or equal to 13 years old, suspect of suffering from Lyme disease Post-Treatment Lyme Disease Syndrome (PTLDS): For the purposes of this study, PTLDS is defined as occurring in male or female patients age 13 and above who have been diagnosed with confirmed or probable Lyme disease per CDC definition (https://wwwn.
cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/). Studyphysician will review history to confirm probable cases. They have received recommended antibiotic therapy and have persistent or relapsing symptoms and/or signs for at least six months after therapy. They also should have no other documented explanation for their signs and symptoms. Lyme arthritis controls: For the purposes of this study, Lyme arthritis is defined as occurring in an otherwise healthy male or female aged 18 and above who have intermittent episodes of arthritis involving one or few joint, without any other cause being documented, and have positive serum antibodies to B.burgdorferi confirmed by Western blot according to the CDC criteria. Recovered Controls: For the purposes of this study, a recovered control is defined as an otherwise healthy male or female aged 18 and above who has had Lyme disease, fulfilling the CDC Lyme Disease National Surveillance Case Definition and who had received accepted antibiotic treatment for Lyme disease (at least 3 months since the end of antibiotic therapy before protocol evaluation) and who are currently asymptomatic. Seropositive Controls: For the purposes of this study, a serpositive control is defined as an otherwise healthy male or female aged 18 and above who has positive serum IgG antibody to B.burgdorferi by Western blot according to the CDC criteria and are asymptomatic and who recall no episodes of disease compatible with Lyme infection and have not received antibiotic therapy for Lyme disease. OspA vaccinated control: For the purposes of this study, a OspA vaccinated control is defined as an otherwise healthy male or female aged 18 and above who has received at least two doses of the OspA vaccine for Lyme disease (Lymerix [R]). These controls may have a positive ELISA for B.burgdorferi but a negative (or unreadable) IgG western blot. Multiple sclerosis controls: For the purposes of this study, a multiple sclerosis control is defined as an otherwise healthy male or female aged 18 and above with relapsing-remitting or progressive multiple sclerosis as defined by the Clinical Trial Committee of the National Multiple Sclerosis Society and no evidence of prior exposure to B.burgdorferi as indicate by negative history for Lyme disease and negative Western blot for B.burgdorferi in the serum by the CDC criteria. Patients should have a Kurtzke or Expanded Disability Status Scale (EDSS) between 1 to 5. Healthy Volunteers: For the purpose of this study, a healthy volunteer is defined as healthy male or female, age 18 and above, with no history compatible with Lyme disease and negative serological testing to B.burgdorferi by the CDC criteria. All study participants must agree to allow their samples to be used for future research.

EXCLUSION CRITERIA:

General

exclusion criteria:

Age less than 18 (less than 13 for patients with PTLDS). Weight less than 70 Lb (35 kg). Pregnancy or lactation. Women with childbearing potential who are sexually active with a male partner and unwilling to use effective contraception during the evaluation and treatment phases of the protocol. Clinically significant laboratory abnormalities including positive test for syphilis (RPR), HBsAg, anti-HCV, anti-HIV. Chronic medication use will be evaluated in a case-by-case basis. Not able to understand all of the requirements of the study or unable to give informed consent and/or comply with all aspects of the evaluation. EXCLUSION CRITERIA FOR PTLDS PATIENTS AND LYME ARTHRITIS CONTROLS: In addition to the general exclusion criteria, these individuals will be excluded for: 1. Use of immunosuppressive drugs such as systemic (but not topical or inhalant) steroids and cytotoxic agents. 2. History of any recognized autoimmune disease such as rheumatoid arthritis, vasculitis, systemic erythematous lupus, etc. 3. Serious pre-existing or concurrent chronic medical or psychiatric illnesses other than Lyme disease. 4. Past history of significant head trauma, alcohol or substance abuse in the past 5 years or other medical illness that might produce neurologic deficit (such as cerebrovascular disease). 5. Use of systemic antibiotics in the previous month. 6. Use of immunomodulators such as interferons. 7. Chronic medication use will be evaluated in a case-by-case basis. 8. Patients will be excluded from this protocol if they are judged by the principal investigator as having a significant impairment in their capacity for judgment and reasoning that compromise their ability to make decisions in their best interest. EXCLUSION CRITERIA FOR RECOVERED, SEROPOSITIVE, OSPA VACCINATED AND HEALTHY VOLUNTEERS CONTROLS: In addition to the above applicable exclusion criteria (general exclusion criteria and exclusion criteria for PTLDS patients and Lyme arthritis controls), these individuals will be excluded for: 1. Pre-existing or concurrent serious chronic medical or psychiatric illness. EXCLUSION CRITERIA FOR MULTIPLE SCLEROSIS CONTROLS: In addition to the above general exclusion criteria, these individuals will be excluded for: 1. Pre-existing or concurrent serious psychiatric or chronic medical illness besides Multiple Sclerosis. 2. Past history of significant head trauma, alcohol or substance abuse in the past 5 years or other medical illness, besides Multiple Sclerosis, that might produce neurologic deficit (such as cerebrovascular disease). 3. Previously received total lymphoid irradiation (TLI) or cladribine. 4. Has used of immunoactive medications (excluding beta-interferon) in the three months preceding the study. 5. In the three months prior to the study initiation, was given such investigational treatments as plasmapheresis, hyperbaric oxygen, gangliosides, Copolymer 1, etc.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00001539
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Adriana R Marques, M.D.
Principal Investigator Affiliation National Institute of Allergy and Infectious Diseases (NIAID)
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

NIH
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Lyme Disease
Study Website: View Trial Website
Additional Details

Lyme disease has emerged as the leading vector-borne disease in the United States. Despite how much has been learned about Lyme borreliosis in the past decade, there are still many remaining areas of uncertainty. One fundamental question is whether persistent signs and symptoms of disease, despite the administration of what is currently considered to be adequate antibiotic therapy, are due to ongoing active borrelial infection, to a post-infectious syndrome, to irreversible sequelae of earlier tissue injury or due to a condition unrelated to Lyme disease. Reliable objective markers of infection, of clinical status and of host responses to the organism are required to discern the scope and the implications of persistent borrelial infection, the effectiveness of current treatment options, and the development of new therapeutic approaches. The goal of this study is to assemble and follow a well-characterized cohort of patients with post-treatment Lyme disease syndrome and relevant controls that will yield a prospective database upon which stringent diagnostic criteria can be established and future therapeutic trials can be designed.

Arms & Interventions

Arms

: Healthy volunteers

healthy individuals who have never had Lyme disease

: Lyme Arthritis

patients with suspected Lyme arthritis

: Multiple sclerosis controls

patients diagnosed with multiple sclerosis who have never been diagnosed with Lyme disease

: OspA vaccine

patients who received two doses of the OspA vaccine

: PTLDS

patients with presumed PTLDS

: PTLDS for screening

patients suspected of PTLDS for screening

: Recovered controls

patients who were diagnosed with Lyme disease, treated, and fully recovered

: Seropositive controls

patients who are seropositive for Lyme disease, but have no manifestations/symptoms and have never been treated for Lyme disease

Interventions

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Bethesda, Maryland

Status

Recruiting

Address

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892

Site Contact

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

prpl@cc.nih.gov

800-411-1222 #TTY8664111010