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

NCT00001539 | Recruiting

• 2 other identifiers: 96005296-I-0052
• Study Type: observational
• Target: 700
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lyme Disease

Keywords

Borrelia Burgdorferi; Lyme Borreliosis; Tick-Borne Disease; Natural History; Lyme Disease

Outcome Measures

Primary Outcomes (1)

• Assemble and follow a well-characterized cohort of patients with post-treatment Lyme disease syndrome and relevant controls

  This protocol serves as the basis for multiple parallel lines of investigation in different aspects of Lyme disease and PTLDS. The formation of the cohort and follow up are the main outcomes.

  duration of the study

Secondary Outcomes (4)

• Explore biological markers of B. burgdorferi infection and PTLDS

  duration of study

• Development of new tests for Lyme disease and PTLDS

  duration of study

• Assessment of the immunological response in patients with PTLDS

  duration of study

• Assessment of clinical course and outcomes of patients with PTLDS

  duration of study

Study Arms (8)

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

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

Eligibility Criteria

• Age: 13 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Primary clinical

You may qualify if:

• SCREENING FOR SUSPECTED PTLDS
• Age \>= 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 (1) occurring in male or female patients aged 13 and above (2) who have been diagnosed with confirmed or probable Lyme disease per CDC definition (https://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/). Study physician will review history to confirm probable cases. (3) They have received recommended antibiotic therapy (4) and have persistent or relapsing symptoms and/or signs for at least six months after therapy \[4, 5\]. (5) 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 joints, without any other cause being documented, and have positive serum antibodies to B. burgdorferi confirmed by IgG 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 confirmed or probable Lyme disease, fulfilling the CDC Lyme Disease National Surveillance Case Definition (appendix 5), and who had received accepted antibiotic treatment for Lyme disease \[5\] (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 seropositive control is defined as an otherwise healthy male or female aged 18 and above who has positive serum IgG antibody response 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, an OspA vaccinated control is defined as an otherwise healthy male or female age 18 and above who has received at least two doses of the OspA vaccine for Lyme disease (Lymerix ). 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 and 5.

You may not qualify if:

• 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.
• All study participants must agree to allow their samples to be used for future research.
• Use of immunosuppressive drugs such as systemic (but not topical or inhalant) steroids and cytotoxic agents.
• History of any recognized autoimmune disease such as rheumatoid arthritis, vasculitis, systemic erythematous lupus, etc.
• Serious pre-existing or concurrent chronic medical or psychiatric illnesses other than Lyme disease.
• 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).
• Use of systemic antibiotics in the previous month.
• Use of immunomodulators such as interferons.
• Chronic medication use will be evaluated in a case-by-case basis

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (1)

• Marques AR, Yang X, Smith AA, Zhuang X, Turk SP, Williams CD, Law MA, Barbour AG, Pal U. Citrate Anticoagulant Improves the Sensitivity of Borreliella (Borrelia) burgdorferi Plasma Culture. J Clin Microbiol. 2017 Nov;55(11):3297-3299. doi: 10.1128/JCM.01046-17. Epub 2017 Sep 6. No abstract available.

  PMID: 28878005 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lyme Disease; Tick-Borne Diseases

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Borrelia Infections; Spirochaetales Infections; Vector Borne Diseases

Study Officials

• Adriana R Marques, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ashley M Thomas

CONTACT

(240) 656-5458; ashley.thomas2@nih.gov

Adriana R Marques, M.D.

CONTACT

(301) 435-7244; amarques@niaid.nih.gov

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: June 13, 1996
• Last Updated: May 1, 2026

Record last verified: 2025-11-06

Locations

US (1)