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

  • participants needed
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 19 September 2021
antibiotic therapy
spinal cord
genetic test
enzyme-linked immunosorbent assay
chronic lyme disease
post-treatment lyme disease syndrome
ospa vaccine


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.



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.

Condition Lyme Disease, Lyme Disease Vaccine
Clinical Study IdentifierNCT00001539
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on19 September 2021


Yes No Not Sure

Inclusion Criteria

Age greater than or equal to 13 years old, suspect of suffering from Lyme
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
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

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
In addition to the general exclusion criteria, these individuals will be
excluded for
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
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
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
Pre-existing or concurrent serious chronic medical or psychiatric illness
In addition to the above general exclusion criteria, these individuals will be
Pre-existing or concurrent serious psychiatric or chronic medical illness besides Multiple Sclerosis
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)
Previously received total lymphoid irradiation (TLI) or cladribine
Has used of immunoactive medications (excluding beta-interferon) in the three months preceding the study
In the three months prior to the study initiation, was given such investigational treatments as plasmapheresis, hyperbaric oxygen, gangliosides, Copolymer 1, etc
Children: Children 13 years and older are eligible to participate in the PTLDS
cohort because the condition under study can affect children. T, and this age
was selected as appropriate for the children to provide assent to and comply
with the study procedures. Children younger than 13 will be excluded from the
PTLDS cohort, and no children will be enrolled in the other study cohorts
Pregnant and lactating women: Pregnant and lactating women are excluded from
study participation. An enrolled participant who becomes pregnant during the
study will be withdrawn
Adults who lack capacity to consent: Adults who lack decision-making capacity
to provide informed consent are excluded at screening, and enrolled adult
participants who permanently lose the ability to consent during study
participation will be withdrawn
NIH staff members: NIH staff may be enrolled if they meet eligibility
criteria. Neither participation nor refusal to participate as a subject in the
research will have an effect, either beneficial or adverse, on the participant
s employment or position at NIH. Every effort will be made to protect
participant information, but such information may be available in medical
records and may be available to authorized users outside of the study team in
both an identifiable and unidentifiable manner
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