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

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.

- 96INCLUSION 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 acute or chronic
Lyme disease and negative western blot to B.burgdorferi in the serum 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 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.