Re: Some Interesting Materials on the NIH Study

a_weisman_at_yahoo.com
Date: 01/10/05 

Date: 10 Jan 2005 07:13:38 -0800

PART 4, Carl Brenner "explains" the Study:

Chronic Lyme Treatment Study Web site, New York Medical College
http://www.nymc.edu/lyme

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Other information on the NIH chronic Lyme disease study:

NIH Chronic Lyme Study

An Explanation by Carl Brenner

Although significant advances in Lyme disease research have occurred
over the last two decades, little progress has been made in
understanding the etiology of and proper treatment for chronic Lyme
disease symptoms. Are lingering symptoms after "appropriate" antibiotic

therapy due to persistent infection, a derangement of the immune
system,
slowly resolving disease or permanent tissue damage? Is it
possible that these phenomena occur in combination in some patients?
The answers to these questions have profound implications for the
treatment of chronic Lyme disease; therefore, it is important that they

be aggressively pursued. Unfortunately, this is a research area that
Lyme disease investigators have historically shied away from.

There is hope on the horizon, however. In early 1994, in response to
a directive from Congress, the National Institute of Allergy and
Infectious Diseases (NIAID) convened a workshop on the NIH campus to
review issues relating to chronic Lyme disease. In attendance were
about
a dozen academic Lyme disease researchers, several representatives from

government health agencies and a handful of Lyme disease clinicians and

patient advocates. At the meeting, attendees discussed ways to improve
the diagnosis and treatment of chronic Lyme disease and suggested
specific research directions for future studies of the subject. Later
in
the year, another meeting was held, with additional participants in
attendance, to explore study designs for possible clinical
investigations of chronic Lyme disease.

As an outcome of these consultations, NIAID issued a request for
proposals (RFP) to the academic Lyme disease research community in
1995.
Two research groups responded to the RFP by submitting detailed
proposals for clinical treatment trials of patients with chronic Lyme
disease. Meanwhile, scientists at NIAID began designing an intramural
chronic Lyme study of their own, to be carried out on the NIH campus.
(This study has already begun.) Finally, in 1996 a contract was awarded

to Tufts/New England Medical Center -- one of the two groups that
responded to the RFP - to initiate an extramural study of patients with

chronic symptoms after prior treatment for Lyme disease. Thus, the
current "NIAID Chronic Lyme Disease Study" comprises two parts, one
intramural and one extramural.

The focus of the intramural study is on patients with chronic Lyme
disease of the nervous system. Patients with neurologic infection will
be rigorously tested and compared with five control groups: Lyme
arthritis patients, patients with multiple sclerosis, recovered Lyme
disease patients, asymptomatic individuals who are seropositive for
antibodies to B. burgdoreri, and finally, a group of healthy
volunteers. The test battery is extremely comprehensive, and includes a

complete blood workup, neurologic exam, neuropsychological testing,
EKG,
brain MRI, nerve conduction studies (if appropriate), HLA typing, blood

lymphocyte typing, blood cytokine profiles and lumbar puncture. Spinal
fluid from all patients, including the controls, will be probed for
borrelial antigens, DNA and immune complexes, as well as other, more
routine CSF parameters. By examining the entire study population
clinically, microbiologically and immunologically, NIAID investigators
hope to compile a prospective database upon which state-of-the-art
diagnostic criteria for Lyme disease can be established. In addition,
patients with active Lyme disease will be offered treatment through
their primary care physician, and will be evaluated at NIAID at
periodic
intervals thereafter.

The extramural study will focus on a different patient population.
Although objective manifestations of Lyme disease usually resolve after

antibiotic treatment, it is well recognized that a significant
percentage of patients continue to suffer from persistent symptoms such

as musculoskeletal pain, fatigue, memory impairment, numbness and
tingling despite "appropriate" antibiotic therapy. Considerable
controversy exists over whether these symptoms are due to persistent
infection with B. burgdorferi, and if so, whether they are responsive
to
additional treatment. In the extramural portion of the Chronic Lyme
Study, patients with these manifestations of chronic Lyme disease after

previous treatment will be enrolled in a double-blind
placebo-controlled
trial of the efficacy (and safety) of three months of additional
antibiotic therapy. The antibiotic regimen selected by the
investigators
is intravenous ceftriaxone (2 grams a day) for one month, followed by
oral doxycycline (200 mg/day, given in doses of 100 mg every 12 hours)
for two months.

In a placebo-controlled study, patients are randomized in a 1:1
ratio to receive either active drug or placebo. Thus, half the patients

in this study will receive antibiotic and half will receive dummy
medications that are usually indistinguishable from the real thing.
Because the study is double-blinded, neither the patients nor the
investigators will know which patients are getting what. This will
insure that the results of the study are unaffected by physician or
patient expectations. The primary outcome measure will be the patients'

own self-ratings six months after the initiation of treatment on a
frequently employed, previously validated, written health survey form.
Having patients rate themselves is another important tool for
eliminating possible physician bias in evaluating patient progress, or
lack thereof.

During the period during which either antibiotics or placebo are
being administered, the study scientists will collect multiple blood
and
urine specimens from patients for repeated probes for borrelial DNA by
PCR (in blood) and borrelial antigens (in urine). In addition, all
patients will be screened for possible co-infection by other tick-borne

pathogens, such as ehrlichia and babesia. Finally, neuropsychological
testing will be employed on all patients in the study, both before and
after treatment, to provide measures of immediate and delayed memory,
conceptualization, language and attention. All of these measurements
will supplement the patient self-ratings and will provide data for
correlating patient progress with objective measures of infection or
cognitive improvement.

One particularly attractive facet of the extramural study is that
it will examine both seropositive and seronegative patients.
(Statistics
on the two groups will be compiled separately.) Since it is well known
that antibiotic treatment can abrogate the human antibody response, and

since all of the patients enrolled in the study will have previously
received antibiotics for their Lyme disease, it is clear that it would
be both arbitrary and misguided to exclude patients based on the
absence
of antibodies to B. burgdoreri in their blood.

The objectives of the extramural study, then, are as follows:

1.to determine whether three months of additional antibiotic therapy
benefits patients with chronic Lyme disease.
2.to determine if evidence of persistent infection with B. burgdorferi

can be found in patients with chronic Lyme disease.
3.to determine if evidence of co-infection with other tick-borne
agents
can be found in these patients.
4.to see if specific clinical or laboratory parameters improve in
patients who receive antibiotics compared to patients who receive
placebo.
5.to determine if specific parameters are predictive of a response to
therapy should it be observed.

Taken together, the intramural and extramural portions of the
Chronic Lyme Study constitute a reasonable, if somewhat belated, start
on the investigation of the various challenges presented by chronic
Lyme
disease. The exhaustive testing regimen of the intramural study should
yield exciting data, particularly in the immunogenetic realm, and the
extramural study's focus on patients with post-treatment symptoms (a
population that has been badly neglected up to now) is very welcome. In

addition, the two studies complement each other in that one focuses on
patients with clear-cut infection while the other examines a population

whose infectious status is unknown. Finally, currently-proposed but not

yet funded studies of non-human primates will further supplement data
gathered during these projects, in that they will allow researchers to
have access to tissue for extensive pathology studies, and thus aid in
the possible discovery of post-treatment sanctuaries for B. burgdoreri
in a primate model. While no single study or group of studies is going
to definitively solve all of the issues surrounding chronic Lyme
disease, it is hoped that these projects will at least kick start the
process.

Last revised November 28th, 1998
http://www.lymealliance.org/Medical/MedCategory6/Med22/med22.html

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