Re: Some Interesting Materials on the NIH Study

a_weisman_at_yahoo.com
Date: 01/10/05 

Date: 10 Jan 2005 07:09:32 -0800

PART 1

http://www.geocities.com/HotSprings/Oasis/6455/nih-study-complete.txt

NIH chronic Lyme disease study information on internet - complete file
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as of 22 June
1999

Basic information on the NIH chronic Lyme disease study:

NIAID's Chronic Lyme Disease Study

Questions and Answers

In 1996, the National Institute of Allergy and
Infectious Diseases (NIAID) awarded a five-year contract
to the New England Medical Center (NEMC) to study how
chronic Lyme disease develops and how to improve its
treatment. This document answers general questions about
these studies. It is important to keep in mind that this
is a research project, designed to help scientists
better understand Lyme disease, and to improve ways of
diagnosing and treating this disease. Anyone with more
specific questions not addressed in this document is
encouraged to call the NEMC Lyme Disease Center at
1-888-596-3287.

Q1: Why is NIAID funding this study?

Although scientists have identified Borrelia burgdorferi
as the bacterium that causes Lyme disease, we need to
know much more about how it causes disease. Many
questions remain about the chronic manifestations of
Lyme disease. The question is not whether such a
syndrome exists; rather, it is how B. burgdorferi
elicits so many different long-term problems in some
people.

Currently, it is not known whether the symptoms
associated with chronic Lyme disease are caused by one
or more of the following: 1) an ongoing (persistent)
infection with B. burgdorferi or other tick-borne
pathogen; 2) reinfection with B. burgdorferi; 3) an
autoimmune or inflammatory response associated with the
initial infection; or 4) some other mechanism. Although
the symptoms associated with chronic Lyme disease may
result from persistent infection with B. burgdorferi,
direct evidence of persistent infection usually is not
found. Consequently, it is difficult for physicians to
decide which treatment strategies are most effective.

For example:

* What types of antibiotics should be used?
* How long should they be taken?
* If beneficial effects occur, how long do they last?
* Should drugs other than antibiotics be tested?
* What outcomes can be used to determine that a given
course of antibiotic treatment is indeed effective?

This project is examining many of these questions in a
stepwise and systematic manner. The research involves
conducting a variety of laboratory tests, many not used
before in patients with chronic Lyme disease, to
characterize the disease in detail. The study also will
determine the antibiotic approaches and monitoring
techniques likely to prove most useful to doctors
treating people with chronic Lyme disease.

Q2: Who are the study researchers?

Dr. Mark Klempner of the New England Medical Center
heads the project. Dr. Klempner, together with the NIAID
project officer, Dr. Phillip Baker, are responsible for
the overall design and conduct of the studies performed
under the contract. Dr. Arthur Weinstein coordinates all
aspects of the study at Westchester County Medical
Center/New York Medical College. Dr. Gary Wormser, also
at New York Medical College, oversees the administration
of study medications. In this role, he works closely
with the nursing staff to minimize any adverse reactions
to antibiotics and to reduce the risk of bacterial
infections sometimes associated with prolonged
intravenous therapy. He also cultures spinal fluid
samples to look for the presence of viable B.
burgdorferi. Dr. Jesse Goodman, University of Minnesota
School of Medicine, conducts all laboratory tests to
detect possible co-infecting agents (ehrlichia and
babesia). Dr. Allen Steere of Tufts University oversees
the serologic tests on patient blood samples. All these
investigators are experts in their fields.

Q3: How were the contract proposals reviewed and
evaluated?

A panel of non-NIH scientists reviewed and evaluated the
contract proposals, ranking them according to scientific
merit, the chief criterion considered in awarding a
contract. The projected cost of carrying out the
required work was another important factor considered. A
contract proposal must provide evidence that the
investigators can meet the scientific objectives
established by the Institute. Thus, the review panel
evaluated both the scientific expertise and the
soundness of the experimental design of the
applications. A sample protocol primarily enables the
scientific reviewers to assess the scientific capability
and research approach of the applicants. NIAID staff
work closely with contract investigators at every step
to refine the design of the treatment protocol so the
studies achieve the defined objectives.

Q4: Are clinical trials part of this research project?

Yes, Phase III clinical studies to determine the
effectiveness of a treatment are a major component of
this project. These multicenter studies are being
conducted in collaboration with scientists in NIAID's
intramural research program in Bethesda and with other
scientists elsewhere. The goal is to further
characterize chronic Lyme disease so that rational, more
effective therapies can be devised.

These studies are double-blinded and placebo-controlled.
That means all specimens to be tested are coded so that
neither the investigators nor the patients know who is
getting antibiotic and who is receiving placebo. Only
after the study has been completed and all specimens
have been analyzed will the codes be broken so the
effectiveness of treatment can be evaluated. Such an
approach ensures objectivity and rules out any possible
bias or preconceived ideas about any aspect of the
studies. Biostatisticians review the study protocols to
determine how many patients must be enrolled to obtain
conclusive, statistically meaningful results.

Q5: Who is overseeing the research?

Dr. Phillip Baker, the NIAID project officer, has final
approval of all studies that are undertaken. As with all
Phase III clinical studies, an independent Data and
Safety Monitoring Board (DSMB) -- appointed by the
National Institutes of Health (NIH) -- regularly
evaluates the results obtained. In addition, NIAID has
established an advisory body made up of research
scientists, medical experts and members of Lyme disease
patient advocacy groups to help define the issues to be
addressed and to resolve any problems that may arise
during the course of these studies.

Q6: How do the NEMC studies relate to the NIAID clinical
trial conducted at the NIH?

NEMC researchers work closely with NIAID intramural
investigators, although the criteria for selecting
patients for each study are different. In the NEMC
studies, patients must have had a documented case of
acute Lyme disease, have received treatment and
recovered, but subsequently have developed all the signs
and symptoms associated with chronic Lyme disease. In
contrast, patients enrolled in the intramural studies
are more likely to be actively infected based on the
results of a variety of laboratory tests. Additionally,
the NEMC studies have a placebo arm, whereas all
patients in the intramural studies receive an
antibiotic. The intramural study patients receive
antibiotics because they are most likely to be actively
infected, and therefore it would be unethical to give
any of them a placebo.

Together, the investigators in the two studies will
determine if the immunologic and diagnostic tests used
to monitor the effectiveness of antibiotic therapy prove
useful for some or all of the patients in the study. The
studies are employing experimental tests not currently
available to physicians, and NIAID staff hope that these
tests will provide valuable insights into chronic Lyme
disease and help doctors evaluate the effectiveness of
antibiotic treatment.

Q7: People in the intramural studies must have a
positive Lyme antibody test and Western blot. Do the
NEMC studies also require such tests, even though some
people with symptoms of chronic Lyme disease are
seronegative?

These antibody tests are used in the initial diagnosis
of early or acute Lyme disease, the major population
selected for enrollment in the intramural studies.
Although the patients in the intramural studies must
have positive ELISA and Western blot tests, indicating
the presence of B. burgdorferi antibodies, patients in
the NEMC studies, who have chronic Lyme disease, are
divided into two groups (seropositive and seronegative),
and thus do not have to be antibody-positive at the time
of enrollment. However, they must be able to document
that they have been diagnosed with Lyme disease in the
past.

Q8: Previously I had a positive Western blot test for
Lyme disease. Why am I required to currently test
positive by Western blot to enroll in the seropositive
group?

Because the reliability and reproducibility of blood
tests for Lyme disease are somewhat controversial,
requiring a current positive Western blot ensures that
all the patients in the study will have a standardized
blood test done under the same conditions and within the
same timeframe. If screening tests indicate that a
volunteer is seropositive, he or she can be admitted to
the seropositive group or arm of the study. Seronegative
patients can participate in the study, too; however,
they are enrolled in the seronegative group. Both groups
receive the same treatment.

Q9: Why are patients who test positive by polymerase
chain reaction (PCR) for B. burgdorferi at the time of
initial evaluation being excluded from the study?

After enrollment, patients are selected at random for
assignment to either the placebo or antibiotic treatment
group. Patients who test positive for B. burgdorferi by
PCR are considered to be actively infected. Thus, these
patients are excluded from the NEMC placebo-controlled
study to avoid the possibility that they will be
selected at random to receive placebo instead of
treatment. Such patients are referred to the NIAID
intramural study on Lyme disease, which has no placebo
group; there, all patients are treated with an
antibiotic since multiple tests (including PCR) indicate
that they are probably actively infected.

Q10: The enrollment criteria state, "Persons who have
serious pre-existing or concurrent chronic medical or
psychiatric illnesses are excluded from the study." What
types of psychiatric illnesses does this include? If I
have been diagnosed with depression, would that exclude
me from the study?

Questions like this can best be handled on a
case-by-case basis and should be referred to the
investigators of the study. Our goal is to enroll a
group of patients in whom the therapy used can be
evaluated unequivocally. This would be difficult, if not
impossible, to do if patients have more than one
diagnosis that could account for some of their symptoms.

Q11: Why is there a placebo group in the study?

Patients given placebo often appear to improve by as
much as 30 to 40 percent. Although the basis for this
"placebo effect" is not known, it is important to
include a placebo group to ensure that the beneficial
effects of any treatment under study are significantly
greater than what can be attributed to the placebo
effect alone. Patients are not given placebo if there is
direct evidence of active infection or if there is
reason to believe that their condition would worsen if
they are not treated.

Q12: The Lyme Urine Antigen Test (LUAT) has been
included in the study. Does that mean that the test is
generally seen as valid?

The NIAID Lyme Disease Advisory Panel requested that the
LUAT be included in the study to gather information on
the test's utility. Its inclusion in the study does not
imply endorsement of LUAT, which has not been approved
by the FDA as a valid diagnostic test for Lyme disease.
Rather, an important aspect of the study is evaluating
the utility of both new and old tests in the diagnosis
and management of patients with Lyme disease.

Q13: Why must patients enrolled in the study have a
lumbar puncture (spinal tap)?

Because the symptoms associated with chronic Lyme
disease are mainly neurologic, there is reason to
believe it may result from a persistent infection of the
nervous system. Therefore, laboratory tests performed on
samples of cerebrospinal fluid (CSF), which are obtained
by lumbar puncture, provide a means to look for
abnormalities that can be associated with central
nervous system disorders.

Q14: Why does the study have only a single treatment
option? Why not include intravenous treatment at
differing time intervals – say 4, 6 and 8 weeks?

The inclusion of multiple time intervals or different
antibiotics, for that matter, would require
substantially more patients to be enrolled in the study,
and would exceed the allotted study budget. Should the
12 week treatment being evaluated be found to be
beneficial, future studies can be designed to test the
effectiveness of shorter intervals using either the same
or different combinations of antibiotics.

Q15: Are patients reimbursed for travel expenses to
reach the study sites?

Our goal is to facilitate easy transportation to and
from the study sites. Free parking is provided, and
through a close working relationship with several travel
agencies, access to study sites is made as easy as
possible. More specific questions concerning
reimbursement for expenses should be addressed to the
principal investigators associated with the studies.

Q16: Who will have access to my medical records and the
name of my physician?

All medical records will be strictly confidential and
will be available only to those directly involved in the
study. They will be used only for purposes related to
the study.

Q17: How much longer will the study continue?

The study will continue until the required numbers of
patients have been enrolled and treated, and until all
necessary visits to evaluate the efficacy of therapy
have been completed. At the current rate of enrollment,
it is expected to take approximately three more years to
complete the study.

Q18: When will results of the study be available?

After the study has been completed and all the data have
been analyzed, we anticipate publishing the results in a
peer-reviewed scientific journal and elsewhere. We will
also make the information available on the NIAID Web
site (www.niaid.nih.gov).

Relevant Pages

  • Re: Controlled trial ABX persistant lyme
    ... The study was a retreatment study, in which patients were treated ... > term study as the treatment in the study was not long term, ... Brain Imaging and Retreatment Study of Persistent ... Lyme Disease ...
    (sci.med.diseases.lyme)
  • Re: NIH Intramural Study
    ... patients with persistent symptoms and a history of Lyme borreliosis. ... reproduces an invariable region of the VlsE lipoprotein of Borrelia ... outcome in a population of patients with post-treatment Lyme disease ... binding proteins of the Borrelia burgdorferi oligopeptide permease ...
    (sci.med.diseases.lyme)
  • Donta: Tetracycline therapy for chronic Lyme disease (1997)
    ... Tetracycline therapy for chronic Lyme disease. ... Two hundred seventy-seven patients with chronic Lyme disease were ... Improvement frequently did not take place for several weeks; after 2 months of treatment, 33% of the patients' conditions were significantly improved, and after 3 months of treatment, 61% of the patients' conditions were significantly improved. ...
    (sci.med.diseases.lyme)
  • pt.2 JAMA - A 58-Year-Old Man With a Diagnosis of Chronic Lyme Disease
    ... What is the epidemiology of Lyme disease? ... When taking antibiotics he felt progressively better, ... In the Northeast and North Central United States, the infection is ... In untreated patients, Lyme disease usually occurs in stages, with different ...
    (sci.med.diseases.lyme)
  • Re: All the Major Dirt on Lyme, except the FRAUD in testing
    ... evoked potentials were obtained from 12 patients with active CNS Lyme ... disease patients and in 54% of the post CNS Lyme disease patients. ... Steere, Sigal, Rahn and Schoen report treatment failure in 1/2 the ...
    (sci.med.diseases.lyme)