Typical Lyme Care Standing on Poor Research
A Brief Look at the Lyme Klempner Study
If you talk to an insurance company clerk who plans to deny coverage or a physician who has not studied Tick-born illness, you might hear them quote the Klempner study on Lyme disease. It is supposed to show Lyme is quickly and easily dispatched no matter how long you have missed diagnosing it.
An independent consulting company, www.verimresearch.com/samples.htm, actually gave the study a "D." And it is used as an example of the poorest of the poor in terms of research quality.
The basics: Klempner et al (2001) gave 4 weeks of IV ceftriaxone followed
by two months of low-dose oral doxycycline or placebo to chronic Lyme
patients with one or more of the following symptoms: musculoskeletal pain,
cognitive impairment, radicular pain, paresthesias or dysesthesias.
The two treatments did not find any significant benefit found in physical or mental health.
Why the Klempner Study is Useless
Why Another Study is the Best to Date
- The Klempner study contains serious methodological flaws. See the ILADS
Position Paper: www.ilads.org/position2.html
- The dose of doxycycline used in the study (200 mg daily) is too low to penetrate the central nervous system--failure was to be expected at this dose. Indeed, many physicians treating patients with positive brain SPECT scans showing Lyme infection quickly ramp up to 600 mg of doxycycline per day. This 200 mg dose is like giving a tiger a cracker and wondering why he is still hungry. I gave this dose to my small poodle when he started biting everyone and was positive on a Lyme test. Dogs seem to have slightly better tests than the poor ones used in humans.
- This was not in actuality a "long-term" trial as described, but really two short-term trials and the second one, the poodle dose of doxycycline, was insufficiently dosed.
- Since patients had failed similar treatment previously, such as these two common antibiotics, what made anyone think a failed treatment would work if repeated?
- Thinking ability was measured only subjectively using patient surveys, making it impossible to assess changes in executive functioning and frontal lobe problems that are so common in chronic Lyme patients.
- Amazingly, the standard in psychiatric thought ability and cognitive neurology, objective neuropsychiatric testing and abilities, was not reported. People just gave self-reports that assume their insight was normal and unaffected by Lyme or other factors.
- Further, Klempner reports not one of 1800 patients screened were PCR positive for Lyme. Despite the many studies and clinical experience showing persistent Lyme infection in ill patients, Klempner could not find one person with Lyme DNA. Even though the DNA PCR test is better done on tissue than blood or urine, it is a way of documenting persisting infection in patients who remain symptomatic after treatment. So he documented that none appeared to still have Lyme? So he either selected his patients with an unusual method with minimal chronic Lyme patients, or the lab doing his PCR's was flawed. Because the authors failed to find, even once, what other researchers have demonstrated repeatedly, doubt is raised as to the accuracy of their PCR methods.
- The antibiotics are assumed to have an added effect. This was not proven or supported.
- The poor dose of doxycycline was only taken 75% of the time! The medication compliance rate was 75%, reducing the doxycycline dose to utterly useless sub-therapeutic levels.
- The is really a short-term ceftriaxone re-treatment study. Many patients had already "failed" treatment with a short course of ceftriaxone, thus making it likely they would do so again.
- People were rejected from the study if they had a positive PCR, which means they had active Lyme DNA in their bodies. They rejected form the study the very patients who may have been most likely to benefit from antibiotics.
- PCR negativity was required to be in the study. Then some had a positive PCR as if it was a new "finding." PCR's are intermittent in chronically ill Lyme patients. The use of this data was peculiar.
- At the beginning of the study, the placebo and antibiotic groups appeared to have significantly different. Specifically, the main outcome measures that were going to be used to see if the antibiotics were useful were different between the groups before any medication was given. These observations may have invalidated the study.
- When one looks at the two groups it is clear there was inadequate patient randomization since pre treatment scores were significantly different.
- Klempner et al. found that over 25% of the enrollees had elevated CSF (spinal fluid) protein. This is hardly a sign of healthy people.
- He also reported that 8 had intrathecal (intra-spinal) production of B. burgdorferi antibodies. These antibodies and/or proteins with their Lyme infection histories, is consistent with a neurological Lyme infection.
- The findings were highly filtered and objective neuropsychological tests were done but left out of the paper and lab results were left out. For example, Klempner replied that the enrollees were given an "extensive battery of neurocognitive tests in addition to the subjective self evaluations of the SF-36. Klempner also publicly alluded to his testing for CSF matrix metalloproteinases in these patients. These can be altered in Lyme patients. Where are the rest of the objective neuropsychological results and the matrix metalloproteinases?
- What other data collected during this study was excluded from his publication? A publication that is often quoted as being "evidence" one should not use antibiotic treatment over a month.
- The study does not discuss the routine reaction of Lyme to antibiotics in which the patient feels worse as the Lyme dies--Jarisch-Herxheimer reactions. Both spirochete illnesses, syphilis and Lyme disease, frequently cause this symptom intensification due to antibiotics. Yet this was fully ignored! Any assessment of how a patient is reporting they feel will be strongly effected by this reaction, and those with active Lyme infection and worsening symptoms due to Jarisch-Herxheimer reactions could prompt their withdrawal from the study.
- The authors appear grossly clueless about the various forms of Lyme. This infection survives in many different forms, which are not die-off debris, but forms with different structures that can revert to still other active structures. In the presence of a hostile mammal immune system, Lyme forms include L-forms, spheroplasts, cystic forms and granules. In the near future, I will be posting a live Lyme movie showing the various forms of Lyme under the microscope changing into various forms and back again. Cystic forms are not degenerative bacterial fragments, since researchers have demonstrated protein synthesis requirements and it has been unequivocally proven that Lyme cystic forms are infectious.
- A cell wall-attacking IV cephalosporin may not have been the ideal antibiotic choice for the treatment of cell wall-deficient organisms in patients with late-stage Lyme disease. In this paper we see no sense of awareness of the over 20 ways Lyme evades the immune system and alters lab results.
- Ceftriaxone for Lyme disease has been documented as frequently not fully eradicating human Lyme infections. Why? Cephalosporins like Ceftriaxone do not achieve intracellular penetration.
- Lyme has been documented within a variety of cell types, including but not limited to endothelium, fibroblasts, lymphocytes, macrophages, keratinocytes and synovial cells. These findings are critically important since treating chronic infections requires attention to this type of Lyme hiding in the human body. This issue was utterly and completely ignored.
- I am currently finalizing a book on Babesia, one of many co-infections carried by deer ticks. One of the common causes of persistent Lyme disease is failure to treat a co-infection like Babesia, which is unlikely to be killed with either medication in this study and which can cause someone to feel quite ill.
In conclusion, any physician quoting this study as if it were the Ten Commandments is naive.
For references and more detail see: www.ilads.org/position2.html"
Phillips S, Bransfield R, Sherr V, Brand S, Smith H, Dickson K, and Stricker
R. Evaluation of Antibiotic Treatment in Patients with Persistent Symptoms of
Lyme Disease. An ILADS Position Paper; April, 2003
In contrast to the Klempner study, we find the Columbia researcher Brian Fallon et al (not yet published) who has presented his results repeatedly, e.g., October 22, 2004 at the Columbia University/Lyme Disease Association Conference in Rye, NY (Press release). In his study, in which only 1 in 100 met the profoundly strict unimpeachable criteria, patients were given ten weeks of intravenous ceftriaxone or placebo given to chronic Lyme patients with ongoing memory impairment.
Fallon's study had several blinds. This level of methodology has never before been attempted in a study of chronic Lyme disease. One of the reasons that many levels of blind were used in Fallon's study has to do with the controversy surrounding Lyme disease. The aim of this study was to include people for whom there was little disagreement in terms of a correct Lyme disease diagnosis. Secondly, the strict methodology, though tedious, was required because scientific rigor of a very high degree was necessary given the political nature of Lyme disease. In this study, patients with chronic Lyme disease were given SPECT scans before and after treatment. A SPECT scan of the brain measures blood flow activity within the brain. This is a physical marker that can scientifically examine cause and effect as opposed to questionnaires that are open to the opinions or capacities of the participant and influence of the examiner.
Patients were also administered purely objective quantitative examinations aimed at assessing disability, i.e.: neuropsychological testing. Lastly, as in other studies, patients were asked how they felt after treatment. All of these tests included several degrees of blind, i.e.: radiologist blind to diagnosis, neuropsychiatrists blind to diagnosis, patient blind to treatment, etc..
The patients had significant improvement in both physical and cognitive symptoms. Physical improvement was maintained at 12 weeks follow-up. However, patients relapsed on cognitive measures at follow-up, suggesting longer regimens may be required. Objective improvements in cognitive functioning correlated with changes in blood flow to the brain as measured by SPECT scan.
It is important to note that Fallon et al's study is the only biological examination of chronic Lyme disease to date. In the two other studies, results were interpreted using questionnaires, often administered over the phone.