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Journal of Neurological Science 2005 Jul 15;234(1-2):87-91

"Pilot study to examine the effect of antibiotic therapy on MRI outcomes in RRMSⁱ"

The rights to this paper are owned by Elsevier. the whole citation can be purchased
here

Abstract:

Sriram S, Yao SY, Stratton C, Moses H, Narayana PA, Wolinsky JS.

Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37212, USA. subramaniam.sriram@vanderbilt.edu

This trial examined the safety and possible MRI and clinical effects of anti-chlamydial antibiotic therapy in relapsing-remitting MS (RRMS). Newly diagnosed MS patients were selected to participate if they showed Chlamydia pneumoniae gene in their CSF and had one or more enhancing lesions on brain magnetic resonance imaging (MRI). After a 4-month run in phase of monthly MRI, patients were randomized to receive rifampin (300 mg twice daily) and azithromycin (500 mg every other day) for 6 months or placebo (PBO). Patients then had monthly MRI on therapy and two additional scans on months 12 and 14. Lumbar punctures were repeated between months 7 and 8 and within 2 weeks of termination of the study. Data on 4 patients on treatment and 4 on PBO were available for analysis. The primary outcome measure of showing a beneficial effect on enhancing lesions was not met. However, there was a significant difference in brain parenchymal fraction loss favoring those patient receiving antibiotics compared with PBO (p< or =0.02). Three of the four patients on antibiotic therapy cleared the organism from the CSF by month 12; in the PBO group one patient cleared the organism. The reduction in atrophy in patients receiving antibiotics must be viewed with caution, due to the small number of patients studied.

PMID: 15935383 [PubMed - in process]

Editorial comment: I have read the whole citation of this article. The tiny size with only 4 patients in each cohort means that it is not at all conclusive, though it makes some interesting observations about reaction to the treatment. Not clearly noted in the above abstract is the fact that the MRI used was very advanced and the difference in atrophy (parenchymal fraction loss)was significant between the abxⁱ group and the PBO with the abxⁱ group losing only .2 and the pbo losing 1.4% of volume. That is a huge difference in one year. The charts and graphs convincingly demonstrate these important differences, and the citation describes how these conclusions were arrived at. For interested persons the citation is a great resource. The fact that the primary endpoint was not met is not super important as this was a pilot study, and this unforseen but important benefit was uncovered. The size was too small and the time frame relatively short with treatment only going on for 6 months for anything to be certain, but that's the nature of pilot studies. In another study with more people it is possible the primary endpoint would be met, or that the parenchymal fraction loss would be different. It is interesting to note though that atrophy is an important feature of the negative side of MS and that it tends to accumulate with time. A therapy that alters the natural course of volume loss is significant.

Another point of interest is the difficulty they had recruiting for this trial. Just imagine you are approached with this offer: You get to participate in a trial after you have a lumbar puncture to see if you have CPn. If you have CPn, you will be given no treatment for 4 months during which MRI's will be done. For the following 6 months you will get either antibiotics or placebo, 50/50 chance. You will be followed for another 4 months after that , during all of which you will not be permitted any other medication or steroids. You will not even be allowed a steroid rescue if you have a big exacerbation. At the end you get another MRI and you have to have another lumbar puncture to see if you have cleared the CPn. Now I ask you, how excited would you be to participate in that trial?

In my opinion the MS society needs to get busy and approve the virtual placebo group. In this day when so many drugs are available it is unconsciounable to ask people to have no treatment just so placebo effects can be accounted for again and again in trial after trial. The only advantage to leaving it as is is that people are not sure if they are getting the active drug or not, though even this is dubious since the FDA requires every trial participant to be advised of all possible side effects of the active drug. In studies on just that, it has been shown that 80-90% of participants guess correctly whether they were getting the active drug or not in a supposedly blinded trial based on that information. So now I ask you how "blind" is a placebo controlled trial? Does it make sense to continue to ask people to go for a year with NO treatment for their MS in order to continue to pretend that these trials are superior since people are "blinded"? Nonsense.

Marie

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On CAPⁱⁱ since Sept '05 for MSⁱ, RAⁱⁱ, Asthmaⁱⁱ, sciatica. EDSSⁱⁱ at start 5.5.(early cane) Now 6 (cane full time) Originally on: Doxyⁱ 200, Azith 3x week, Tiniⁱ cont. over summer '07, Revamp of protocol in Summer '08 by Stratton due to functional loss; clarithromy