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Posted: Wed Apr 05, 2006 10:55 am Post subject: Avonex plus Doxycycline trial preliminary results
An abstract from the AAN meeting about the combination trial of doxycycline and Avonex. The preliminary, small sample results look promising.
Combination Therapy with Intramuscular Interferon Beta-1a and Oral Doxycycline in Patients with Multiple Sclerosis: An Open-Label Trial
Alireza Minagar, J. Steven Alexander, Rhonda Brooks, Roger E. Kelley, Robert N. Schwendimann, Eduardo Gonzalez-Toledo, Dana Merrill Bryan, Shreveport, LA
OBJECTIVE: To determine the safety, tolerability, and efficacy of doxycycline combined with intramuscular (IM) interferon beta-1a (IFNb-1a) in multiple sclerosis (MS) patients experiencing breakthrough disease
BACKGROUND: Doxycycline is a potent matrix metalloproteinase (MMP) inhibitor that can potentially suppress destruction of the extracellular matrix and therefore limit the transendothelial migration of activated leukocytes in MS. Additionally, because MMP-9 is capable of cleaving IFNB potentially contributing to relapses during therapy, doxycycline may be expected to reduce the frequency of relapses
DESIGN/METHODS: This was an open-label, single-center, single-arm, cross-over study. Patients aged 18 to 55 years with relapsing MS, an EDSS score of 1.5 to 4.5, one or more gadolinium-enhancing (Gd+) lesions on MRI, continuous treatment with IM IFNb-1a for a minimum of 6 months, and a relapse within 60 days of their baseline visit (month 3) were eligible. Patients underwent MRIs at months -3, -2, -1, 0, +1, +2, +3. Daily oral doxycycline 100 mg combined with weekly IM IFNb-1a 30 mcg, began at month 0
RESULTS: To date, 15 patients have been enrolled and 11 have completed the study. The patients had a mean age of 42.013.3 years and 9 were female. An interim analysis included 11 patients with 1 pre-treatment and 1 on-treatment MRI and neurologic examination. During pretreatment (months 3, -2, -1, and 0), the mean number of Gd+ lesions was 10.36.6, decreasing to 6.25.4 during combination therapy (p=0.001). Mean pretreatment EDSS was 3.90.4 decreasing to 1.40.5 (p=0.001) during treatment. One patient had transiently elevated hepatic enzymes on combination therapy, none have withdrawn. Final results of MRI and clinical measures will be presented
CONCLUSIONS/RELEVANCE: Combination therapy with doxycycline 100 mg daily and IM IFNb-1a 30 mcg weekly appears to be safe and effective in patients with relapsing MS.
Joined: Nov 06, 2004 Posts: 365 Location: Ottawa, Ont. Canada
Posted: Wed Apr 05, 2006 3:31 pm Post subject:
So, obviously, some neurologists also think that adding antibiotics is a good idea. Would they have changed their minds or did I miss something?
Carole
Joined: Feb 02, 2004 Posts: 863 Location: California, USA
Posted: Wed Apr 05, 2006 6:39 pm Post subject:
great posting, dignan. A drop of 2.5 points in EDSS over 6 months is rather remarkable. _________________ Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.
A drop of 2.5 points in EDSS over 6 months is rather remarkable.
Remarkable yes Arron, but in a small (n=15) and open label trial (subjects expect to get better) is it statistically significant? As always isnt it the case that more research is required?? _________________ John
I am what I am
Joined: Feb 02, 2004 Posts: 863 Location: California, USA
Posted: Thu Apr 06, 2006 2:45 am Post subject:
indeed... _________________ Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.
The trial I'd be most interested in seeing is the doxycycline alone versus placebo. I'd love to see even a short term, open label trial on doxycycline alone to stir the pot. I post this gripe like a broken record, but gosh. I know pharmaceutical companies are not interested, but can't some foundation, some government that provides socialized medicine, some rich individual scrape up the money to run this study? How much would it really cost? There is the doctor oversight and all those MRIs, probably 70 or more. At least the tested drug won't be expensive. I wish I could just win a lottery and fund it myself.
Then an answer to any ethical criticism would be to run the antibiotic only (instead of interferon only) and the antibiotic + interferon. They could even do it as a blinded study (although it is hard to truly blind for interferon, due to side effects, etc.) There's already a lot of data on interferon-only, but not on antibiotic-only. If the antibiotic only is as good or even better than the interferon, that would be critical to know from a scientific standpoint. And we would all love to know the answer to that one for a treatment decision standpoint. There is a bunch of people out there who would jump to be on the antibiotic-only arm - I don't think recruitment would be a problem.
Joined: Feb 02, 2004 Posts: 863 Location: California, USA
Posted: Fri Apr 07, 2006 4:47 pm Post subject:
On a related note, the same can be said for the Minocycline + Copaxone trial, although in that case they did try minocycline by itself first (albeit in a very small trial)
http://www.thisisms.com/modules.php?name=News&file=article&sid=112 _________________ Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.
Joined: Oct 10, 2005 Posts: 409 Location: Missouri, USA
Posted: Sat Apr 08, 2006 7:54 am Post subject:
I'm surprised that Anecdote hasn't chimed in yet regarding the ABX. It does seem that ABX seems to be a treatment you can gain some EDSS points back on, even though a lot of what you hear is anecdotal. Could MS be of infectious cause?
Joined: Jun 18, 2004 Posts: 1472 Location: Bedfordshire UK
Posted: Sat Apr 08, 2006 8:26 am Post subject:
Well, I didn't chime in before because I have only just seen this. You have only to look in the Antibiotics and Regimens forums to know what I might have said. I never would have been prescribed one of the CRABs, even with doxycycline, so I had to go the full abx route. I'm glad I did. That's all.
Sarah _________________ An Itinerary in Light and Shadow
Completed Stratton/Wheldon antibiotic regime for aggressive secondary progressive MS in June 2007, after four years. Still slowly improving with no exacerbation since starting. EDSS was 7, now 2 or often less.
Joined: Feb 02, 2004 Posts: 863 Location: California, USA
Posted: Sat Apr 08, 2006 3:28 pm Post subject:
It, or at least some subset of the illness(es) collectively known today as "Multiple Sclerosis" certainly *could* have an infectious cause and/or trigger.
These studies are exceedingly interesting since they use cheap medicines that are readily available, however remember that tetracyclines (such as doxycycline and minocycline) have their own neuroprotective affects via their action on MMP, among other things. A nice, eloquent summary of that can be found here:
Discerning the effect of the anti-microbial versus the neuroprotective should be high on the agenda. _________________ Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.
Posted: Sat Apr 08, 2006 5:15 pm Post subject: Re: Avonex plus Doxycycline trial preliminary results
Arron wrote:
These studies are exceedingly interesting since they use cheap medicines that are readily available, however remember that tetracyclines (such as doxycycline and minocycline) have their own neuroprotective affects via their action on MMP, among other things.
That sounds like it might be similar to the function of lipoic acid as studied by the Oregon Health Sciences University.
Joined: Oct 10, 2005 Posts: 409 Location: Missouri, USA
Posted: Sat Apr 08, 2006 7:32 pm Post subject:
Arron, very good point. That is the 1,000,000 dollar/pound question at hand. Is it the neuroprotective or the anti-microbial action that is making the difference? I wonder if we might get a clue as to what the answer to this question is once Paratek releases the non-antibacterial tetracycline? If those who see beneift with ABX started taking this and still see the benefit, that would almost answer that question? Of course it would be much more complicated than that because you would have to do a double-blinded clinical trial on those who have and also those who haven't taken ABX.
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As always isnt it the case that more research is required?? 
