Minocycline trial results

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Minocycline trial results

Postby dignan » Mon Apr 30, 2007 7:42 am

Looks good, but comes with the usual proviso, "further investigation" required.



The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study.

Mult Scler. 2007 May;13(4):517-26. Epub 2007 Feb 9.
Zabad RK, Metz LM, Todoruk TR, Zhang Y, Mitchell JR, Yeung M, Patry DG,
Bell RB, Yong VW.
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.

Minocycline has immunomodulatory and neuroprotective activities in vitro and in an animal model of multiple sclerosis (MS). We have previously reported that minocycline decreased gadolinium-enhancing activity over six months in a small trial of patients with active relapsing-remitting MS (RRMS). Here we report the impact of oral minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in this cohort over 24 months of open-label minocycline treatment.

Despite a moderately high pretreatment annualized relapse rate (1.3/year pre-enrolment; 1.2/year during a three-month baseline period) prior to treatment, no relapses occurred between months 6 and 24. Also, despite very active MRI activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of the p40 subunit of interleukin (IL)-12, which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1. The activity of matrix metalloproteinase-9 was decreased by treatment.

Thus, clinical and MRI outcomes are supported by systemic immunological changes and call for further investigation of minocycline in MS.
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Minocycline

Postby Arturo » Mon Apr 30, 2007 8:49 am

It's great to hear it! In my opinion minocycline give us great promise for treat MS.

I have read results from other clinical trial with minocycline. Researchers show that minocycline reduce rate of new lesions by 84%. Minocycline was taken for 36 months 200mg twice a day.

I think that tetracycline related antibiotics like doxycycline or minocycline helps us becouse of its neuroprotective and antiinflamatory properities, but not of its bacteriostatic activity.

Sorry for my english :wink:
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Impressive Minocycline Trial

Postby Shayk » Mon Apr 30, 2007 7:14 pm

Arturo

Your English is just fine. Welcome to the site.

I agree with you that the results are impressive and minocycline has great promise for MS. From the abstract:
Despite a moderately high pretreatment annualized relapse rate (1.3/year pre-enrolment; 1.2/year during a three-month baseline period) prior to treatment, no relapses occurred between months 6 and 24.

The authors agree with your assessment that the effect is probably not due to the fact that minocycline is an antibiotic. From the article:
Because minocycline is effective in animal models of induced disease where the pathogen is not an infectious agent, it is unlikely that efficacy is due to its antibiotic activity, although this cannot be excluded as a contributing factor.

The fact that it has so many neuroprotective properties is definitely a positive IMO.

Also, last week I learned from the Accelerated Cure site that the journal, Multiple Sclerosis, which published the article, is allowing free access for a limited time. Hopefully the free access is still available. You can register here and the article is in the current issue.

Take care

Sharon
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Re: Minocycline

Postby CureOrBust » Sun May 06, 2007 6:40 am

Arturo wrote:I have read results from other clinical trial with minocycline. Researchers show that minocycline reduce rate of new lesions by 84%. Minocycline was taken for 36 months 200mg twice a day.
does anyone have a link to this study somewhere?
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Postby finn » Sun May 06, 2007 8:44 am

CureOrBust wrote:
Arturo wrote:I have read results from other clinical trial with minocycline. Researchers show that minocycline reduce rate of new lesions by 84%. Minocycline was taken for 36 months 200mg twice a day.
does anyone have a link to this study somewhere?

Actually, it's the same Canadian study done with ten MS-patients. The total lenght of the study was 36 months. Here are the results from months 0-6 (no abstract available), and here are months 6-24. Months 24-36 are not published yet.

-finn

btw, the dosage in the study was 2x100mg a day.
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley
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Minocycline

Postby Arturo » Sun May 06, 2007 10:03 am

CureOrBust wrote:
Arturo wrote:
I have read results from other clinical trial with minocycline. Researchers show that minocycline reduce rate of new lesions by 84%. Minocycline was taken for 36 months 200mg twice a day.
does anyone have a link to this study somewhere?


http://www.nationalmssociety.org/docs/H ... trials.pdf

Here is a list of clinical trials for last years. You will find this study here.
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Postby CureOrBust » Mon May 07, 2007 2:27 am

thanks all, but I have no problem finding references to studies involving MS and mino, its the dosages that I am having problems with. I was really interested after reading
Arturo wrote:Minocycline was taken for 36 months 200mg twice a day.
All dosages I have found have always been 100mg twice a day.
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Minocycline+Copaxone efffectiveness study.

Postby superman » Mon May 07, 2007 3:49 am

Hello,
I found this other article that still confirms the effectiveness of Minocycline when used with Copaxone.
I have the feeling that Minocycline has the same effect taken alone as with Copax., which lets me think that CRABS companies are trying to save their royalties by proving a random need of taking them+ some more efficient new drugs.
(this can be quite dangerous as seen with Tysabri+ Avonex :x )


Treatment With COPAXONE(R) Plus Minocycline Showed Substantial Reduction of Disease Activity in Patients With Active Relapsing-Remitting Multiple Sclerosis 05 May 2007

New data from a randomised, double-blind study showed that a combination of COPAXONE® (glatiramer acetate injection) along with the oral antibiotic minocycline reduced T1 Gadolinium (Gd)-enhancing lesions of the brain by 63 percent (p=0.08 ) in patients with active relapsing-remitting multiple sclerosis (RRMS), as measured by magnetic resonance imaging (MRI), compared to those receiving COPAXONE® alone. Additionally, the nine-month study demonstrated that treatment with COPAXONE® in combination with minocycline reduced the number of new T2 lesions in patients by 65 percent (p=0.06). These results trended toward but did not reach statistical significance.
These data were presented at the 59th Annual Meeting of the American Academy of Neurology (AAN) in Boston, MA, April 28 -- May 5, 2007.

"The results of this study indicated that further exploration of this combination is warranted, as the established effect of COPAXONE® on disease activity may be boosted when used in combination with minocycline for the treatment of active relapsing-remitting patients," said Luanne Metz, M.D., professor at the Department of Clinical Neuroscience of the University of Calgary, and principal investigator. "In these patients, the combination was safe and well tolerated," she added.

Minocycline is a broad-spectrum antibiotic, which is used to treat pneumonia, acne, and infections of the skin, genital and urinary systems, and the central nervous system. In a small proof-of-concept trial of 10 RRMS patients, minocycline demonstrated an 84 percent relative reduction in mean total Gd-enhancing lesions and was well tolerated, and data published in the Journal of Neuroimmunology indicated that the combination of minocycline and COPAXONE® decreased neuron-inflammation, axonal loss and demyelination in an animal model of MS.

"COPAXONE® is one of the most frequently used RRMS therapies due to its proven efficacy and safety and unique presumed mechanism of action," said Metz. "In previous studies, COPAXONE® has shown efficacy and safety both in combination with intravenous steroids and after induction with the immunosuppressant mitoxantrone; its compatibility with other compounds may make it unique among the disease modifying class of drugs and a treatment of interest for the future study of combination therapies for MS," Metz added.

About the Study

This double-blind, randomised study evaluated the safety, tolerability and efficacy of the combination of COPAXONE® plus oral minocycline in the treatment of RRMS patients with active disease.

Patients in this study (n=44) with one or more T1-enhancing lesions on their screening MRI were randomised to receive either COPAXONE® 20 mg daily plus minocycline 100 mg twice daily or COPAXONE® plus placebo for nine months. Patients were assessed clinically and by MRI scans at screening and months 1, 3, 8 and 9. The primary outcome was the total number of T1-enhancing lesions at months 8 and 9.

Forty patients completed the study. Groups were balanced at baseline except for greater T1-enhancing lesion number in the COPAXONE® plus minocycline group (median 3 versus 2; mean 7.62 versus 2.43 (p=0.07)). Despite this imbalance, treatment trended toward significance in the COPAXONE® plus minocycline group. At months 8 and 9, the number of T1-enhancing lesions was reduced by 63 percent (mean 1.47 versus 2.95; p=0.08 ) and the number of new T2 lesions was reduced by 65 percent (mean 1.84 versus 5.14; p=0.06), compared to COPAXONE® alone. Relapse risk rate was also non-significantly reduced in the COPAXONE® plus minocycline group (0.19 versus 0.41; p=NS).

Source: Red Orbit © 2002-2007 redOrbit.com. All rights reserved (05/05/07)
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Postby connieb » Mon May 07, 2007 3:37 pm

These results trended toward but did not reach statistical significance.
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Postby CureOrBust » Thu May 10, 2007 6:12 am

again, the study above used 200mg / day. Its the 400 (ie 200mg twice a day) i am finding hard to find.


On my search, I did stumble accross this document. It relates more to other neurological conditions, but may help explain how Mino works.

http://www.touchbriefings.com/pdf/1909/Bernado_Ref.pdf

It also contained this section:
In a second trial, 23 patients were given up to 400mg daily in an eight month cross-over trial (four months on the drug).The mean tolerated dose was 387mg daily. At higher doses, there was a trend toward more gastrointestinal (GI) adverse events and blood urea nitrogen and liver enzymes became elevated.
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Postby finn » Thu May 10, 2007 7:57 am

CureOrBust wrote:again, the study above used 200mg / day. Its the 400 (ie 200mg twice a day) i am finding hard to find.

I'd still say the study Arturo meant was the Canadian study, and the wrong dosage was just a misunderstanding or typo. At least the reduction in the lesion amount was the same in both cases (84%).

In any case, it seems to me that minocycline might work better alone than with Copaxone. Nine month treatment with Copaxone and minocycline reduced T1-lesions by 63% and T2-lesions by 65%. On the other hand, after six month treatment with minocycline alone none of the treated patients had any new MRI-activity (or relapses) at least for 18 months.

Be well.

-finn
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley
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Mino

Postby Arturo » Sat May 12, 2007 1:44 am

Sorry, I have made a mistake. Mino was taken 100mg twice a day.
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Postby tory2457 » Wed Jun 06, 2007 6:25 am

Hi all,

I have been diagnosed with MS since 1990.

I have been on Minocycline 100mgs twice daily along with "other" antibiotics since November 2006.

I am scheduled for new MRI's in July, and will post under Regimen my results and my protocol.

I'm very excited with how well I've been feeling, and can't wait to share my experiences.

the best,
tory
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Postby viper498 » Wed Jun 06, 2007 7:29 am

I can't wait to hear of your results either!
History:
Diagnosed 06/05; Nystagmus - Right Eye: MRI Numerous active lesions
MRI 07/06 - No active Lesions
Relapsed 03/07; Right leg, numbness
MRI 03/07 - A LOT more active lesions than the first MRI
Relapsed 05/07; Both Hands, numb; Torso, numb
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