Large Trial Of Oral Antibiotic Minocycline Set To Begin In People At Risk For MS
Exciting news of the launch of a Canada-wide clinical trial of the oral acne medicine minocycline to delay the development of MS was clouded by a published report suggesting the drug was harmful in patients with ALS, a nerve disease also known as Lou Gehrig's disease. Although ALS impacts a different part of the central nervous system than multiple sclerosis, the investigators who did that trial caution that their results may have implications for other neurological diseases including MS.
New Trial Begins:
The MS Society of Canada announced the launch of a mult-icenter clinical trial of the common acne pill minocycline to determine whether it can reduce neurological disease activity in people who have had a first attack of MS symptoms and are at risk for progressing to definite MS.
The trial is based on earlier studies suggesting the drug's anti-inflammatory properties may be beneficial, including a finding that minocycline could reduce MS disease activity, as detected by magnetic resonance imaging (MRI), by 84%. Minocycline is a relatively inexpensive pill available in generic form. In addition to its anti-inflammatory and antibiotic properties, the drug is thought to inhibit the death of nervous system cells by reducing the activity of specific enzymes.
Dr. Luanne Metz (University of Calgary) will lead the two-year, placebo-controlled trial to be conducted at 14 MS clinics across Canada. The dose proposed for the Canadian MS study, 200 mg daily, is half the highest dose used in the ALS study. According to a press release from the MS Society of Canada, enrollment will begin in early 2008.
Investigators Urge Caution:
Results of a large-scale, placebo-controlled clinical trial of minocycline involving 412 patients with ALS over 9 months of treatment found that neurological deterioration was faster in the minocycline group than the placebo group. ALS (amyotrophic lateral sclerosis) is a quickly progressive disease that kills motor neurons, the nerve cells of the central nervous system that send brain messages to muscles. Earlier smaller studies on minocycline in ALS had suggested it was safe.
The phase III trial, results of which were published in The Lancet Neurology (early online November 1, 2007), was conducted by Dr. Paul Gordon (Columbia University, New York) and colleagues with funding from the National Institutes of Health. In their paper, the authors caution that their results compel the need to re-examine the justification for other trials of minocycline in other neurological disorders.
Commentary: Dr. John Richert, Executive Vice President of the National MS Society (USA) Research and Clinical Programs, stated, "We applaud the MS Society of Canada for stepping forward to fund this important study. The idea that an inexpensive pill could be repurposed to treat MS is a very exciting prospect."
We have been informed that Dr. Metz and colleagues are aware of the ALS results. They believe that significant differences between ALS and MS, the lower dosage to be used, the ability to monitor MS disease worsening with MRI, and other factors will minimize risks to trial participants. However, they point out that there are risks of any untested treatment, and therefore caution against the off-label use of minocycline in MS or in suspected MS outside of the controlled setting of their clinical trial.
-- Research and Clinical Programs Department
Minocycline FAQ
October 2007
What is minocycline?
Minocycline is used to treat bacterial infections including acne; pneumonia and other respiratory tract infections; and infections of skin, genital, and urinary systems.
Minocycline is in a class of medications called tetracycline antibiotics. It works by preventing the growth and spread of bacteria. It comes in pill format.
Recent studies have demonstrated its anti-inflammatory properties, a key factor for MS researchers to look closely at the drug.
Are there any side effects?
Every drug has potential side effects. The side effects that are most common in people treated with minocycline include:
- diarrhea
- dizziness or lightheadedness
- grey discoloration of the skin or tissue in the mouth including the teeth
- sun sensitivity
- Secondary infection due to fungi which can cause itching of the rectum or vagina
How does it work?
Minocycline is believed to work by inhibiting the activities of an enzyme that is a key player in initiating inflammation in the brain in MS. It has been used in acne treatment for its anti-bacterial effects but studies have shown it also has anti-inflammatory properties, a key factor in slowing down MS.
Is minocycline a cure for MS?
No, but if the research hypotheses are confirmed, minocycline may prove to be an effective early treatment that delays the full onset of multiple sclerosis.
Early studies have shown an 84% reduction in MS lesion activity on brain MRI, meaning this treatment has the potential to slow the disease down significantly.
Will minocycline be a replacement for current disease modifying therapies?
Researchers note that minocycline wouldn’t necessarily replace current therapies, but would likely become another treatment option. Individual response is expected to vary. It may delay the timeframe in which other treatments would be required and it may prove to be useful in combination with other approved therapies.
How much does it cost?
In generic form minocycline can cost as little as $1 per dose. Based on two doses a day, this works out to approximately $800/year. Other MS disease modifying therapies can cost between $18,000 and $40,000/year.
Can I get it now?
Minocycline is generally available as a prescription medication for acne and other bacterial infections but until it is proven to be beneficial it is not recommended for treatment of MS.
Tell me more about the study: where are the goals and how is it designed?
Enrolment is expected to begin in early 2008. It is double-blind, placebo controlled and involves 200 people taking oral minocycline, 100 mg, twice daily. Up to 280 people will be screened for inclusion with the expectation that 30% will not be eligible.
Target population for inclusion: female and male, 18-50 years old, first MS symptoms within the previous 90 days and a brain MRI with at least two lesions present. This means that people who currently have MS or suspected MS will not be eligible for this clinical trial.
The goal of the study is to delay the conversion time from Clinically Isolate Syndrome (CIS, or the first attack of MS symptoms) to clinically definite MS. Clinically definite MS is based on a second relapse or very specific changes during follow-up on MRI.
The goal of the study is to achieve a reduction in the proportion of people who convert to clinically definite MS by the end of 6 months compared to placebo. The study will follow participants to the end of 24 months.
How can I get involved?
The best way to support MS research initiatives like this is by donating to the MS Society of Canada. Please visit www.mssociety.ca to donate.
For this particular study, enrollment does not begin until 2008. At this time, study sites will enroll people within 90 days of their first attack of MS like symptoms. People who currently have MS or suspected MS are not eligible.
What about the use of minocycline in other diseases like stroke and ALS?
Minocycline has been tested to treat other diseases like stroke and ALS with varied results. In MS, researchers are looking at minocycline to influence a target that is very specific to MS. Preliminary research has demonstrated that minocycline has great potential to slow down the progression of MS. This work has led to the development of a new $4 million phase III clinical trial involving 200 people and funded by the MS Society of Canada’s related MS Scientific Research Foundation.
What institutions and researchers are involved?
The clinical steering committee is comprised of:
Dr. Luanne Metz (principal investigator), University of Calgary, Hotchkiss Brain Institute
Dr. Anthony Traboulsee, University of British Columbia
Dr. David Li, University of British Columbia
Dr. Pierre Duquette, University of Montreal
Dr. Paul O’Connor, University of Toronto
Dr. Jack Antel, McGill University, Montreal Neurological Institute
Dr. Michael Hill, University of Calgary, Hotchkiss Brain Institute
Dr. Sam Wiebe, University of Calgary, Hotchkiss Brain Institute
Dr. Michael Eliasziw, University of Calgary, Hotchkiss Brain Institute
The biomedical research team is comprised of:
Dr. V Wee Yong (team leader), University of Calgary, Hotchkiss Brain Institute
Dr. Alexandre Prat, University of Montreal
Dr. Amit Bar-Or, McGill University, Montreal Neurological Institute
The independent safety monitoring committee is comprised of:
Dr. T Jock Murray (chair), Dalhousie University
Dr. Ruth Ann Marrie, University of Manitoba
Dr. Brenda Banwell, University of Toronto
In addition, the following institutions are involved:
University of Calgary, Hotchkiss Brain Institute, Calgary
Dr. Michael Yeung (Site Lead Investigator)
University of British Columbia, Vancouver
Dr. Anthony Traboulsee (Site Lead Investigator)
Fraser Health MS Clinic, Burnaby Hospital
Dr. Galina Vorobeychik (Site Lead Investigator)
University of Alberta, Edmonton
Dr. Gregg Blevins (Site Lead Investigator)
David Thompson Health Region, Red Deer
Dr. Jacqueline Bakker (Site Lead Investigator)
University of Saskatchewan, Saskatoon
Dr. Carol Boyle (Site Lead Investigator)
University of Western Ontario, London
Dr. Marcelo Kremenchutzky (Site Lead Investigator)
University of Toronto
Dr. Paul O’Connor (Site Lead Investigator)
Queen’s University, Kingston
Dr. Don Brunet (Site Lead Investigator)
University of Ottawa
Dr. Mark Freedman (Site Lead Investigator)
University of Montreal
Dr. Pierre Duquette (Site Lead Investigator)
Université Laval, Quebec City
Dr. Manon Thibault (Site Lead Investigator)
Neuro Rive-Sud, Université de Sherbrooke
Dr. Francois Grand’Maison (Site Lead Investigator)
Dalhousie University, Halifax
Dr. Virender Bhan (Site Lead Investigator)