Drug promises end to migraine misery

Heart treatment produces 'spectacular' results for chronic migraine sufferers

A British doctor is leading a drugs trial that could spell the end of the misery endured by thousands of migraine sufferers. John Chambers, a consultant cardiologist at Guy's Hospital London, says that when, on a mere hunch, he tested clopidogrel, a simple clot-busting drug, on five patients plagued by migraines, it worked, in some cases, "spectacularly well".

Now a wider trial on 280 patients is under way with the results expected next year. If the drug proves similarly effective, it could mean an end to the throbbing head, nausea and flashing lights that characterise a typical attack.

Migraines affect at least one in 10 people in the UK and attacks can last as long as three days. Sufferers often feel drained of energy for a couple of days after an attack and, on average, experience 13 attacks a year.

Currently, migraines are treated with beta blockers, to lower blood pressure and regulate the heart, as well as anti-depressants. Other treatments include aspirin, paracetamol and stronger pain killers, such as Migraleve, which contains paracetamol, codeine phosphate and buclizine hydrochloride.

Dr Chambers's treatment is based on the hypothesis that migraines can be caused by tiny blood clots that form in the heart and travel to the brain, disrupting the blood flow and causing the typical symptoms of one-sided headache, nausea and photophobia (sensitivity to light).

Clopidogrel is prescribed to heart patients to make their platelets less sticky. Platelets are, after the red and white blood cells, the main constituent in blood that helps to make it clot when a blood vessel is damaged. However, if the the platelets are too sticky, there is a risk of unnecessary clots forming in the blood vessels, breaking off and travelling to the lungs or the brain where they could trigger a potentially fatal stroke or embolism.

Dr Chambers believes platelets play a crucial role in the genesis of migraines in some patients. "No one quite knows what causes migraine. It is very common affecting maybe 10 per cent of the population and it can be debilitating and difficult to treat. To have another class of treatments would be very useful," said the cardiologist.

"Something in the platelets seems to be released that affects vascular activity. Where they stick to the artery wall, it may change the muscle tone, either constricting or dilating [the artery] and causing migraine.

"The first patient I tried the drug on had had almost daily migraines for 20 years. They had made his life a misery. I gave him the treatment and they melted away. It transformed his life," Dr Chambers said.

His discovery might have languished there, but a chance meeting Dr Chambers had which spurred him on to the track of a more novel potential treatment.

The larger trial came about after he treated Professor Sir Cyril Chantler, the chairman of Great Ormond Street Children's Hospital and the Kings Fund, the health policy think tank, and a senior figure in the NHS for more than 20 years, who is also a long-term migraine sufferer.

People who have heart surgery sometimes develop migraines after they have recovered from the operation, and Sir Cyril's migraines returned with a vengeance after he had an operation to replace a valve in his aorta (the main artery taking blood from the heart) two years ago. For 20 years they had been well controlled with a daily aspirin. Dr Chambers suspected the foreign material used to create his new aortic valve was the culprit, causing tiny clots to form and break off.

"Cyril was having a lot of trouble with migraine after the valve replacement," he said. "I knew he had done well on aspirin before and I thought it was worth trying clopidogrel. I had treated one other patient before him and it had worked spectacularly well."

Sir Cyril had recently helped establish a new research grant, called the Serendipity Award, for the Dunhill Medical Trust to back hunches just like the one Dr Chambers had. "He was cooking up the Serendipity awards at the time and he suggested I apply. So I did." The cardiologist was awarded 90,000 to test his treatment on a larger group of patients.

Dr Chambers's hypothesis is that patients who respond to clopidogrel may have an undiagnosed hole in the heart a condition known as "patent foramen ovale", in which a valve separating the two sides of the heart is not fully closed. This allows blood from the veins carrying tiny clots, which are being formed all the time, to leak across the heart into the arterial system, from where they may be carried to the brain.

The foramen ovale normally closes at birth, but in 20 per cent of people it remains potentially openable under pressure, as the heart pumps.

"We are looking for an association between foramen ovale and migraine. Closing the valve could cure the migraine. But the surgery carries a small risk and it may be possible to treat patients with the drug instead," Dr Chambers said.

"The hope is that we could save people from a potentially more invasive treatment."

Christina Chacksfield: 'My head throbs and I can't help yawning'

Christina Chacksfield, 45, an adult education administrator from Lingfield, Surrey, has suffered from migraines since she was 11.

"My migraines started when I was 11 or 12 years-old. I used to get them when I was at school and would try and carry on but I remember coming home feeling unwell.

"I can tell when a migraine is coming. I feel groggy and I can't focus on what people are saying. I can't see out one of my eyes, then the headache begins over the eye. It is very hard to describe what a migraine is to someone who has never had one.

"My head throbs and I yawn a lot. I can't stand bright lights or heavy smells and I feel nauseous.

"I have been under the care of various GPs since I was 11 and I have been on numerous prescription drugs during this time. I was on beta blockers and mild anti-depressants because they thought it might alleviate the pain.

"I was getting at least twelve or so migraines a month but I made a radical change to my lifestyle and now I only get about three a month. I eat a lot of wholegrain foods and avoid sugary or processed foods.

"I could never identify a precise trigger, but if I had a couple of late nights or if I'd had a few drinks the night before, these things would add up and then I would probably have a migraine.

"I still use a drug called Immigran but I was told I was taking too many, which was having an adverse effect. Basically I would take them when I felt a migraine coming on and then the next day it would come back.

"I also take high strength multi-vitamins with extra magnesium I find the migraines are worse when I am not taking the vitamins.

"Nowadays I try and stay at work because you don't want to be seen as one of those people who goes home all the time because they have a headache. I'm lucky because I have a part-time job which is quite flexible."

Cyril Chantler: 'It certainly worked for me the headaches disappeared'

"In the mid-1980s I began to get serious migraines. I was chief executive of Guy's and St Thomas'. This was classical migraine. I had read that platelets could be involved and so I thought why not try a daily low dose of aspirin? When you cut your finger the platelets activate and cause the blood to clot. That was my idea of what was causing the problem. I started taking one aspirin a day. It worked for me. I tried get someone to do a proper trial but didn't succeed. Two years ago I had an aortic valve replaced and started getting awful migraines. I spoke to John Chambers [consultant cardiologist at Guy's hospital] and he suggested it could be the material used for the valve causing the platelets to clump. He suggested clopid-ogrel. After three months I stopped and they came back. I took it for another three months and since then haven't needed it. I am a trustee of the Dunhill Medical Trust and we were thinking of establishing the Serendipity awards to back doctors who had hunches and needed funds. I mentioned my experience to a colleague on the trust and we agreed it was the sort of thing we wanted to support. The trustees agreed his proposal. He is the first holder of the award. It is difficult to get funding for this sort of research. We are keen to get others to apply but the closer to patients it gets, the more interested we are."

www.dunhillmedical.org.uk

Migraine attacks

* 1 in 10 people suffers from migraine attack, an average of 13 times a year

* Attacks last up to 72 hours

* An attack involves a throbbing headache with at least two other symptoms: nausea, raised sensitivity to light, sound or smell

* The pain is made worse by movement and sufferers want to rest and keep still in darkness

* Some sufferers have neurological disturbances, or auras, before the headache starts such as flashing lights, blind spots and zig-zag patterns but also including tingling, pins and needles and numbness

* Some people experience the auras only, or with only a mild headache

* Migraine is more common among women and is often linked to hormonal changes

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