You are all aware of the Losartin paper by R. Cohn and colleague and like many other drugs/supplements/nutraceuticals, we continues to discuss this within the community and ask various physicians to prescribe Losartin for our boys. And some parents are giving it to their son, with or without the blessing of the physician. So, the botton line is that there is no evidence other than on study on the mdx mouse. And you have already heard the words, "there is a great deal of difference between the mdx mouse and the boys". And they are right. And from our side of things we ask "well, if there is potential gain with few (or no) side effects, why not?" and TIME matters. We want to EndDuchenne and as fast as possible.

So, where is the happy middle? I'm not sure we will find that tonight, but I did poll a few physicians (7) for some opinions and thought you might be interested in their responses. The responses fell into 3 broad categories.
1. One physician said - the recommended dose of Losartin is 25mg/day. The Marfan trial (and probably the dose range for a dmd trial) is 150-200mg/day. This dose is very high and increases the risk for toxicity. This physician did not thin 25mg or 50mg/day would have any effect.
2. Another physician said there is no evidence and they would not recommend it. When asked about a trial, this physician suggested trials cost millions of dollars and 'why spend money on a bandaid, when more meaningful trials are in development (referring to exon skipping. utrophin upregulation (summit, catalyst compounds), etc
3. Another physician repeated the words above and worried that patients would 'jump ship' if another, potentially more useful trial was announced. This physician also discussed the fact that most trials involve a minimum of 18 mo. to develop, recruit patients, analyze the data and report.
I thought you would like to know. I have some other ideas I'm exploring as well. Stay tuned.

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Comment by Pat Furlong on October 18, 2008 at 8:25pm
Re. Heart function. yes, this is a possible outcome for older boys, though here is the dilemma. Depending on the length of the trial, we may see no chhange. Steroids have impacted natural history and boys continue on steroids after loss of ambulation. Cardiac function remains fairly stable and so does FVC. FVC and cardiac measures are certainly outcome measures, but it would be good to have a more sensitive measure - such as fatigue (though very difficult to quantify), etc.
I agree about lifting a fork, quantity of fluid and combing hair. I am meeting with some groups on early Nov. and thankful for your suggestions.
Michelle I will ask about the monitor and swimming. it is an interesting idea.
Comment by Michelle Scaglione on October 18, 2008 at 4:49pm
Also since its waterproof he could wear it the pool and measure how long he can walk (or swim) around in the water before getting tired. I also feel that feeding himself also qualifies as something that affects his quality of life.
Comment by Michelle Scaglione on October 18, 2008 at 4:39pm
I will try to come up with something that could be measured for non-ambulatory boys. I few ideas I have I am not sure if it is what you are looking for. For example I have Johnny play whiffle ball in the pool,I check to see how hard he can hit it, he does switch arms so I can get an idea which is stronger. I ask him to raise his arms( I check the height, without compensating)I ask him to lift a glass(changing the amount of liquid each time) I ask him to comb his hair etc etc.
Comment by Paul Cliff on October 18, 2008 at 12:43pm
Aren't there already heart function measures that are routinely and regularly collected relatively frequently for non-ambulatory boys to catch heart dysfunction before it becomes lethal? It seems that we would want to collect this data as well.

Comment by Pat Furlong on October 18, 2008 at 8:01am
I forgot to add my thoughts on nonambulatory boys. We are all trying to think about oucome measures. One such measure that comes to mind is rolling over in bed. This is something that affects quality of life (sleep) and quality of the caregiver's life. Do you have other ideas? Let's think this through so we can develop some ideas about what makes a difference for our boys who no longer walk, that might be measured (quantified) in the short term of a trial -for instance if the trial was 12 mo.

Comment by Pat Furlong on October 18, 2008 at 7:56am
I am certain the experiment is being conducted in homes where parents either convinced their physicians to prescribe Losartin or found access in another way. There are plans for a 6 mo. multi-center trial in development but I am a bit concerned that 6 mo. may not be sufficient time to make a statistical difference. I have an idea in the back of my head (and maybe it should stay there...) but I am wondering if there would be any interest in this approach. Here goes:
You may have heard about the Step Activity Monitor (SAM). And I know this applies only to the boys who are ambulatory, but it might be something to start with. I'll say something about non ambulatory boys in a moment.
If we (would have to raise the $) bought a number of these SAMs (around 500) and had the boys wear them one week/month (for instance). They are water proof so would be worn all the time. We would have the boys wear them consistently for maybe 1 wk each month. We could establish a baseline for each boy, in other words, comparing him to himself rather than others. If we had a baseline and then you added a supplement or Losartin or whatever, we would simply continue to track steps at 1 wk/month over time. Keep in mind if the steps went up the next month, it would actually have no relevance, it would need to be determined over time... would the increase or decrease be constant, would it continue to go up or down? Over a period of months to years we would be able to determine the pattern. We (PPMD) would have the software and the SAM would need to be sent to us to download the info. each month. (if it is done through a clinic, would require a protocol, irb, etc. Since we are a nonprofit, we could collect data with your consent. We could NOT prescribe, rather only track changes over time. You would have to enter data about what supplement, drug, nutraceutical, therapy you added. It might be a way to begin to collect some interesting data. We would do it through DuchenneConnect and have biostatisticians evaluate the data. While it would not provide concrete evidence, it would show a trend (negative or positive) that would help us understand the benefit or not of a certain approach. If the trend is significant, we could move it into a clinical trial. I'm just thinking out loud. It's early saturday, maybe I need a few more diet cokes! :-)
Comment by Paul Cliff on October 17, 2008 at 7:08pm
That makes sense to me, but it would be nice to know whether it's 10% or something higher or lower, as well as whether the measurable benefit increases with the dosage so that we put up with some toxicity as we already do for steroids for some additional benefit. Again, it wouldn't shock me to discover that this experiment is being conducted informally in dozens of homes throughout our world, and I'd like to see the data. Time is not our friend here.
Comment by Michelle Scaglione on October 17, 2008 at 7:03pm
I believe the promblem with Losartan is that the DRS are saying you would need to prescribe 150/200mgs a day which would be toxic. Losartan is similar to enalapril. It works the same. The difference is Losartan may add the benefit of added muscle. But at 150/200mgs aday is too much. So people can put their sons on Losartan at the recommened dosage for the heart factor and if there is any other benefits that would be great. This is just my opinion. I feel that if each supplement or drug gives my son say 10% improvement if I added it all up maybe his total % for the day is 50% better than if I used nothing.
Comment by Paul Cliff on October 17, 2008 at 6:52pm
I'm just a simple, country lawyer so maybe I'm seeing things wrong, but I don't see why this is so difficult. It's not unlawful for a doctor to prescribe losartan "off label," and we all know that a number of doctors are doing so right now. What we need is for there to be some evidence to believe that Losartan is beneficial so that people are putting their already vulnerable children and finances at further risk. Data on the efficacy and safety, or lack thereof of Losartan is being generated already right now. The parents and doctors who are giving this drug to the boys should participate in a survey where the various clinical endpoints that have already been validated like the six minute walk test and the various cardiac function parameters are noted along with dosage schedules. Convince another group of parents, I for one volunteer my son (subject of course to his informed consent) to be in the control group. Check back at six months and twelve months, and if its making a real substantial difference it should be come apparent at that point, unless the methodology for all the other drugs that are currently being tested is completely wrong.

There are some logistics involved, but we have a large number of volunteers, myself and my family included to lick stamps and input data. I'm am sure that a number of the very fine doctors who have commited themselves toward the thankless task of keeping our boys alive who could analyze the data and present it in whatever format is necessary to get losartan added to the drug formulary that insurance companies, medicaid and medicare will cover. It's not beyond the realm of reason for one of the companies which manufacture what I understand to be generic drug to pony up some dough to cover the time and expenses of the professionals I am sure that I am oversimplifying this, but I'd like to know how.
Comment by Ofelia Marin on October 17, 2008 at 9:36am
"BY the way, FDA no longer categorizes dmd as terminal, rather a chronic disease. I understand it is ultimately lethal, but mean age of death is now >27 ."

I did not even want to comment on this...they can call it whatever they want, WE know exactly what it is.

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