Back from Denver National Jewish.....(Kalydeco trial)

[lifeisgood729]

Autumn,

Sorry you weren't able to get into the trial. The information from the trial coordinator about FDA label expansion is hopeful, though. Knowing how K has helped me and others with residual function mutations, it's encouraging to hear they must be seeing good results in the trial. I truly hope it comes soon for the thousands of people waiting.

Martha

 

[websterhome]

Elastase & Pancreatitis

Hey Everyone!

I know there were a few people interested, so I decided to start my own thread about my Denver experience.

Sooo.... I made it to Denver on Tuesday to be screened for the Kalydeco trial. For those who don't know, it is the trial for residual function mutations. In order to get in, one must meet at least one of 3 criteria: A sweat test under 80, pancreatic sufficient, or diagnosed at or after age 12. We know that I don't meet the second two, so I can only get in if my sweat test comes in at or under 80. It was 83 when I was diagnosed in 1981, so it's really questionable. However, they seemed optimistic that I would get in.

So my sweat test was an adventure in and of itself. After stimulating the sweat and waiting the 30 mins, I did not have enough sweat for the test! So the research coordinator told me she was going to have me run/walk a few laps in the hall to sweat more. I honestly thought she was kidding and laughed. Nope, she was serious as a heart attack. So off I went. Upon returning, I had sweat a little more, but still not enough. She collected that sweat, and then had to do a second test to try to get more. This time, she and the doctor had me go outside and make a lap around the hospital in the 90 degree heat. Still didn't sweat much, but in the end she thinks it is probably enough for them to test. If we went through all that only to find out it's not enough sweat to be tested I will crap! My feet are blistered and sore from jogging in sandals! Who would of known I needed tennis shoes and a sports bra for the screening!!! LOL.

The trial has already be underway for a while, in fact, some participants are already at or nearing the end. I'm not sure the reason, but they decided to open it up to a handful more participants. This trial is more involved than any trials I have done in the past. I do PFTs and pulse oximetry at home every morning and every night. The results are sent to Vertex through a smart phone supplied by them. I also wear a pedometer type thing 24 hours a day. Interesting stuff. So they've already got me started with those things, even though we don't yet know whether or not I am in.

Well, I guess that's about it! I will update you all as to whether or not I get in!

Take Care,

Autumn 32 w/CF

PS. A few points in case anyone is interested... my residual function mutation is S945L. Also, I have mentioned in the past that I am mostly pancreatic sufficient, so you may be wondering why I say that we know I don't get in on that criteria. Well, my fecal elastase number is very low, which does not reflect my need for few to no enzymes. They think that the low elastase numbers are a result of having pancreatitis many times. They said that for whatever reason they are seeing low numbers in people who have had pancreatitis. Interesting.

Hello! I was so interested in your comment re: elastase levels, kalydeco & pancreatitis. My daughter is 5, has g551d & n1303k and in December of 2012 had pancreatitis for the first and only time. Actigall (ursodiol) helped, no hospitalization, iv's or pain meds were needed. Her amylase & lipase came back to high normal levels right before starting kalydeco. She's been on kalydeco now for 6 months, her sweat test went from 87 to 18, her elastase went from less than 50 to 262 and her amylase & lipase are absolutely perfect now. There's a part of me thinking we may be able to go without enzymes but your comment about running a high elastase level due to a history of pancreatitis makes me curious.... Any idea what this connection is? I've had a hard time researching this aspect of PI/PS & CF, especially involving kalydeco. As best I can tell, elastase levels were not checked during clinical trials of kalydeco?

Thank you for any insight you might be able to provide!

Christy

 

[LittleLab4CF]

Christy,

Most of my CF issues are south of the diaphram, and my 63yr. old pancreas is still working and hurting like sin. The pancreas is capable of regeneration as long as it is a viable organ. Pancreatitis and cholestasis result from thickened pancreatic juices remaining in the pancreas and thickened bile respectively. Blockages in the ducts of both the pancreas and bile ducts can cause the disorders to become acute. Infections and long term inflamation begin to reduce the diameter of the ducts and this could become permanent over time. Kalydeco is thinning all these nasty digestive aids so they flow properly.

The easy answer is to start reducing the amount of enzymes currently being used. The numbers you describe don't signal total PI by any measure, in fact they sound pretty promising. Assuming your daughter has a formed stool currently, if the peanut butter poop signalling malabsorption starts up after a fair trial, you will be able to tell if she is digesting nutrients. Count on this being tricky, changes in medical protocol change bowel habits for a while, after an unknown period of time so put on your thinking cap for this. Creon is sort of a black art already so think of your daughter's GI tract like a giant water balloon. If you poke the balloon, it might take a relatively long time to see the the effect of that one perturbance.

By thinning bile and the digestive coctail that dumps into the duodenum, chances are very good, they will begin to flow when and where they were intended to go. Bile is a waste product of the liver that helps break down fats in the duodenum and beyond so the liver can't stop producing bile, hopefully the thinned bile will be delivered on time, a common problem with those of without gallbladders. Unless the pancreas is totally destroyed, it will produce enzymes and even at five, it could be. I don't believe it is beyond repair just based on the numbers she is showing in her elastase test. If she is producing adequate enzyme levels, which may improve when oral enzymes are reduced or hopefully suspended, this would be what I expect from a G551D mutation under the influence of Kalydeco.

There are a lot of half baked ideas floating around enzyme supliments. "If you start taking them, your pancreas will totally give up", is a favorite one of mine. If this actually worked, I might be tempted to send my very painful pancreas in to a fast death in hopes it stops barking at me with load of Creon. Printer alerted us of excessive enzymes on the large bowel so that may be an issue to include in the benefits of going without or with less enzyme requirement. The dirth of data on Kalydeco and digestion is beginning to sound like an old song.

Cystic Fibrosis was so named because of the fibrosing or cystic scarring of the pancreas in part because pulmonary issues were sudden death and not noticed in post mortem exams. Live CF patients showed malnourishment and again the digestive system was always suspect especially in times where good nutrition was fairly understood and available. Extending the lives of CFers overwhelmed by respiratory problems has been a primary focus for good reason and now with fair success. If CFers feel marginalized because their condition is invisible to the casual observer, GI dominat CFers and CRMSers are relegated to the narthex.


Now that respiratory/pulmonary dominant CFers have been given longer lives, they might die from constipation instead. The primary reason I am looking at Kalydeco or such as a CF moderator is from the few reports of people having improved pancreatic function on this site. As a researcher, I have subscriptions and the means to access more on CF than most are willing to pay for and the information is not out there.

For unknown reasons pancreatitis evades diagnosis when I have the gold standard abdominal CT, but direct measure of a pancreatic function test yields a clear, thick syrup that pegs the meter for bad. Kalydeco, doing its job yields substantially thinner, volumonous amounts of fluid to carry the enzymes and sodium bicarbonate through the pancreatic and common bile ducts . With your daughter's bile ducts purged of sludge, bile should be thinner, and life will get even better. Just from the simple effect of the mucosal cells no longer sucking up all the water, regardless where those cells are, the condition of any mucus gland and its fluid quality should almost be normal for your daughter. Let's hope.

LL

 

[triples15]

Autumn,

Sorry you weren't able to get into the trial. The information from the trial coordinator about FDA label expansion is hopeful, though. Knowing how K has helped me and others with residual function mutations, it's encouraging to hear they must be seeing good results in the trial. I truly hope it comes soon for the thousands of people waiting.

Martha

Thanks Martha. Yes, I agree, it is hopeful info. about the label expansion. I hope when/if it is expanded, however, that having a residual function gene is enough. I know CFTRsplicing mentioned that they may also look at phenotype when deciding who gets it. I'm guessing since I didn't get into the study based on the fact that my disease doesn't present as a residual function mutation (based on fecal elastase, sweat chloride, and age of diagnosis), I might not get Kalydeco if that was the case. Blah. So confusing.

I agree, I hope it comes out soon for EVERYONE!!


Thanks again and take care!!

Autumn 32 w/CF

 

[triples15]

Hello! I was so interested in your comment re: elastase levels, kalydeco & pancreatitis. My daughter is 5, has g551d & n1303k and in December of 2012 had pancreatitis for the first and only time. Actigall (ursodiol) helped, no hospitalization, iv's or pain meds were needed. Her amylase & lipase came back to high normal levels right before starting kalydeco. She's been on kalydeco now for 6 months, her sweat test went from 87 to 18, her elastase went from less than 50 to 262 and her amylase & lipase are absolutely perfect now. There's a part of me thinking we may be able to go without enzymes but your comment about running a high elastase level due to a history of pancreatitis makes me curious.... Any idea what this connection is? I've had a hard time researching this aspect of PI/PS & CF, especially involving kalydeco. As best I can tell, elastase levels were not checked during clinical trials of kalydeco?

Thank you for any insight you might be able to provide!

Christy

Hi Christy!

It's actually LOW elastase levels they are seeing in relation to pancreatitis. In order to qualify for the study under the fecal elastase criteria it needed to be 250 or over. My fecal elastase was 25 when tested a few years ago, and when tested last week for the study she told me it came back "virtually zero". So I don't know what the exact number was.

My number seemingly should be a lot higher because I take few to no enzymes. And by few to none I mean that I generally take none with snacks/small meals. If I am going to eat a huge fatty meal I will take 2-3 of the lowest strength Pancreaze. I had never had a problem keeping weight on (actually was borderline overweight), however, since my daughter was born almost 2 years ago I have had a problem with my weight due to breast feeding. Now that we are barely breastfeeding my weight is coming back up, so I don't think that will continue to be an issue.

So the point to my rambling is to say that even though it seems like I am mostly pancreatic sufficient, my fecal elastase is RIDICULOUSLY low. The study coordinator mentioned they have seen these super low numbers in other patients who have had pancreatitis, despite the fact that they require few (or no) enzymes. She didn't offer any hypothesis why that would be, I'm sorry. She did sound like they were at least somewhat surprised by the finding.

I'm not sure about the other Kalydeco trials, but for this particular study they are testing fecal elastase at screening, as well as at the final visit.

The fact that your daughter's numbers are that high after starting Kalydeco is awesome. And like I said, pancreatitis is actually causing LOWER elastase numbers, so your daughter's numbers are definitely not inflated due to it. I am with Littlelab. I think the best way to know about your daughter's pancreatic sufficiency is to try reducing her enzymes and see if there is an effect. If not, you can further decrease them and so on. I'd bring it up with her doctor first of course.

I have heard of many people on Kalydeco saying they no longer need enzymes, however, these are just personal statements and it seems like some are trying to refute that Kalydeco is helping with pancreatic function. However, I agree (once again) with Littlelab, for the reasons he outlined that it seems probable that Kalydeco is also helping with digestive issues.

I hope I somewhat answered your question! Let me know if I can help any more!

Thanks and good luck to you and your daughter! TAke care,

Autumn

 

[lcdbot27]

I'm actually part of this study, though I obviously must keep quiet about my results so far. Just wanted to say that I actually hit all three qualifiers (diagnosed at 20, sweat test at 35), the most surprising was that I was the normal range for pancreatic sufficiency (I believe my number was in the 500's). This was a shock to me as I've always been underweight and have been on enzymes since my diagnosis. I was diagnosed at 20 but never had GI issues that seem to be common in most people with CF, except for being underweight. I'm not going to mess with my enzymes until I'm done with the study and I can work with my doctor, but I'm also wondering if I can potentially lower my dosage without negative effects.

 

[LittleLab4CF]

Thank goodness other responses have provided some good information. My efforts to find out what is happening concerning trials for Kalyedeco and similar drugs had underwhelming results. I probably wasn't the first person that hour, let alone this year to pump the poor guy for the scoop on trials.

What I did glean was this. All the current trials are closed and no new trials are in the queue. Trials going on seem to be focused squarely on delta F508 mutation and they are "quite exciting", so draw your own conclusion on that one. My sense is the trials are having similar results to G551D. Kalydeco is pretty well past the need for more trials needed for FDA approval which he sees as good because it will make it more available for the wider range of mutations. I was hoping for more but the best news really is the genuine promise of treating most of the CF popultion. It looks like it will treat single and double copies of delta F508(del). The old figure of 66% of the CF population was based on homozygous or double copies which now has to be even more CFers by a lot. Sorry I didn't gather more. Right now it's "don'tcall us, we'll call you".

LL

 

[websterhome]

Thank you for your help!

LittleLab & Autumn,
Thank you both so much for your incredibly helpful responses! This is exactly what I was thinking, praying & hoping for -- I will be meeting soon with my daughter's CF GI doc and will discuss with him trialing one month off of enzymes. During that month, I will propose that we check her weight weekly and I plan on keeping a journal of any tummy aches, stooling patterns, appetite, etc. At this point, we have stopped giving her enzymes with snacks -- which is pretty huge to have no meds at pre-k! Hallelujah! 3 times per day she takes 4 creon 6000 and then of course 2 times per day she takes kalydeco. Tonight I found this http://magicbluepill.wordpress.com/info-for-people-on-kalydeco/ helpful in regards to specifics on fat intake with kalydeco doses, I will make a point of following this as best we can. In addition, she does hypertonic saline nebs morning and night with her vest & pulmozyme nightly after the vest. Do you recall the reason why I believe patients in the kalydeco trial didn't take hypertonic saline?

Thank you again! So very helpful!
Christy

 

[rmotion]

Christy,

Most of my CF issues are south of the diaphram, and my 63yr. old pancreas is still working and hurting like sin. The pancreas is capable of regeneration as long as it is a viable organ. Pancreatitis and cholestasis result from thickened pancreatic juices remaining in the pancreas and thickened bile respectively. Blockages in the ducts of both the pancreas and bile ducts can cause the disorders to become acute. Infections and long term inflamation begin to reduce the diameter of the ducts and this could become permanent over time. Kalydeco is thinning all these nasty digestive aids so they flow properly.

The easy answer is to start reducing the amount of enzymes currently being used. The numbers you describe don't signal total PI by any measure, in fact they sound pretty promising. Assuming your daughter has a formed stool currently, if the peanut butter poop signalling malabsorption starts up after a fair trial, you will be able to tell if she is digesting nutrients. Count on this being tricky, changes in medical protocol change bowel habits for a while, after an unknown period of time so put on your thinking cap for this. Creon is sort of a black art already so think of your daughter's GI tract like a giant water balloon. If you poke the balloon, it might take a relatively long time to see the the effect of that one perturbance.

By thinning bile and the digestive coctail that dumps into the duodenum, chances are very good, they will begin to flow when and where they were intended to go. Bile is a waste product of the liver that helps break down fats in the duodenum and beyond so the liver can't stop producing bile, hopefully the thinned bile will be delivered on time, a common problem with those of without gallbladders. Unless the pancreas is totally destroyed, it will produce enzymes and even at five, it could be. I don't believe it is beyond repair just based on the numbers she is showing in her elastase test. If she is producing adequate enzyme levels, which may improve when oral enzymes are reduced or hopefully suspended, this would be what I expect from a G551D mutation under the influence of Kalydeco.

There are a lot of half baked ideas floating around enzyme supliments. "If you start taking them, your pancreas will totally give up", is a favorite one of mine. If this actually worked, I might be tempted to send my very painful pancreas in to a fast death in hopes it stops barking at me with load of Creon. Printer alerted us of excessive enzymes on the large bowel so that may be an issue to include in the benefits of going without or with less enzyme requirement. The dirth of data on Kalydeco and digestion is beginning to sound like an old song.

Cystic Fibrosis was so named because of the fibrosing or cystic scarring of the pancreas in part because pulmonary issues were sudden death and not noticed in post mortem exams. Live CF patients showed malnourishment and again the digestive system was always suspect especially in times where good nutrition was fairly understood and available. Extending the lives of CFers overwhelmed by respiratory problems has been a primary focus for good reason and now with fair success. If CFers feel marginalized because their condition is invisible to the casual observer, GI dominat CFers and CRMSers are relegated to the narthex.


Now that respiratory/pulmonary dominant CFers have been given longer lives, they might die from constipation instead. The primary reason I am looking at Kalydeco or such as a CF moderator is from the few reports of people having improved pancreatic function on this site. As a researcher, I have subscriptions and the means to access more on CF than most are willing to pay for and the information is not out there.

For unknown reasons pancreatitis evades diagnosis when I have the gold standard abdominal CT, but direct measure of a pancreatic function test yields a clear, thick syrup that pegs the meter for bad. Kalydeco, doing its job yields substantially thinner, volumonous amounts of fluid to carry the enzymes and sodium bicarbonate through the pancreatic and common bile ducts . With your daughter's bile ducts purged of sludge, bile should be thinner, and life will get even better. Just from the simple effect of the mucosal cells no longer sucking up all the water, regardless where those cells are, the condition of any mucus gland and its fluid quality should almost be normal for your daughter. Let's hope.

LL

What is a good test to check for liver function, bile issues, enzyme function etc. Any ideas what is a good way to thin out the bile issue. What is the reference to peanut butter poop, the color or the float issue. Lighter color poop means a bile issue?
Thanks