We survived dosing appointment #2

It was a very rough day, but we're on our way home right now, with 2 heavily medicated kids passed out in the back, and 2 emotionally and physically drained parents in the front. Ari had mild reactions, and Aviv had significant reactions; both are doing alright now, and all any of us want to do is curl up in bed together and sleep.

We’re in!

We're in!

Two nights ago, I was a wreck, comfort eating (schnitzel, cake, you name it) to try to assuage my anxiety about the big screening appointment at Stanford we had the next morning.  We were told that the appointment, where the boys would undergo blood tests, scratch (skin prick) tests, physicals and finally blind food challenges, was going to be difficult, long, and critical in Dr. Nadeau’s determination of whether they would be included in one of her coveted and cutting edge desensitization studies. No pressure. It’s 48 hours later, and I am still recovering from the exhausting and amazing (in that order) day we had yesterday.  (If you don’t want to read all the details, feel free to jump to the end of this post - or the title of it - for the bottom line.)

We were on the road to Stanford yesterday, weighted down with bags of toys, books and an iPad filled with movies (we would have a lot of time to kill there), extra clothes (in case there was vomiting), food, and lots of jitters, before the clock turned 7am. Once at the hospital, Ari and Aviv were in the hands of a lovely team of medical professionals who work with Dr. Nadeau, who gave them physicals, drew blood, and administered skin tests to get some baseline information. Ari was quite calm during the tests, but Aviv was agitated (and he has a heck of a set of lungs on him, when he starts yelling); a role reversal from their usual reaction to blood/skin tests that started things out with some excitement. Based on those test results and ranking likelihood of exposure to certain nuts, we decided on a ‘top 3’ list of nuts for each kid that would likely be the three that they would be desensitized to in the study. But before that could occur, those 3 nuts – plus a placebo – would be given to the boys as part of a double blind challenge to confirm the allergy. What that means is that, on each of four ‘dosing’ days (yesterday being the first one), each kid would be given microscopic amounts of one of the nuts, increasing dosage throughout the day, to confirm  that the child is (1) allergic to the nut, and (2) at what dosage (i.e. what is the baseline from which to begin desensitizing). Double blind means that we wouldn’t know which nut they’re getting (or if they’re getting the placebo instead), and neither would the Dr. or her staff; the only person who would know is the nutritionist who mixes the pure nut flour into little cups of chocolate pudding or apple sauce for the kids to eat. 

So around 11:30am, with our kids hooked up to oxygen and blood pressure monitors, watching Star Wars for the first time (big day for them on many levels!), the dosing began. This was the part we were dreading. Blood and skin tests aren’t fun, but our kids have done them dozens of times and we knew what to expect; intentionally giving our kids the allergens that are so dangerous to them was a first, and I was terrified inside (while presenting as calm externally). First they were given .1mg of the allergen, and I watched like a hawk for any change in their demeanor or vitals. Every 15 minutes, the staff asked them a series of questions (do they feel itchy in their eyes/throat/anywhere, how is their breathing, do they feel they need to vomit, etc.) and checked their vitals. After observing no reaction for designated periods of time (15 minutes after the first dose, 30 minutes after the second dose, up to one hour intervals between dosings), the kids were given their next dose (1.6mg). Just to put the volume in perspective, a typical square of chocolate is 10,000mg. No reaction from either kid at the 1.6 dose, or the next one (6mg). At the 25mg dose, however, as soon as Aviv got the bite of pudding into his mouth, he began to freak out. His demeanor immediately changed, he became red and welt-y, and he began crying and yelling that his mouth “felt spicy” (which was his interpretation of the tingly/stinging feeling of his mouth reacting and starting to close up). To go back to the chocolate analogy, if you took a typical square and divided it into 400 pieces, one of those 400 pieces is what 25mg looks like. That’s the miniscule amount that caused Aviv to start reacting. The medical team was great – staying calm and medicating him immediately, but his welting continued to get worse for the next hour. A second dose of medication and topical cream helped to stop the welting, and he was done with dosing for the day. The challenge/dosing protocol says that the child continues escalating the dosage until the first of either 100mg is reached, or a reaction occurs; the child then needs to stay put there for two hours of observation after the final dose. (Interesting fact we learned: 74% of reactions occur within 20 minutes of ingestion, but another 22% take longer to react and can occur up to 2 hours after ingestion.) Ari, however, had no reactions during the day, and continued on until the final 100mg dose (and the 2 hours of observation after, which made for a VERY long day there). Having no reaction could mean that Ari received the placebo yesterday, or that he has a very low reaction trigger to one of his nuts, such that 100mg wouldn’t trigger it. (We think it’s more likely that it was the placebo, but we’ll know for sure at the end of the 4^th dosing appointment.)

While Aviv’s reaction was scary to watch, there was a great lesson in it for us. We got to see exactly how he reacts when he ingests nuts (not sure yet which nut), which is very helpful when educating others on what to look for with Aviv, as every kid reacts differently. We know how he reacted 2.5 years ago, but he hasn’t had an ingestion reaction since then (thankfully!), and it was an important learning.

Dr. Nadeau finally arrived as we were wrapping up around 4:30pm. It was interesting to see Aviv’s connection with her. They had bonded at the pre-screening appointment a few months ago, and he asked for her specifically all day yesterday. When she arrived at the end of our day, although he was zombie-like from the draining experience and the medication, he still wanted to hug her and spend time with her. She was amazing with both kids, before turning to us to talk. She told us more about the different trials she has opening up in the next few months, including that the one we want – the common auto-immunotherapy/desensitization protocol with the ‘accelerator’ drug, Xolair – has received FDA approval, and is now pending before the Stanford Internal Review Board (IRB); they expect to receive IRB approval within 3 weeks, and then move forward with opening the trial. We shared with her about our day, and how Aviv articulated what was happening with his body during the reaction, and she was very pleased as that’s a big deal from a 4 year old. She reviewed all of their test results, heard from us about the research we’ve been doing to feel comfortable with the Xolair study (many discussions with experts and reviewing data), and then told us that she had planned to have 15 kids in the Xolair study, but based on what she saw, she could add us to the study as numbers 16 and 17. I almost fell over. It seemed so surreal that I had to ask her for confirmation that she was saying Ari and Aviv would be included in the study. She was. She even drew me a picture of the time line of the study, gave us numbers of who to talk to for various needs, etc. I asked about how to handle the other nuts that Aviv is allergic to (that couldn’t be included in the 3-nut limit of the trial), and she assured us that she would work with us to figure it out, whether through periodic testing to see if we’re benefiting from a ‘bystander affect’ (where other nut allergies that aren’t being treated for directly essentially get treated by association) or by treating the other nuts ‘off protocol’. I don’t even know exactly what that means, but she made clear that she wouldn’t let us go through this whole journey only to still have nut allergies to worry about. (With one caveat – one of the nuts Aviv is allergic to can’t, at this time, be treated for, as the FDA hasn’t approved a source of the pure nut flour for it.) 

Assuming the IRB approves the study, it will begin in December 2011 or January 2012. Ari and Aviv can enter it once they’ve finished their dosing appointments (one yesterday; 2 scheduled for November; 1 more to follow), and then will begin 15 weeks of receiving a Xolair injection (once every 2 weeks). They won’t begin taking the allergens (in carefully measured/monitored daily doses) until week 9, and will ‘up-dose’ the amounts through week 24. After that, they’ll go through another 4 days of double blind challenges to validate that it worked. And then we all sigh. Or cry. Or both.

As we headed home, our bodies exhausted and our heads swimming with information, excitement and hope (and in Aviv’s case, antihistamines), we tried to make sense of it all. We all slept a lot more soundly last night than the night before, that’s for sure. In a testament to the hopefulness of children, while I’m still having trouble believing all that Dr. Nadeau said (even as I type this), Ari announced this morning, as he boarded his school bus to Kindergarten, that ‘he went to Stanford and they’re going to do treatment, so that by the time he starts First grade next year, he won’t have nut allergies anymore.’ As the saying goes: from his mouth, to G-d’s ears.

We’ve been scheduled for a clinical trial screening!

Just a quick note to share the amazing news that we've been scheduled for a formal screening appointment for the nut desensitization clinical trials at Stanford! We'll go on October 25th for a day (7ish hours!) of screening and food challenges. We're both excited and terrified.

I'll post with more info about what we've learned, etc. soon, but wanted to share the good news now.

Details on the 3 open studies

OK – I’m back, with sleep having done wonders. When I woke, Orr was already hard at work on the iPad, researching new info we learned yesterday, and the discussion – and awe – continued. [Note: there is A LOT of information that follows. If it’s too much, and you just want to know the bottom line, feel free to scroll to the bottom of this post.]

Yesterday, Dr. Nadeau pre-screened us, ran scratch tests on the boys to get a clear picture of the number/type of allergies we would all be working with, and answered our many, many questions with patience and grace, despite the fact that her offices were being packed up around her, as they are being moved into Stanford hospital space this weekend (from clinic space outside of the hospital). We had some funny moments. Aviv, early on, was sizing her up, then said to Dr. Nadeau, in his unmistakably Avivi voice, “Um, can I tell you something? I like blood tests better than scratch tests, so can I have a blood test instead?” Dr. Nadeau, understandably surprised to hear these kind of preferences from a 4 year old, looked at us. Heck – these kids have been having blood and scratch tests for years; they’re pros. Dr. Nadeau assured the boys that she would do the scratch test herself, and that it would be much less painful than a blood test. There had been a global-scale freak out at our house yesterday morning when A&A realized they would be having a scratch test – screaming “Noooooo! I HATE scratch tests!” with all accompanying waterworks. To be fair, the scratch tests they’ve previously had were done by their pediatric allergist who (as I’ve already alluded to) is, well, sort of the only game in town for pediatric allergists in Marin or SF. We’ve never loved his bedside manner, and feel he takes a less-than-cutting-edge approach, but we never thought twice about his equipment. Well… after seeing the so-easy-you-hardly-notice-it’s-happening equipment Dr. Nadeau used, Orr dubbed the former scratch test equipment that had been used on our kids ‘Inquisition-level torture devices. A&A hardly even broke their attention from the movie they were watching (yes – we brought an iPad with movies and headphones for them to watch, to keep them engaged while we talked with the doctor, reminding us, yet again, never to underestimate the power of the iPad) while she did the pricks. Aviv continued to test Dr. Nadeau – telling her exactly where he wanted the prick points (“no – not here… HERE”, pointing 2mm away) – and was very satisfied. She also used diluted amounts so that she saw the reactions she needed to see without sending them into full-blown itching/scratching/discomfort… another first for us with a scratch test. Bottom line on the tests: Ari appeared to be less sensitive to one of his nut allergies then when previously tested (woo hoo!), and Aviv is still holding strong at being highly allergic to many nuts.

The scratch tests confirmed their various allergies, and apparently we passed the are-they-a-normal-family-who-will-follow-directions-and-not-make-my-study-hellish test, which means we passed the pre-screening! That’s huge. She then told us about the three studies she has open, that are scheduled to begin in October 2011:

1) The first one (a peanut patch, which works like a nicotine or birth control patch, releasing tiny amounts of peanut protein to desensitize the body) is not a good fit for us, as the boys have allergies beyond peanuts. The second and third, however, sound amazing.

2) The second one (“the generic study”, as Dr. Nadeau refers to it) is the standard desensitization protocol that Duke made famous, and that she has been doing for years now: straight oral immunotherapy, which involves giving minute amounts of the allergen to the patient each day, with an escalation dose (i.e. upping the dosage of allergen) every 2 weeks, in order to slowly desensitize the body to the allergen. This study lasts approximately one year, and begins with a very rough week of tests and giving the allergen to the patient in increasing doses to determine the starting threshold level (that is, the highest dosage possible without sending them into anaphylaxis); that is apparently NOT a fun week. Following that week, the protocol officially kicks in: the patient is given pre-measured doses of the allergen at home daily, and then returns to the doctor for escalation doses every two weeks. Over time (usually about a year), the dosage is slowly increased from micrograms to actual serving sizes. By the end, the patient can have – and actually, MUST have – several (4-7) of each allergen nut each day. It’s imperative that the patient continue to ingest the allergen at the ending level every day in order to maintain the desensitization. Once the patient graduates from the study, he is considered in ‘maintenance mode’; there is no indication at this point as to what the future holds (whether there will be a time where they don’t need to eat that amount daily, etc.), so the current guidance is to continue having it indefinitely.

The twist here (from the standard oral immunotherapy studies that we’ve been following) is 2 fold: first, she will be treating 3 allergens at the same time. This means that, instead of Aviv going through the first year treating for peanuts, then beginning a second year of treating for hazelnuts, then a third year of treating for pistachios, etc., he can be treated for 3 nuts at one time – a HUGE time savings toward getting him to a safe place! Aviv has a laundry list of nuts he’s allergic to, so this is key for us. We also learned that some nut proteins are so similar that treating one may give you the cross-benefit affect of treating a second one; in other words, we might get a ‘freebie’ or bonus nut treated by treating certain other ones, so we’ll keep that in mind as we think about which ones to do first. The second twist in Dr. Nadeau’s study is that she has found clean sources for all of the tree nuts! Most of the studies/treatment clinics we researched do not treat for tree nuts because of difficulty in sourcing clean/uncontaminated tree nuts. In fact, the Dallas clinic we spoke to, that does straight treatment (not studies), said that they want to treat tree nuts but haven’t been able to due to sourcing challenges. Dr. Nadeau hit the same wall a few years ago and hired people to reach out to growers (we have the benefit of being in California, where so many of the nuts are grown) to get nuts directly, and received FDA approval to do her own testing for purity (as she’s a biochemist). So, she can treat for all the nuts we need. 3 at a time. Locally. Patients who are our boys’ age. Any one of those facts is amazing and a breakthrough; that all four are present is just a gift that I am so grateful for.

Downsides: the treatment is very, very hard on the patient physically and emotionally. 80% of kids in these studies have physical reactions along the way, usually abdominal pain and/or hives. A few have had more severe reactions (diarrhea, vomiting), but Dr. Nadeau told us no one in her studies have had anaphylaxis from the treatment. They are equipped to handle any of these reactions that occur in their offices, and we will be instructed how to handle them at home, with 24/7 access to the staff for guidance. Some kids even develop new stomach related physical ailments (Eosinophilic Esophigitis) along the way. Additionally, it is emotionally draining for everyone. We have all lived with the framework that nuts can kill our kids, and now we need to give them small doses daily. They can also have a very tough time in understanding what is going on, and why they have to ingest something that makes them feel bad. Finally, as their bodies are struggling to adapt, they are actually MORE sensitive/prone to reactions to errant nut exposure until the study is complete and they enter maintenance mode. It will be a time of heightened diligence and anxiety for all of us. With the number of allergies our kids have, it would likely be one year of treatment for Ari, and two years for Aviv, under this 3-at-once study.

3) The third study (I refer to it as ‘the accelerator study’) is where our eyebrows visibly raised. The third study takes “the generic study”, and accelerates the treatment time through the addition of a drug (Xolair). Initial research by Dr. Nadeau has shown that, when using Xolair on top of the standard oral immunotherapy protocol, the treatment is generally finished in 16 weeks. I’ll say that again: 16 weeks from start to finish; from life-is-dangerous to not having nut allergies. In fact, she believes that at around 9 weeks with the Xolair, the cross-contamination risk (from touching nut oils, etc.) is already gone. Those of you who have seen us wipe down every toy, seat, bench, in our vicinity can imagine what a life change that would be for us. Xolair works to decrease allergic reactions by boosting the T-cell production, and suppressing the IgE antibodies, which reduces side effects/reactions to the allergen and enables the ‘up-dosing’ to occur faster. Using Xolair in this way is already being done by a few research hospitals, including Johns Hopkins, Sinai, and Boston.

Using Xolair is not without its risk and downsides, as you can imagine. Xolair is currently only FDA approved for treating severe asthma in patients over 12 years old (it is approved for kids under 12 outside of the US). It has been known to cause anaphylaxis in some patients, which is why it must be administered in a doctor’s office. There is also some controversy as to whether it is connected to causing cancer, but Dr. Nadeau (and Johns Hopkins) does not believe that to be the case. (See http://www.hopkinsmedicine.org/bin/s/o/Xolairptinfoversion2C.pdf, for more info on Xolair risks.) In this accelerator study, Xolair would be administered by injection into the patient’s fatty tissue every two weeks for the first 9 weeks, then 1-2 times after that until the treatment is finished (I think 6-7 times total). It also doesn’t accelerate treatment in the same way for each patient, meaning that it may enable the treatment to end in 16 weeks, or it might take longer; it will vary by patient. In addition to the possible risks of taking Xolair, and the discomfort of the bi-weekly injection, it is an extremely expensive drug - $4000/shot; $20,000-$30,000 for the course of treatment. For that reason, Stanford is asking that anyone in that study contribute $10,000 (per study) to help diffuse the cost of the medication. (It’s illegal to charge for participation in a clinical trial, so this is not for participation; it’s directly toward the cost of the medication used, if one chooses to be in this study.) This would mean $20K-$30K for us, if we end up being approved for this study, and want to have all of A&A’s allergens treated in an accelerated manner. Just another factor to consider.

BOTTOM LINE: So where we’re at is waiting for Dr. Nadeau’s studies to be approved by the IRB (there’s no indication that they wouldn’t be, as they’ve already been approved by the FDA), so that we can be scheduled to come in for a formal screening/intake. The formal intake is planned to occur in September 2011, with the studies beginning in October 2011. So barring unexpected interventions (and assuming they are accepted into one of the studies), A&A will could begin treatment in nut desensitization studies in October at Stanford; the question is whether to request the ‘accelerated’ study or not. Either way, by summer 2012, assuming the kids are accepted into one of the studies, we could have kids with fewer-to-no food allergies. Hard to believe.

Note: if there’s anyone who wants detailed info regarding the work that is being done in this field, contact me (tinok94941@yahoo.com); I’ve been writing up what I learn along the way, and would be happy to share; I just don’t want to bore everyone here with research info.

The hour and 15 minutes that changed our lives

I’m so tired from processing information and emotion, that I really just want to go to sleep. I know some of you are waiting to hear how today went, though, and I don’t want to keep you waiting, so just a short update:  

It was an amazing appointment. Dr. Nadeau is an amazing person. Her intelligence, compassion, dedication to advancement in the area of food allergies was all palpable. When we got home today, I asked the kids what they thought of Dr. Nadeau. Aviv, without missing a beat, said, “She’s one of the best doctors I’ve ever had!” Ari jumped right in with, “She IS the best doctor!” Clearly, she made as big a fans out of A&A as she did out of Orr and me. So what did she say and do, and more importantly, what does our future look like? To cut to the chase: she will be conducting 3 food allergy studies (including two that can desensitize for tree nuts!) starting in October (pending approval from Stanford’s internal review board, or IRB) that A&A are eligible for, and – while there are definitely no guarantees at this point – it sounded very promising that they could be included in any of those studies. That news – that A&A could be in desensitization studies for all of their food allergies, close to home, with an amazing practitioner, as soon as October - is so amazing, I’m having trouble believing it, even as I type it.

I’m really too exhausted (from the anxiety before the appointment, then the surreal optimism/processing after it) to detail the studies right now, but will in the next few days.

Thank you for your calls and emails of support. If we move forward with this, we’ll need lots more! It takes a village…

Results!!

I wondered last night whether my appeal to Heather's heart strings would help, and apparently it did (or at least didn't hurt!)... instead of waiting months and months for an appointment with Dr. Nadeau, we heard from Heather today that Dr. Nadeau agreed to squeeze us in this Friday!! This is amazing, and I'm in a fog; it feels surreal. I'm both exited and nervous, and have no idea what (if anything) to tell the kids about the appointment. They're smart and good listeners, so they'll hear us asking questions. As big and hard to grasp as the idea of treatment was for Orr and I, I can only imagine how confusing (and emotional) it might be for the boys, so we need to think carefully about what to say to them. The mom I spoke with last week (whose son did the treatment a few years ago) told me that she didn't tell him that he was ingesting nuts during the study; she just told him it was medicine to help him fight his allergy, as it's hard for kids to make sense of why they MUST eat nuts in the treatment dosage, but need to keep up their standard nut-free restrictions outside of that (until the whole treatment course is finished).

We know very little right now about the studies that Dr. Nadeau has right now; we'll find out everything on Friday. We know that it's a study/trial, and not straight treatment (as the Dallas, Portland and Tel Aviv clinics are). What that means is that she must follow a strict protocol, and that some participants will be given placebos, I'm imagining. But it's here - local - which means we wouldn't have to move or fly weekly, and it has the backing and credentials of Stanford. I'm trying not to let myself get too excited yet, as the crash-and-burn feeling (if it's not the right fit for the boys), from having such an important hope crushed, can feel so devastating. Please think good thoughts for us on Friday.

Results or TRO?

Results or TRO? Only time will tell...  I just sent an email that runs the risk of alienating someone very important - Heather, the study assistant (aka gatekeeper) to the Stanford food allergy study with Dr. Nadeau. She could find it hokey or annoying, or it could endear her to us, and make us feel real and personal... like people she wants to help find a space for. Hopefully the latter...

I had emailed her to get an appointment last Friday, and heard back tonight. She seems very pleasant, but told me that a screening visit is the first step to being considered for the research study, and that there aren't any available for several months. I don't want to wait several months. It's like the scene from When Harry met Sally, when Billy Crystal says that when you realize who you want to spend the rest of your life with, you want it to start right now. Now that I know that (1) there is a treatment protocol which is proving to be successful, and (2) there is a research study happening now at Stanford, with space available... I want it to start right now. I want to start my kids on the journey that will take a long time and be tough now, because at the other end of that journey is a safer, happier life. What mother doesn't want that for her kids?

So yes, I sent Heather an email with the story I blogged about yesterday - about Ari saying for his 5th birthday that what he wished for, was to not have his nut allergy, and that as a mom, I just want to see them both safe. Hopefully she won't find it too hokey; it really was from the heart.

Orr will call her tomorrow (while I'll be traveling for work) to get more information about the study... are they really doing tree nuts? How long will the study take? Are they doing more than one nut at a time? Are there really spaces available? What is the process?  I'm getting picked up to head to the airport in 4 hours, but I can't go to sleep right now as my head is spinning. Each day we get new, important information, and it's all bringing us closer. To sweet dreams...