Time Capsule (or Capsule of Montelukast)

It is 11:31 pm on Monday, September 12, 2016.  My twins will be 11 years and 11 months tomorrow.  And I will undergo a gluten challenge at the University of Chicago Medical Center -- the last step before I will be officially enrolled in the investigational study of the efficacy of Montelukast in patients with Celiac Disease who consume gluten.  

I have taken two doses of the "study drug," which came to me by overnight mail on Friday, September 9, 2016.  The study drug capsules are clown-like in appearance -- big, puffy, red.  When I shake them, I hear something rattling around inside...and I wonder -- a tablet?  A capsule?  Or...what?  I have taken both doses, and just tonight I realized that it never even occurred to me to break the capsule open to check out what was inside...of course, even if it had, perhaps I wouldn't have known what I was looking at.

But, as I swallowed that big, fat, puffy red capsule on Sunday morning (the first day I took the "study drug"), I was struck by how truly odd it was to take a "medication" without knowing what I was actually ingesting.  That is very unlike me.
  

Believing in the importance of respecting in as many ways and as fully as possible the double-blind nature of the investigational study, after I took my first dose of the study medicine, I went about my day as usual.  A few hours later, I went to the bathroom.  After I finished, I was struck by the highly unusual foam in my urine.  I had done such a good job not thinking about the study drug that I stared into the toilet for a minute wondering what was wrong with me.  And then I remembered.  Study Drug.  Relief washed over me, for I suddenly felt certain that the foam in my urine must surely mean I had received the Montelukast (the drug being studied) and not the placebo.

I felt momentarily guilty -- how wrong was it that I would receive the drug being studied when Susan had not?  

And then I felt relieved -- that kind of relief that washes over you, weakening you in it's wake.  My upcoming gluten challenge would be fine.  As the fact that I was likely to be accepted into the investigational study slowly sunk in, I had had some terrible visions of what the gluten challenge might be like -- of it NOT being fine that the relief was almost overwhelming.  

And then I felt the burden of the secret -- if the study was to remain intact, double-blind and all -- I had to protect the information I had accidentally gleaned.  I was soso tempted to Google side-effects of Montelukast, feeling certain that I would find "foam in urine" as one of them.  But I wasn't going to do that.  Not then, and not ever.

I took my second dose of the "study drug" this morning, just after getting all three of our children safely to school.  Knowing i would be at the University of Chicago Medical Center for a minimum of four hours during and after my gluten challenge tomorrow, I was determined to make the most of my work day.  Before even taking the study drug, I made a list of things I had to get done.  There was a lot of work on the list.  I felt the volume of work on the list offset the fact that I would not be working the following day.

About 45 minutes after I took the study drug, I was struck by an overwhelming fatigue.  Not thinking about the study drug, I tried all my usual tricks -- I moved from my home office to my sun-lit dining room.  I drank a caffeinated beverage, and then I ate chocolate (yes, before 9:00 am!).  And then, when I found myself falling asleep in front of my computer, I took a brisk walk (I've been counting steps anyhow).

Ten minutes after I got back from my walk, I could barely hold my head up, and realized I was not getting anything done.  I gave in to the nap that was calling out to me (while I would LOVE to nap regularly, it just isn't something I do...pretty much not ever).  Unable to summon the energy to climb the stairs to the bedroom, I laid down on the sofa in our living room.  I set an alarm on my phone for 20 minutes, thinking Power Nap.

Three hours later, I woke from a deep, sound sleep -- hot, sweaty and with the feeling that I had slept through the day.  And, I sort of had.  I couldn't believe my eyes when I realized it was nearly time to pick my oldest up from school.  Still groggy, I ran through the shower and out the door.  Later, as I waited for her to come out of school, I marveled at my fatigue...and then was struck by a thought -- what if my fatigue was a side-effect of the Montelukast?  (A part of me wondered if I should have researched the side-effects of Montelukast before beginning the investigational study, but at this point, that is no longer an option...)   

As guilty as it made me feel to think that I knew I had received the study drug -- the Montelukast -- (for I am not supposed to know that), my intense fatigue also made me feel like things would likely be fine during my gluten challenge the following day...

Uncontrolled Celiac Disease

The real answers slid silently in overnight, their arrival announced by two distinct e-mails time-stamped three minutes apart from the University of Chicago’s MyChart e-mail address. 

Again, I hurried to access the hospital’s MyChart system.

When I clicked on the first lab report, for Gliadin IGA AB, the word “POSITIVE” jumped out at me.  I saw a value of 32, with a reference range in which anything over 20 was positive.

Remembering I had seen lab results for the same test after my intake visit on August 17, 2016 for the investigational study, I quickly pulled up those results.  NEGATIVE, with a value of 15. 

I marveled at the difference nine weeks -- six of them with daily doses of gluten -- had made.

And then I moved on to the next set of lab results, for Tissue Transglutaminase IgA.

POSITIVE.

Positive...with a value of 99, and a reference range in which anything over 30 was positive. 

Feeling fairly certain that the lab results for this test after my intake visit in August had also been negative, heart pounding, I quickly found them in my on-line chart and opened the results from the blood draw on August 17, 2016.  Negative, with a value of 15.

I checked in with Dr. Google, wanting to better understand the particularly high value for the Tissue Transglutaminase IgA test and was not surprised to read that such a high number is strongly consistent with “uncontrolled Celiac Disease.”  As I read on, I found several scholarly research articles that suggested a value of 99 or higher could result in a diagnosis of Celiac Disease without biopsy.  That's how conclusive such a high number is.

   

Incredible.

None of what I had been feeling was in my head...and it happened in just SIX weeks.

I tried to process what it all meant, and kept coming back to what I had been saying for a while.

Either the study drug (Montelukast) had not worked for me, OR I had received the placebo.

And while I suspected the odds of my having received the placebo were low, I felt certain that that's what I hoped had happened.

We know Susan received theplacebo in her clinical trial for her peanut allergy.  She was one of 9 subjects at her study site, two of whom received placebo. 

I would never expect the universe to protect me from receiving the placebo just because Susan had, but I will admit that I did think the odds of me receiving the placebo in the investigational study (12 subjects, 4 of whom received placebo), had to be pretty low, given that Susan drew the proverbial "short straw" back in February of 2014.

But how low?

Well…the social worker in me wasn’t entirely sure how to do the math…but I thought it was likely a function of understanding Susan’s odds, my odds, and then multiplying the two.  7.4%.  No.  Really?  

Just to be sure, I threw the question out to a group of VERY smart college classmates, one of whom (Anna Prescott!) provided this answer:

Pm = Placebo mom

Pd = Placebo daughter

Probability of Pm AND Pd = 2/9 * 1/3 = 7.4%

Probability of NEITHER Pm NOR Pd = 7/9 * 2/3 = 52%

Probability of Pm but NOT Pd = 7/9 * 1/3 = 25.9%

Probability of Pd but NOT Pm = 2/9 * 2/3 = 14.8%

Probability of EITHER Pm or Pd but NOT both = (2/9 * 2/3) + (7/9 * 1/3) = 40.7%

And so, my mathematician classmate arrived at the same answer I had (although with greater fanfare):  7.4%

Incredible, really.*

As I mulled that small number over, I scanned the lab results and e-mailed them to a friend.

And I waited.

And I waited some more.  I wasn’t sure she was up, and I didn’t want to wake her, but I wanted someone else to look at what I was seeing and assure me I wasn’t…crazy.

Eventually, she sent me a text message.

She had been busy with Dr. Google herself, and she was upset -- struggling to see how it could be acceptable for me to have participated in a study that would have made me...so sick.

While I wish that hadn't happened, I find myself thinking exactly what I thought when Susan was in her clinical trial -- maybe this happened for a reason.  Maybe my participation will yield key data that will help researchers moving forward.  

As for me, I'm back to a strictly gluten free diet, and I don't miss my daily gluten doses of Cisco wheat bread (which I ate toasted and buttered almost every day).  I don't feel as much better as I thought I would -- whenever I eat, my stomach hurts.  And therefore, I'm not eating as much as I used to, but when I go too long without eating, I don't feel well, either.  Dairy, previously a staple in my vegetarian lifestyle, has become a trigger for severe gastrointestinal distress.

I know it can take months for villi to fully heal, so I am practicing patience.  I'm relatively confident that with time, my digestive system will heal.  Eventually, eating will not be synonymous with intense abdominal discomfort.

And maybe, just maybe...in time...there will be a treatment...or maybe even a cure.  If I brought researchers even one tiny step closer to answers, I am beyond thankful to have been a part of the process.



*(Editing to add that another classmate of mine, Ann Russey Cannon, posted the following comment in response to my post which read, "I want to explain your probabilities a bit more.  If we were looking ahead to both you and your daughter participating (in the future) in the two clinical trials, then the probabilities that you calculated were, indeed, correct.  The probability that both of you would receive the placebo was 7.4%.  But since the two trials were independent - that is knowing whether your daughter received the placebo or not wouldn't affect whether you did or not - the probability of you receiving the placebo, knowing that she did, is 1/3.  And the probability of you receiving the placebo knowing that she didn't, is 1/3.  That is, the probability that you would receive the placebo was always 1/3.  And that isn't a particularly small probability.  Sorry.")  

After my classmate posted this comment, I pondered it, and after thinking about it, it made sense -- sort of.  A while later, I replied with a comment that this is exactly why I am a social worker.  As the day wore on, I found myself thinking that maybe this actually makes me feel...better.

NOT All in My Head ("Normal" is All Relative)

While I’ve tried hard to not complain as the weeks of the investigational study have worn on, the truth of the matter is that I really haven’t felt well -- at all.  I will be the first to say that I know it could be worse -- I could be dealing with far greater health issues than those I brought upon myself by volunteering to participate in the investigational study.  And…I could be dealing with chronic health issues that are unlikely to ever improve.  I have a fairly high degree of confidence that I will start to feel better now that I have returned to a strictly gluten free diet.  It is for these reasons that I have tried not to complain.

I think those who have followed along closely have a pretty good sense of the fact that the investigational study has taken more out of me than I anticipated.

Since I decided early on not to try not to complain, I haven’t talked that much about the investigational study -- or about how I feel.  But, every now and then, someone asks specifically.  And in those instances, as in my blog, I have tried to answer specifically and openly and honestly. 

A few days ago, someone I hadn’t seen in a while I asked me how things were going with the investigational study.  It was clear that she had a vague understanding (or maybe a bit more) of what the investigational study had involved, but it also became clear relatively quickly that she did not really have a good sense of just how hard it has been.

It gave me pause when, after I explained that I had gotten to the point that I was feeling much like I had felt prior to my diagnosis with Celiac Disease, she asked if it was possible that it was all in my head.  I don’t think she was trying to be difficult, or to discount what I was saying -- I actually think she really wanted to know.  

As I considered her question, I realized that at one point, I, too, had questioned whether or not my symptoms (or some of my symptoms, at least) might be in my head.  That feels like a million years ago now…and is a thought that slid slowly, seamlessly from my mind in the face of debilitating fatigue, shortness of breath on a single flight of stairs and an ever-present lightheadedness and unsteadiness that left me feeling as though the center of my world was ever-so-slightly off-axis.

At some point, another voice took over, counting down the gluten doses, encouraging me, reminding me that there is a child much like my own daughter out there who needs a treatment for Celiac Disease just as desperately as Susan needed a treatment for her peanut allergy.

I'm pretty sure I got briefly lost in my own thought, and when I returned to the conversation, I could tell my friend's interest was waning, so I simply shrugged and agreed that yes, it was possible that it was all in my head.  And I thought -- maybe it IS all in my head.  After all, anything is possible.  But, I really didn’t believe that any of it was “in my head,” and the lab work results that were waiting for me when I got up one morning earlier this week further suggested that none of what I have been experiencing is in my head.

It was 5:00 am, and I was up with my oldest daughter, who rises at the insanely early hour of 4:30 am every day so that she can skate before school, when I sat down to check my e-mail.  I saw two separate e-mails that came in just minutes apart from the University of Chicago's MyChart e-mail address.  Not being sure what to expect, but very interested, I quickly logged into the hospital's MyChart system.  

I opened the results of the CBC with Differential and Platelets and the Comprehensive Metabolic Panel (CMB) and with my still-foggy morning brain, I quickly scanned the results, looking for results that fell outside the normal range.  Nothing.  Nothing?  I couldn't believe it.  How was it possible that I could feel so unwell and all of my lab results could still be within normal limits?  

And then, in a moment of clarity, I realized I should compare my lab results from the blood draws taken during the investigational study intake to my current lab results.  And in doing so, I saw changes that I felt relatively certain were...if not statistically significant...at least relevant.

My total blood cell counts -- for both white blood cells and red blood cells -- were down, which is suggestive of blood loss, internal bleeding.  My white blood cell counts, which were initially 5.3 (with a normal range of 3.5 - 11.0), were at the very bottom of the normal range, at 3.5.  My red blood cells, which were originally on the high end of the normal range (3.88 - 5.26), at 5.01 had dropped to 4.71.  Not surprisingly, my hemoglobin had also dropped, from 13.9 to 13.1 (normal range is 11.5 - 15.5).  While definitely not anemic (yet), my total blood cell counts definitely were moving toward values that would lead to a diagnosis of anemia.  And maybe, just maybe this helped explain my extreme fatigue.

I also noted that my eosinophils had increased from 2% to 6%.  With a normal range of 0 - 7%, it seemed likely that such an increase was truly statistically and maybe even medically significant, and given that I know that elevated eosinophils can be indicative of allergic reactions and/or other forms of inflammatory autoimmune responses, I thought that result just might be significant.

And then, for the first time since starting the investigative study, I decided it was time to visit Dr. Google for some help in assessing a related value in the same section of the results -- neutrophils.  I noted that my neutrophils had decreased, from 63% to 47%, with a normal range of 39% to 75%.  It struck me that that was a big decrease, and I could not help but notice how close my current result was to the low end of the normal range.  And so, I googled “low neutrophils.”I learned that people with low neutrophils often have difficult fighting off infection, which made sense given the cold I got early in the investigational study that I hung on and on, and on.  And then I went a step further and googled “causes of low neutrophils.”  I discovered that there are many causes of low neutrophils, including...Celiac Disease.  Ah, I thought...

Later, as I was leaving for lunch with a friend, I tucked the lab results into my purse.  My friend has a lot of medical expertise, and I found myself thinking it might be interesting to see if she saw the same things I did...and she did.  

Which left me thinking that surely, it must NOT all be in my head...

She Needed a Hero,

...so that’s what she became.

Like much of my time in the investigational study, the day of the endoscopy -- the last big hard part -- was not quite what I expected.  My endoscopy was scheduled for 7:30 am at the University of Chicago (a solid hour from my house).  Since I was to be there an hour before the procedure, my husband and I left our house around 5:15 am. 

I was tired, but having done the whole endoscopy thing before, I thought I knew what to expect.  I envisioned a softly sleepy day following the procedure -- the edges of my responsibilities slightly blurred, the urgency of my never-ending “to do” list fading while I rested, slept, and read (I had not one but two good books waiting for me).  I figured it did not matter that I was tired, as I felt certain I would “catch up” on my sleep later in the day.  Little did I know that I would lose giant chunks of the day at a time…

We arrived at the hospital with time to spare.  I was escorted to the outpatient surgery preparation bays, where I was prepared for "the" procedure.  The investigational study coordinator arrived just as they were inserting my IV and requested that they draw blood for the study concurrently.  With my empty Ziplock baggies and prescription bottle in one hand and my stool sample and the six vials of my blood in her other hand, she nearly danced off -- thanking me profusely as she left.

In the holding bay, I talked to a very kind Indian Fellow (read:  fellow/resident) with an awesome accent and a name I knew I would never be able to pronounce.  He was clearly new to this particular rotation.

So, you are here for an Upper Endoscopy?

Yes.

You think you have Celiac Disease?

I know I have Celiac Disease.

Ahhh.  So you follow a gluten free diet.

I was following a gluten free diet until I started eating gluten six weeks ago.

Oh…?

Yes, for the investigational study.

Oh (with eyes slightly bugging out)…and so how do you now feel?  Not so very good?

I haven’t felt great…

He grinned at me -- filling my silence with a very accurate summary of how I have been feeling.

As the nurse wheeled me toward the operating room at about 7:20 am (early!), she double-checked that I had seen the doctor, that I had had a chance to have all of my questions answered.  I assured her that I was fine -- explaining that I had seen a male “resident” (my term).  She was puzzled as to who that would have been until the Fellow walked into the operation room, at which point she connected the dots, saying, “Oh, here’s your mystery fellow!”  We all giggled just a little…

The doctor running the investigational study breezed in a few minutes before 7:30 am, paused for a moment, looked hard at me…and said “You’re done!  You gutted it out!”  And then, holding my gaze, she very seriously thanked me.  I sort of shrugged.  While the investigational study has not been easy, I never really entertained the idea of an early termination (read:  “quitting.”). 

As the team made final preparations for procedure, the doctor reviewed the plan -- explaining that they would be taking a number of biopsies of my villi.  Just as I was starting to feel the first effects of the anesthesia, I heard the doctor say something about additional biopsies.  Someone in the room asked about it, and she said something about cold tongs, or something...and the last thing I remember hearing is her reassuring them that she would take those biopsies.  I'm thankful I don't remember anything else, for I know enough about what happens to know that I could remember more.  

The next thing I knew, it was 9:36 am.  I had assorted random bits of information floating around in my head -- extra biopsies, cold tongs…some pieces of the conversation my husband had with the doctor about how everyone in the study had had some symptoms, about how they had selected candidates they thought would be able to tolerate consumption of gluten without the protection of the study drug…and this vague feeling that somehow I had lost time (previously I have been in recovery and awake and preparing to leave within an hour of the start of the upper endoscopy).  Later, as I tried to piece together my experience and what I had heard with a friend, I had to smile when she said, “I always think it’s funny that the doctor talks to you when you’re wasted.”  Yes.  That.

…and then, before I was even fully awake, the nurse removed my IV and said we were free to leave.  I can only surmise that she offered me a wheelchair because I was having a hard time staying awake, but since the offer of a wheelchair was unexpected, I declined it.  I walked unsteadily toward the parking garage with my husband, who ultimately suggested I wait on a bench for him.   

The next thing I knew, my husband was rousing me, encouraging me to get in the car…and then the next thing I knew, I was home…and fighting nausea and an excruciating headache that was obscured, thankfully, by giant chunks of time that…simply fell away.  

It wasn’t until about 9:00 pm that evening that I was even able to articulate to myself that the day had not even remotely had the softly sleepy quality to it that I had anticipated, that I was indescribably more tired than I had been after what was essentially the same procedure only eight weeks earlier, that I was miserable...that something about this experience was different.  

That was Thursday.

Maybe, a friend later suggested, it was so hard because your body was on edge already.

  

Friday was nearly equally as difficult…and somehow, I lost sight of the fact that the biggest hard part of the investigational study really was behind me.  And then a dear friend stopped by with a gift -- a small tray that read “She needed a hero, so that’s what she became.”  I loved the sentiment, but I wasn’t sure it fit me.  Maybe that’s because a tiny voice inside my head has wondered, all these weeks, if -- just maybe, some part of it all was in my head.  

As results -- first blood, then biopsy -- have started to trickle in, sliding silently into my e-mail under cover of night, I’m starting to think I just might have to endorse the idea that something heroic happened here.

Stool Sample (or TMI 3)

Earlier this week, I wrote "I'm not done, but the biggest hard part is behind me."  Since then, I have pondered the veracity of that.  In some ways, it is very true.  

But, as I found myself thinking earlier today, in other ways, "the biggest hard part" isn't yet quite behind me...

Today's agenda included collecting a stool sample.
And on tomorrow's agenda is a blood draw and an early morning upper endoscopy...

Yes, there are definitely still some hard parts left to do.


Prior to my participating in the investigational study, I had never collected a stool sample.  For anyone who has never done this, let me just say that the process of collecting a stool sample allows for a special kind of intimacy with one's stool.  I didn't particularly enjoy the process of collecting my stool sample back in August, and I was definitely not looking forward to doing it today.  

In fact, the whole chronic abdominal pain, constipated, not constipated (read: frequent and often unexpected diarrhea -- but only at random times) thing made me sort of nervous.  (How could I collect my stool if I had little control over my next bowel movement?  Worse -- how would I collect my stool if I simply never had a bowel movement today?)  So, while I wasn't nervous about collecting my stool...I was decidedly nervous about whether or not I would be able to capture the stool today that I needed to collect to turn in tomorrow.

And so...I decided to stick close to home as much as possible this morning...and hope for the best.

I drank a lot of water, and I hung out.
And I waited.

And I got nervous, because while my stomach really, really hurt, I wasn't sure anything was going to happen while I was home.  And the thought of trying to collect a stool sample while out and about -- well -- no words.


Eventually, just when I was about to resign myself to having to schlep my stool collection kit along with me, I really did have to go.  And what I observed while collecting my stool prompted me to write about this very intimate experience.

For the uninitiated, the process of collecting a stool sample allows one a first-hand look (and smell) at one's stool.  It also allows one a special sense of the consistence of one's stool.  And my stool sample from today was decidedly different than the stool sample I collected eight weeks ago -- far smellier, far softer and looser, and with large undigested bits of food.  While I was not really surprised that it was different, I did not expect it to reveal quite so much...


For now, the three test-tubes are safely tucked away in a brown paper lunch bag in my refrigerator. 

I don't know for sure what they will reveal, and while I won't know for some time whether or not I was one of the four controls in the 12-subject investigational study, I feel I can say with confidence that if I was not one of the controls in the study, this particular protocol (Montelukast) did not work for me.

And if I have learned anything?  It is that there is a tremendous need for a cure, a treatment...something.

Chronic Abdominal Pain...

and bloating, 
and diarrhea 
and constipation...
  (yes, oddly enough...both)


As much as I wish I had sailed through the investigational study without a single complaint, that is not the case.  While I won't know for some time whether or not I was one of the four controls in the 12-subject investigational study, I feel I can say with confidence that if I was not one of the controls in the study, this particular protocol (Montelukast) did not work for me.


I consumed my last dose of gluten this morning, making today the 42nd straight day I have consciously consumed gluten after having seriously and purposefully avoided gluten for 1964 days (I was diagnosed with Celiac Disease on April 27, 2011, and have been gluten free ever since).

Late last week, I suddenly realized -- while fighting nausea and breathing deeply through waves of dizziness and holding tightly to the railing while descending stairs as the edges of my vision grayed and tiny pinpricks of light danced in front of me -- that I feel very much like I did before I was diagnosed with Celiac Disease.  

The realization struck me hard, like a run-on train.

Incredibly, while I have known (really, since the beginning), that I haven't felt well, the symptoms and complaints have slowly compiled until -- staggeringly -- if I can trust my memory, I feel at least nearly as unwell as I did before I was diagnosed with Celiac Disease...if not more unwell.

...if not more unwell.

Because, on top of the symptoms I once had -- including extreme fatigue, to the point that I could not climb a flight of stairs without pausing, without gasping for breath -- I now have new symptoms -- gastrointestinal symptoms that threaten to rule my life.


I was feeling like it was hard to explain how I feel until I realized earlier today that I know exactly how to explain how I feel.  Much as there is a very specific pre-vomit pooling of saliva that occurs under one's tongue, there is also a very specific post-stomach flu shakiness and unsteadiness -- that wrung-out feeling -- that hangs on until one is properly rehydrated and until one has eaten something solid.  That is how I feel.  But, that post-stomach-flu wrung-out feeling isn't a short-lived -- just until I drink and eat and maybe sleep a bit -- feeling...it is nearly constant...hanging on, ebbing and flowing, but always there.

And really, it makes sense.  

These days, life with my stomach goes something like this:

My stomach hurts.

I am getting (or have) a headache.

I might be hungry -- but nothing sounds good.  Nothing is appealing.
  (Just thinking about some foods even makes me nauseous.)

And I know...from previous recent experience...that while I might be both hungry AND experiencing a stomachache...eating is likely to resolve only one of those complaints...while worsening the other.

But I also know that I cannot simply not eat, and so...eventually, carefully, planfully...I eat.  And incredibly, sometimes eating is fine...sometimes I even feel better for a short while...whereas other times, eating results in severe abdominal pain and gastrointestinal distress.  And the worst of it is that I never know what to expect.

I picture the villi lining my small intestines damaged and angry, unable to do the job they are there to do, and I wonder what the doctor will see during my upper endoscopy later this week.  And yet, I think I already know the answer.  I expect she will will tell me that she cannot tell anything without a microscopic examination of the ten biopsies she will take.  It is staggeringly hard to believe that it takes a microscope to see the kind of damage I expect has occurred...and yet, I have traveled this road before.

Fortunately, my last dose of gluten is behind me.  Healing -- while likely indiscernible -- will have begun before my upper endoscopy even takes place.

I'm not done, but the biggest hard part is behind me.

And if I have learned anything?  It is that there is a tremendous need for a cure, a treatment...something.