Category Archives: Artificial Pancreas

Clinical Trial: First Admission.

This is one in a series of posts detailing my participation in a clinical trial with an artificial pancreas element. I’m writing about this to chronicle my experience, and because if I were reading, I’d want to know about every aspect of what was going on. For more on this clinical trial, click here.

Last week, we reached the first admission for the clinical trial I’m participating in. This trial includes time hooked up to an artificial pancreas system. The AP system and the algorithm running on it was designed at University of California Santa Barbara, and is being tested there as well as at University of Virginia and the Mayo Clinic in Minnesota. As much as I can, I’m going to give you the play-by-play of everything that occurred over 48 hours or so from May 27th through May 29th.

The first thing I had to do was insert two Dexcom CGM sensors two days ahead of the admission. We needed to make sure there was enough time for the sensors to get calibrated, and for all of us to make sure things were working properly. There were two sensors because we needed one to work with the artificial pancreas system we were testing, and one as a backup, just in case. For the record, during the day and a half of closed loop testing, I had 2 Dexcom sensors and 2 infusion sets (one for the pump used in the trial, and one for my own) inserted around my midsection.

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Then I had to actually get there. That meant driving to Charlottesville Tuesday night, so I had time for my BG to calm down before the admission officially began on Wednesday around noon. I could have gone down on Wednesday morning, but the concern for me was that among the many guidelines (read: rules) in this study, I couldn’t be admitted if my BG was 250 mg/dL or over. My glucose level really spikes after I drive anything over two hours. Since Charlottesville is about four hours away, I went down on Tuesday night.

This admission (and next week’s too) took place at the research house that the Center for Diabetes Technology has in Charlottesville. It’s close to the university and the hospital, but a lot less clinical, and that’s nice. Anyway, after a comfortable night’s sleep and breakfast the next morning, I gathered with the other participant in this trial and the staff working on the first part of this admission.

We began with a BG check, then lunch. What a great way to start! About the meals: We could eat anything we wanted, including snacks, as long as they were under 90 grams of carbohydrates. The thing is, however: Anything we ate at last week’s admission (with the exception of potential hypo treatments), we have to eat during this week’s admission. Exactly. At the same time.

After lunch, the teams started the process of getting us hooked up to the closed loop system. We had to bring our own insulin, and it’s used in an Animas Ping pump for this trial. Good for me, since I’m still thinking about a pump change, and I hadn’t used a Ping before. Once we were hooked up to the pump, and I disconnected my personal pump, we went into another room while more team members completed the rest of the steps to get the closed loop system started. There are a number of detailed steps in the process. So many that a written “sequence of events” is followed.

All went well, and I was introduced to everything I needed to have in close proximity to me for the rest of my time there. This included a tablet that the artificial pancreas system ran on the entire time. But it also included:

– Insulin pump (of course)

– Receivers for the two Dexcom sensors

– My OneTouch Ultra2 meter to be used in the study

– Since it’s a Ping pump, it included the meter remote that’s usually used in conjunction with the pump. In this case, the meter remote was getting data directly from one of the Dexcom units, then sending the data to the AP algorithm loaded to the tablet. That algorithm was designed to take that data and use it to give micro boluses every five minutes during the trial. For this part of the trial, for me, something between .05 and .25 units at a time. Are you still with me?

– A phone. The idea of this phone was to be able to receive messages when my BGs could possibly get dangerously out of range.

I should tell you that the tablet had one of the Dexcom receivers (the non-backup) attached to it with velcro, and the meter remote was attached with velcro to the back. Here’s a shot of everything working together:

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Still, that’s a lot to carry around. Imagine having all of that with you, and having to have it in close proximity to you all the time. Including in the kitchen, in the shower,etc. I had a bit of exercise both days, and that meant someone on the team had to be with me with the tablet close enough to me to read the Dexcom and send insulin via remote. It was working right next to me while I participated in the Wednesday night DSMA Twitter chat.

Here’s what one of the screens looked like. The top number is my BG readings from the Dexcom sensor (the black part of the line are actual readings, and the blue part is predicted readings), and the bottom graph is the amount of insulin being doled out every five minutes during the same time. The red vertical bar in the insulin graph marks my bolus from lunch.

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As you might imagine, there were regular fingerstick BG tests throughout the admission. And every 15 minutes, night and day, someone was coming by to check my tablet and write down specific data.

Now, you might be thinking: Hey, this is crazy… Who, in real life, would put up with all of that? To which my answer is: This is a test of a system that is in development. It’s not the ready-to-take-home version of something you’ll be filing insurance paperwork for soon. At this point, I think they just want to see if what they’ve worked on so far is doing what they want.

I also realized that something like this, which in theory eliminates basal rates, requires a complete change in thinking. I can’t quite put it into words yet. I spoke a little with the doctor in charge of this testing, and between us, we understand that comparing the management of my diabetes with an AP system versus what I’m doing now is like comparing apples to artichokes. I came away with a completely different way of looking at my diabetes, and a fresh set of questions about what we need from a fully integrated artificial pancreas system once it’s ready for approval from the FDA. More to come next week!
 
 
 

Didn’t you mention something about a clinical trial?

Yeah, so I started a new clinical trial almost two weeks ago. This one, like the others, is being conducted out of the Center for Diabetes Technology at the University of Virginia, and also at UC Santa Barbara and the Mayo Clinic in Minnesota.

If you missed any of my other references, I’ll tell you straight out: This trial has an artificial pancreas element to it. That’s exactly how I’m describing it, because really, the trial is literally weeks worth of work by myself and others to prepare for about 36 hours on a closed loop artificial pancreas system. Here’s the sequence of events as I know it right now:

First, I went to Charlottesville to get screened for the study. This meant going through a physical, getting blood drawn for an A1c, having an EKG performed, the whole nine yards. We also went through the consent form (about 20 pages or so), and I submitted my medical history. This included things like confirming I was Type 1, that I’m not currently seeking treatment for things like alcohol or drug addiction, listing any hospital stays I’ve ever had, and listing out all of the medications I take on a daily basis, and in what amounts. The hardest part about these visits is that my BGs get so ramped up driving down to Charlottesville that I’m always running high when I arrive. The Jersey Turnpike has nothing on Interstate 81.

After the screening visit, I drove back home (more stress—I don’t know if I made it below 200 mg/dL all day) and waited for the phone to ring, telling me whether I had been accepted or rejected from the study. I had been rejected from two previous AP trials (different reasons), so I wasn’t holding my breath over this one. But I was accepted, and I was thrilled.

The following week I started a week of data collection by inserting a Dexcom sensor. I also started using a meter given to me to specifically be used for this trial. And I started keeping a daily diary. It included information on whether I was sick, whether I did a pump site or CGM sensor change, how I was feeling, how stressed I was about hyperglycemia and hypoglycemia, and whether I worked out that day. In addition, I needed to record times, BG fingerstick numbers, and carb counts of everything I put into my mouth. For an entire week. At the end of the week, I uploaded pump, CGM, and meter data, and faxed the daily diary info to the research team.

What was the purpose of all this? So the team at UVA could use my data to help build an algorithm specifically for me. When we finally get to the point where I’m hooked up to the closed loop system, the algorithm will work to help anticipate BG trends and carb intake, and make updates to insulin delivery as a result. Cool, yes?

So what’s next? Next are two separate admissions in the Center for Diabetes Technology’s research house in Charlottesville. I don’t know which visit will be which yet, but I do know that one of the visits will involve being on the closed loop artificial pancreas system itself, and one visit will not. The idea, as I understand it, is for the team to compare results on the closed loop system versus results from an open loop system in which I’m making decisions on my own, just like I do today.

My first admission is next week. Wish me luck! Actually, no… wish the dedicated team of researchers, developers, doctors and nurses luck. They’re doing the hard work of creating something that could be a game changer in terms of insulin therapy for people living with diabetes. Remember this: In all of these studies conducted, there have been zero overnight lows. My hope is that I can help further research into this and other advancements that are making the lives of the newly diagnosed better than I ever could have imagined at my diagnosis back in 1991. You and I are worth the effort.

I’ll try to give as much of a play-by-play account of what’s going on as I progress through the trial. Watch this space and Twitter for more.
 
 
 

I’m going to be a guinea pig.

Well, not a guinea pig really… but I am going to take part in a clinical trial. Where did that guinea pig thing ever start anyway?

Sponsored by the National Institutes of Health (NIH), the idea of this trial is “to assess an investigational simulation-based educational tool for persons with type 1 diabetes”.

Since the trial hasn’t started yet, it’s probably easier for me to tell you what I’ll be doing rather than what it’s all about right now.

When the trial begins, I’ll be starting on a Continuous Glucose Monitor (known to most of us as a CGM). It will be the Dexcom G4™, and I’ll be wearing it every single day for several weeks. During most of those weeks, I’ll be sharing data with the research team on a daily basis. I’ll be telling them about my CGM trends, my insulin usage, my diet, my exercise, how I’m feeling… the whole nine yards.

The information I’ll be giving will be used to fuel an algorithm that will be used to provide feedback so patients can potentially adjust insulin intake or make other adjustments, if necessary, to achieve optimal target BGs in the future. I guess the general idea is to see if an idea like this will achieve positive results. In the end, researchers want to find out if this tool “can be useful in diabetes management with the artificial pancreas system”.

I hope that explanation made some sense, at least. I’ve read everything about it a couple of times, and I’m still waiting for it to sink in all the way. What I can tell you for sure is that I’m very much looking forward to potentially helping other Type 1s through my participation in this study. As I go through the different phases of the trial, I’ll let you know more.

I went for my initial medical screening last week. Not having done this before, I can’t tell you that they are all the same. But I will share my experience on this occasion.

In advance of my visit, I had to complete about six pages of paperwork. Everything from doctors and emergency contacts to all the drugs that I take. You know, the usual. I also had to detail my pump’s basal settings and my insulin usage over the previous week. There were some additional questions in there that I probably shouldn’t share—not because they’re particularly personal, but because of the proprietary nature of the study. Nothing too shocking though. I also had to make sure I familiarized myself with the Dexcom™ online tutorials, so I’d have an idea of what I was getting myself into.

After I arrived and handed over my paperwork, I sat down with the clinical trial coordinator and signed a few important papers, answered a few questions, and asked a few too. After that I had a question and answer session with the endocrinologist working on the study. I don’t want to give short shrift to this part of the screening… there are important parts of the study that they’re covering in these meetings, and I was giving them information that they would need to determine if I was even eligible to participate.

Once I finished these two sessions, it was time to get my blood drawn. Again. Two weeks earlier, I had donated blood. A week earlier, I had blood drawn at my endo’s office for lab tests. And now I had to get blood drawn again for the study. It turned out that my Hemoglobin A1c result was 0.3 percent higher than it was the week before. Still in the good range, but WTF? Maybe they just didn’t take the blood out of the good arm this time. Whatever that means.

Finally, I met with the principal investigator on the trial. I got a basic explanation of the tasks I was expected to complete for the study. And we had a brief discussion of what I can and cannot blog about regarding this adventure. One of my basic rules applies here: When in doubt, leave it out. I’ll tell you as much as I’m sure I’m allowed to tell you without compromising the study.

Not having worn (or even seen up close) a DexCom™ unit, I’ll be looking for some advice on best practices. Got any ideas? Think about it and get back to me, if you can. The study will commence in about two weeks. Thanks!
 
 
 

#CWDTech 2013 Part One.

I’m a little late posting today… I stayed up late last night celebrating the Baltimore Ravens super bowl victory. Yay Ravens!

I didn’t get much sleep on Friday or Saturday either. The Great Spousal Unit and I were in Crystal City, Virginia (just across the river from Washington, D.C.) for the Children With Diabetes Focus on Technology conference. It was my first time at an event like this in at least a decade.

There is so much to talk about. I have to admit to suffering from a bit of information overload. Today, let me just talk about what I picked up from the sessions I attended. In part Two, I’ll try to cover interactions outside of the scheduled content.

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So let’s start at the beginning. The opening keynote was a dynamic talk from Dr. Ken Moritsugu, a former Surgeon General and Deputy Surgeon General who is now serving Chairman of the Johnson and Johnson Diabetes Institute. Dr. Moritsugu explained in great detail the importance of being an informed health consumer. There’s a lot of misinformation out there, and we need to do our best to separate fact from fiction. According to Dr. Moritsugu, it’s important to “access, understand, and use health related information to make sound, thoughtful health decisions”. What does that mean? It helps to remember three things:

1. Consider the source – Are you reading something from the Centers for Disease Control or World Health Organization, or is it from the “latest dream cure” website that promises much and delivers nothing in the way of information?

2. Risk is relative – Sometimes, a headline can grab our attention. But there’s often more to a story than just the headline. So when you see something like “Scientists find a link between breastfeeding and Type 1 Diabetes”, do the research. Was the scientific study realistic? Was it done on a large, diverse sample size, or did the subjects of the story come from a smaller subset of data that really doesn’t apply in the real world? Sometimes, the answers will surprise you.

3. Don’t forget to communicate with healthcare professionals – This is great for me. Sometimes my endocrinologist has additional information on something I just read about quickly online. Sometimes, she can go back and check things out if I have a concern about something, and then we’ll discuss it either in an e-mail or at my next appointment. Hopefully, you can count on having a two-way conversation with your healthcare professionals to hash out the truth and deception in stories about diabetes.

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Next we heard from Ed Damiano, PhD, who is Associate Professor of Biomedical Engineering at Boston University. He’s part of a large team working in Boston on bionic pancreas technology – known generally as the Artificial Pancreas. After visiting the University of Virginia’s Center for Diabetes Technology last year, I was interested in hearing the perspective of someone else working on the same technology. Let me tell you… it was no less fascinating. It was interesting to see the device they’re working with too. An iPhone (this is nothing new… UVA’s program uses an Android phone), with some cool characteristics. Among them are a bolus feature that doesn’t include a carbohydrate count. It simply asks you to say whether you’re eating a Typical Amount, Less Than a Typical Amount, or A Small Bite. The AP device does the rest. If something like this comes to market, carb counts could be a thing of the past. Is that crazy?

There’s more to this, of course. The team in Boston is still hoping for a better version of microdose glucagon to work in their dual-chamber device (which has already been approved for clinical testing). Tiny doses of insulin and glucagon are administered in the device to keep the patient in an appropriate range. Yes, there’s a lot more here that could probably take up an entire post, so I’m encouraging you to get more information on the work being done. When will something like this be available to all People With Diabetes? Right now, we’re looking at around 2017. And since that’s four years away, the timeline may still move a bit. But the progress so far is very encouraging.

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Got a chance to sit in a great discussion with Kerri Sparling and Scott Johnson that delved into Diabetes Devices in the Real World. People talked about everything from social media to carrying cases for your diabetes supplies to how you carry and show (or don’t show) your diabetes devices in public. It was a lively talk involving a variety of PWDs and parents who had lots of questions, but also lots of super information to share. People were creating Twitter accounts on the spot and showing off their D-bags. I loved watching faces light up when they started to understand something that they didn’t quite understand before, or found sources of information that they weren’t aware of prior to this get-together.

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Sunday morning’s closing keynote spoke volumes to myself and to Maureen. Sebastien Sasseville is the first Canadian with diabetes to summit Mount Everest. Not enough for you? Last year, he completed the self-supported Sahara Race in Africa, through the world’s largest non-polar desert, running 250km over seven days. He talked about both of these events and gave us some important insights. Most meaningful to me was when he talked about doing the Everest expedition. Over two months, their team had to start at base camp, then climb up to various camps before climbing back down again. They had to do this several times before making an attempt at the summit. The point was to acclimate the team to climbing at that altitude (can you really get acclimated to something like that?). The point is that while we have this constant “perfect diabetes management” goal in our minds, sometimes our path to that goal is filled with ups and downs that help us get used to what we need to make it all the way toward our ultimate goal. And what if we reach that goal: that perfect A1c, or perfect pregnancy with diabetes. What happens then? Sometimes, our goals change. Sometimes the bar gets moved. Both up and down. And that’s okay. And fear about the journey should not keep us from going after our goals.

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It was an interesting 36 hours or so. Soaking up a lot of information and hearing from people living the lives that we’re all living. Sometimes inspiring, sometimes life-affirming, sometimes funny. I’m lucky this was close enough that I could attend.

In part Two, I’ll try to cover my experiences outside of the scheduled sessions.
 
 
 

FDA Guidance on the Artificial Pancreas.

The latest FDA guidance is out on the Artificial Pancreas, and I’ve been taking a look to get a better idea of what it’s going to take to bring something like this to the market here in the USA.

I haven’t had a look at previous statements from the Food and Drug Administration on this issue, but after looking at the 63 page document recently released, I can tell you that it’s going to take a lot.

There are a number of reasons for that assessment, so let me see if I can break it down for you a bit. This isn’t a complete, detailed look, and I’m still seeking some other input on what some of the finer points really mean. For now, I’ll just try to give you some of the highlights.

When I think Artificial Pancreas, I think (like many others do) that we just need a device that will use data from our CGM to tell our insulin pumps what to do to help manage our glucose. Simple, right? Now, let’s think of everything having anything to do with that.

From the FDA’s point of view, that means anything and everything to do with your BG meter, your CGM, your insulin pump, and then your Artificial Pancreas device, which would probably be a modified phone of some sort.

If your meter, CGM, and pump have all been tested and approved before, great. Just provide all of the documentation that supports that, including the models, the way they each interact with each other, their adaptability to heat, cold, being dropped on the floor, your line getting kinked, getting wet, and on and on, ad infinitum.

Ready to move on to the AP itself? Okay, let’s talk about that. You’ll still need to detail how each piece of your AP system is going to work in a real-world setting. Detail how your device will interact with the CGM and pump, including how you plan to calibrate the CGM with each change, and how you plan to communicate that to the AP itself. Detail your algorithms, who they’re designed for.

Will the device be unidirectional (information moving in one direction only)? Or multi-directional (information moving between each piece of the system)?

A big question: How will the device combat hypoglycemia and hyperglycemia? And in that vein, will the device help in the proper delivery of just insulin? Or possibly insulin and glucagon? Or, as written here before, the delivery of insulin and amylin?

What about security? How can you ensure that the device won’t be hacked in some way? How can you be sure that the radio frequencies being used for the system won’t impede other systems? And while you’re at it, please detail how your system won’t be impeded by other systems like magnetic resonance imaging (MRIs), or even cell phones, computers, iPads, etc.

Once you’ve documented all of that, you can get down to the business of detailing the human factor. How will humans interact with your system? Will someone be allowed to override parts of your system? What about incorrect entry of key elements? What happens when someone leaves their CGM in “beyond the sensor wear period, when CGM results may be compromised” (actual language in the document)?

Now let’s talk about Clinical Study progression… including Early Stage testing, which includes proof-of-concept testing and studies regarding the effects of modifications to algorithms. Then later-stage feasibility studies, including some basic outpatient testing. After that, there’s “Studies to Demonstrate Performance of Risk Mitigation Strategies” (I think we all know what that means).

Finally, the Pivotal Clinical Study, designed to “gather data to support the safety and effectiveness of the device”. Real-world testing including individuals that the device is intended for. The patient population information detailed in the guidance on page 31, 32, and 33 is very important and worth the read.

Also worth the read are the very detailed Study Endpoints noted from page 33 through 35 that should include “objective characteristics or variables that reflect how a patient feels, functions, or survives. Surrogate endpoints should predict meaningful clinical outcomes and be based on valid scientific evidence”. This includes information on the use of CGM data, how the device handles hypoglycemia and hyperglycemia, how the device helps A1c results, how much the device helps the patient keep BG within range and what that range is, and how much time is spent within the range. Add in detail about safety mechanisms like low-glucose suspend and how high glucose and elevated ketones are dealt with. A final statistical analysis is expected.

But wait… you’re not finished yet. You have to include all of the documentation you intend to give the end user in:
– A User manual, written at an 8th grade level
– Training materials
– Professional documentation for prescribing physicians
– Package inserts for the AP device and any components that are packaged separately from the device itself
– Box and container labels for the AP device and any components that are packaged separately from the device itself

Don’t forget to describe how your device will be manufactured, including anything having to do with sterile parts of your system, if applicable.

And finally, you’ll want to include detail of the protocol of any Post-Approval studies you’ll want to conduct, assuming you’ll get approval in the first place.

That’s the very basic, 50,000-foot level view of what needs to be included in anyone’s application for an Investigational Device Exemption (IDE) or premarket approval (PMA) for their artificial pancreas device. That’s a lot, isn’t it? And to tell you the truth, I can’t find a whole lot in there that isn’t useful in defining how something will work, how it will be studied, and how it will keep us safe. But despite everything that’s necessary to bring this closer to the everyday patient, I’m still looking to the future with a hopeful eye. I’ll let you know if I find out more.
 
 
 

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