Clinical Study Review: Metabolism in Friedreich’s ataxia (FA)

Recently I volunteered for a study with Dr. Shana McCormack at the University of Pennsylvania (UPenn) in collaboration with The Children’s Hospital of Philadelphia (CHOP). Dr. McCormack is an “Endocrinologist”, which means that she studies the how our bodies’ hormones control various and important bodily functions, such as: sleep, metabolism of food for energy generation, our mood, our growth and development, for example.

During my participation in this study, I thought about the difference between a “clinical study”, and a “clinical trial”. Dr. McCormack was not testing a new therapy (i.e., clinical trial), but was instead studying a feature of FA with the goal of enhancing our medical knowledge of the disease (i.e., clinical study). Armed with this knowledge, clinicians and researchers are empowered to develop better treatments for FA. The natural history study, for example, is a clinical study that has greatly improved our understanding of FA disease progression, and has positively influenced how Pharma companies design FA clinical trials. Just like when I volunteer for a clinical trial, I am confident that my participation in Dr. McCormack’s clinical study is getting us closer to treatments and a cure. 


Asking Questions, Getting Answers

Dr. McCormack is interested in FA because it is a multi-system disease, affecting many different organs of the body. One of the affected organs is the pancreas, the organ in our body that helps regulate how all the other organs take up nutrients from the food that we eat. To do this, the pancreas produces many hormones that serve as a on/off switch for nutrient uptake, including the hormone insulin. Insulin aids in regulating sugar metabolism in the body. As we know from the world today, dysregulation of sugar metabolism can result in metabolic disorders, such as diabetes and obesity. FA can also affect muscles, which can impact sugar metabolism also, because healthy muscles use up sugar for energy.

Given that ~10% of individuals with FA develop diabetes, and many more have pre-diabetes, one of Dr. McCormack’s research objectives is to understand whether FA can make the pancreas misbehave in a way that makes it function like a pancreas in someone who has diabetes. One of Dr. McCormack’s other research objectives is to understand more broadly how whole body metabolism in FA works, and whether it behaves like a normal or unhealthy metabolism. The results of her study, as I alluded to above, will contribute to our overall understanding of FA, providing key insights into future FA therapies. Also, it may be that some medications already in clinical use for diabetes may improve metabolism in people with FA, and thus improve their overall health and the course of their disease.

And so, the design of Dr. McCormack’s clinical study is to compare the metabolism of someone with FA to (1) a person who is otherwise healthy and of normal weight, and (2) a person who is obese.

My Experience as a Study Participant

The clinical study notice came from the FARA patient registry, and admittedly it sat in my inbox for several weeks until I finally sent an email to see if there was still need for volunteers.

To assess if I was eligible for the study, I first had a pre-screening phone call with Dr. McCormack’s study coordinator, Sara Nguyen. Sara asked me some simple questions that helped her confirm that I was a good fit for this study. Plus this study required an overnight stay in the hospital, so I had to make sure to choose dates that worked with my schedule.

2 weeks before my study dates, Sara emailed to let me know that I needed to discontinue the use of certain vitamins and supplements. She also sent me a diet log to be completed each day for the three days prior to my visit. I had just started a nutrition challenge at my gym (800 grams of fruits and vegetables a day!), so I felt pretty good about the diet log. The diet log gives a snapshot of a person’s eating habits, which allows Dr. McCormack and her team to determine if my diet will play a role in how my body’s metabolism performs during the study.

The day of the study, Sara met me in the lobby at the hospital and our first stop was a brief meeting with Dr. McCormack. Together, we went through the consent form and the schedule, and Dr. McCormack helped me understand her research questions and the goals of the study , and how that understanding would contribute to greater knowledge and insights about FA. We also talked about cycling, exercise, the upcoming Super Bowl, and the Two Disabled Dudes Podcast -- of course!

Up next, I had my body imaged by the “DEXA scan”. This really cool machine measures the body’s composition of fat, muscle, bone etc. These measures will help Dr. McCormack assess wahether the metabolism of an individual with FA influences, or is influenced by, our body composition. 

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At 5pm, I had an MRI scan, which was focused specifically on the calf muscle. I put my right leg in this little tube with a pedal at my foot. I laid on the table as it slowly went into the MRI machine, so that my chest down was in the tube while my head was sticking out. Sara’s voice came over the intercom and she told me to press the pedal with my foot to the rhythm of her counting. After pressing the pedal for 90 seconds, I then laid still while the machine made noise and did its thing. This MRI measures how quickly the muscle recovers after exertion. This information will help Dr. McCormack and her team better understanding how the muscle of an individual with FA metabolizes energy for muscle movement.

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Calf Muscle MRI Scan

What happened after the calf MRI scan? Dinner time! The spaghetti and meatballs dinner did not fit in the nutrition challenge of 800g of fruits and vegetables per day, but it was pretty good so I indulged a bit. I needed to carb load for the long day of blood draws that happens with this study.

There was no monitoring during the night, so I slept like a baby. The overnight stay is required so testing could start right when I woke up and to standardize eating, sleep, and activity before metabolic testing. So the nurse woke me up at 6:30am to put an IV in each arm.

After a baseline blood draw, I did the first of 3 resting energy expenditure tests, which were 30 minutes during each test. “Resting energy expenditure” is exactly what it sounds like - how much energy my body uses when I’m at rest.

During this test, they use a hood that makes it look like you’re going deep sea diving, to measure all the gases that go in and out of your body while you are at rest. This measurement of the oxygen that I breathed in and carbon dioxide that I breathed out can be used to determine how much energy my body used up as I sat at rest under the hood.

Fortunately, the hood is clear, so I was able to work on my computer during the 30 minute test.
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Resting Energy Metabolism Equipment

After the first energy expenditure test, around 10am, I started a glucose tolerance test. Remember when I told you about how the pancreas makes the hormone insulin, which tells the organs in the body to take up the sugar from what I eat? Well, we put my pancreas to the test!

Dr. McCormack wanted to see how quickly my body produced insulin and how quickly my body used up the glucose, so, I drank this small bottle of sugary liquid that tastes like flat orange soda, and then Dr. McCormack’s team started periodic blood draws (no new holes in my arm, just blood drawn from the IV they hooked up that morning). At first, the blood draws were 10 minutes apart; and then over the next 4 hours they ended up at every half hour.

At 3pm that day I was free to go. Dr. McCormack and her team had collected all of the data on my body’s metabolism, and Sara sent me home with compensation and a small monitor stuck to the back of my arm that measures blood glucose every 15 minutes without me knowing. I would mail the device back in 14 days in a postage-paid and pre-addressed envelope.

Now they will find two age-matched controls (one healthy and one obese individual), and compare my study results with the results from these controls. These data will allow Dr. McCormack to understand if my metabolism behaves more like a healthy individual or an obese individual, or something else entirely. What’s really neat is that my (de-identified, of course) study results will be published in a medical journal in the future, contributing to our overall understanding of metabolism in FA. In the nearer-term, it also helps Dr. McCormack and other endocrinologists choose the right treatments for pre-diabetes or diabetes when these develop in individuals with FA.

It’s exciting and clear that these study results will indeed take us closer to the ultimate finish line, treatments and a cure for FA.

Everyone Plays Their Part

As patients we tend to think that clinical trials on a specific drug are the only way to participate. And then, if we are excluded from a clinical trial because of age, heart function, existing medications or any number of other exclusion criteria, it is a frustrating and discouraging experience. However, there are many clinical studies that are not necessarily testing specific drugs that need our participation! With clinical studies, the inclusion/exclusion criteria are often not as restricting as clinical trials and the studies lead to conclusions that are just as valuable as clinical trials because they provide key insights on ways to to develop new treatments and enable more clinical trials.

It is clear that our ultimate goal is an approved therapy that improves the condition of those with FA. But research is a complicated thing. It almost seems like an abstract concept sometimes. There are many people involved and many moving parts. If any of those parts are missing the whole system fails.

Clinical studies provide the needed insight to enable clinical trials but these studies never happen without willing participants.

Don’t underestimate the power of your participation.

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