Esophageal String Test: Monitoring Tool Use and Development

Description:

Co-host Ryan Piansky, a graduate student and patient advocate living with eosinophilic esophagitis (EoE) and eosinophilic asthma, and Holly Knotowicz, a speech-language pathologist and feeding specialist living with EoE who serves on APFED’s Health Sciences Advisory Council, talk with Drs. Robin Shandas and Steven Ackerman, are scientists who work together at EnteroTrack.

In this episode, Ryan and Holly interview Drs. Shandas and Ackerman about the development of the esophageal string test (EST), or simply the string test. They discuss the initial concept and the work that led to the development of the string test to collect samples from the upper gastrointestinal mucosa. The test involves swallowing a capsule, similar in size to a TicTacⓇ, with a string attached. It began as an overnight test, and today is a one-hour test. During the conversation, the researchers explained the use of the string test as a monitoring device for EoE, not as a diagnostic device. They describe how the test is administered with no endoscope, no anesthesia, no recovery time, and only minor discomfort for some patients. They discuss the age range for using the device (as young as 4) and the advantages it offers over traditional endoscopy and biopsy for frequent monitoring of eosinophilic esophagitis. Finally, they advise patients on how to access the test: Ask your clinician about it!

 

Disclaimer: The information provided in this podcast is designed to support, not replace the relationship that exists between listeners and their healthcare providers. Opinions, information, and recommendations shared in this podcast are not a substitute for medical advice. Decisions related to medical care should be made with your healthcare provider. Opinions and views of guests and co-hosts are their own.

 

Key Takeaways:

[:50] Co-host Ryan Piansky welcomes co-host Holly Knotowicz. Holly introduces the topic of a new unsedated diagnostic tool for EoE, the esophageal string test, or for the purposes of today’s podcast episode, the string test.

 

[1:34] Holly introduces Drs. Robin Shandas and Steven Ackerman, are professional scientists who work together at EnteroTrack. Dr. Shandas is the Chief Executive Officer and Dr. Ackerman is the Chief Science Officer.

 

[1:48] Drs. Shandas and Ackerman, with a team of entrepreneurs, engineers, medical doctors, and scientists, developed the EnteroTracker®, the esophageal string test, a new method for collecting and sampling upper gastrointestinal mucosa.

 

[2:00] Holly thanks Drs. Shandas and Ackerman for joining us today.

 

[2:19] Dr. Ackerman has worked on the biology and the roles of eosinophils in the pathogenesis of allergic diseases, including asthma, eosinophilic gastrointestinal disorders, and other hypereosinophilic syndromes for the past 40 years, starting when he was a post-doctoral fellow at the Mayo Clinic in Rochester, Minnesota.

 

[2:44] About 18 years ago, Dr. Ackerman transitioned his lab to do more clinical translational research in eosinophilic GI diseases. His lab developed and validated the string test and the biomarkers and immunoassays that they use to evaluate the results.

 

[3:10] Dr. Ackerman was also interested in studying how the eosinophil participates in tissue remodeling and fibrosis of the esophagus in EoE and other eosinophil-associated diseases. Notably, this started with a small research grant from APFED in 2007 to 2008, which was followed by a more substantial APFED grant in 2011.

 

[3:51] Ryan was involved in APFED in 2007 and he remembers hearing about the early work that was going on for this new test. He thought it would be fantastic to have a test without anesthesia or a scope down his throat. It was exciting to hear about the development over time.

 

[4:23] Dr. Ackerman and Dr. Glenn Furuta, a pediatric gastroenterologist, initially conducted eosinophilic disease research together at Harvard Medical School. Dr. Ackerman eventually went to Chicago but continued to interact with Dr. Furuta. They published papers together on eosinophils and their roles in GI diseases.

 

[4:47] Dr. Ackerman was inspired to develop the string test when Dr. Furuta pointed out to him the tremendous need for a minimally-invasive or non-invasive test for EoE that would remove the need for children to have multiple repeat endoscopies and biopsies under sedation.

[5:11] The endoscopies and biopsies were done to follow patient responses to treatment, especially food elimination diets. Dr. Ackerman’s goal was to provide a way to evaluate disease activity in children with EoE in a minimally invasive or non-invasive fashion.

 

[5:42] Dr. Shandas is a biomedical engineer, entrepreneur, and educator. He has been a scientist for over 30 years. He is a Distinguished Professor of Bioengineering at The University of Colorado. His passion is to take ideas that he thinks can help people and go through the work. It’s really, really hard work to bring those ideas to the clinic!

 

[6:07] Dr. Shandas has been working on the string test for some time. He started eight companies to support this type of activity. The idea of the string test, a simple, non-invasive way to collect samples from the esophagus to support frequent and granular monitoring of disease activity, was compelling when Drs. Furuta and Ackerman presented it to him.

 

[6:38] After Drs. Furuta and Ackerman received funding from APFED they did a lot of basic science research to develop the foundation of the string test. They approached Dr. Shandas to see if he could take the idea and figure out how they could help patients with it. That was compelling to him. He learned a lot about GI and EoE in the process.

 

[7:30] Dr. Ackerman and Dr. Furuta started working on the string test in 2006. It took more than 16 years from concept and pre-clinical lab studies to its marketing and adoption for routine clinical use. It was officially in the clinic at the beginning of 2023.

 

[8:01] Holly Knotowicz was a clinical fellow at Children’s Hospital Colorado in 2010 where they were talking about this and she recognized this would be life-changing for patients in all populations not to have to participate in sedation to get updated information.

 

[8:32] The esophageal mucosa has biological information that may reflect the status of the disease in the esophagus. The conventional way of evaluating what is happening in the esophagus is to put a scope down the throat, pinch out a biopsy from the esophagus, and analyze that tissue for inflammatory cells and inflammatory markers.

 

[9:19] Dr. Shandas learned that the mucosa lining the esophagus has a lot of biological information. Because it is a barrier between the outside and your body it has a lot of biochemical reactions; it may be exposed to environmental allergens or food issues. These things interact with your body through the mucosal layer. It’s a complex layer.

 

[10:08] Scientists are just starting to figure out the number of things that go on in the esophageal mucosal layer. The string test samples the esophageal mucosa from the throat down to the stomach, for the entire length of the esophagus. The mucosa is the repository of information on how your body interacts with EoE.

 

[10:39] The molecules that the body releases as a function of the reaction that’s taking place are expressed in the mucosal layer. The string test collects samples of that mucosal layer. It’s a simple, non-painful, non-traditional method of sampling. 

 

[11:10] The researchers figured out there’s a lot of biological information in the mucosa. Dr. Furuta and Dr. Ackerman have both done clinical studies comparing the string test against traditional biopsies to show that there are great correlations. So they set out to develop a clinically available test.

 

[11:30] For the past eight years, EnteroTrack has done work to answer questions such as: What is the process of swallowing the device and getting the sample? What is the process of analyzing the sample? And how do we put all of that into the framework of a clinical product that can be available to patients and clinicians?

 

[11:49] The string test is a phenomenally simple, easy way to sample mucosal content and analyze it for biomarkers, with no need for any sedation or anything to help you swallow the device. It’s a very simple technique.

 

[12:32] Dr. Ackerman was a skeptic when Dr. Furuta first approached him with the idea. He agreed on the need to sample at the site of inflammation. He was surprised at how good the test was in the 16-hour overnight format, compared to endoscopy and biopsy. It was hard to tell the figures apart between the two tests.

 

[13:14] Dr. Ackerman learned they only needed to measure one eosinophil-specific biomarker, major basic protein-1, for a 16-hour test, but when they changed it to a one-hour test, they needed to measure two biomarkers to get enough of a sample. The second biomarker is eotaxin-3, which attracts the eosinophils into the esophagus.

 

[14:18] Dr. Ackerman tells of clinical validation. After multiple applications to the FDA Rare Diseases Program, they were able to get substantial funding to do a Stage 2 clinical evaluation. It was a four-year grant but it took six years to recruit all the patients. They completed and published it in 2019 as the basis for the string test and EoE score.

 

[15:03] Today, the string test is a one-hour test. The visit takes about 90 minutes, including the test, preparation, and removal of the string. The sample is sent to a reference lab. They analyze it and in about 10 days, send your doctor a report that describes the EoE score and the magnitude of the disease.

 

[16:43] There is no recommended frequency for the string test. It can be done as often as your doctor wants to keep track of changes in your disease. Until the string test, there hasn’t been a real solution to monitor the disease, with samples every week, two weeks, or four weeks. The researchers encourage patients to ask their clinicians for the string test.

 

[18:19] After setting a baseline, the frequency of tests can be determined by the patient’s progress and the clinician's findings.

 

[18:45] The string test is not a replacement for endoscopy. Endoscopy plays an important role in definitively diagnosing the disease and getting a comprehensive sense of what’s going on with the disease. The string test is a complement to endoscopy. 

 

[19:23] An endoscopic pinch biopsy samples a tiny fraction of the esophageal surface area. EoE is a patchy disease. It can manifest in different places in your esophagus. You may need to do multiple biopsies to make sure you’re covering the esophagus nicely and identify a location where the disease manifests.

 

[20:01] An advantage of the string test is that in one test, you get a sample from your throat to your stomach, the entire length of the esophagus. That allows you to get a very comprehensive evaluation of your esophagus. The ease, cost, time savings, out-patient setting, no endoscopy suite, no endoscopist, and no anesthesiologist, are advantages.

 

[20:39] EnteroTrack is pursuing the possibility of doing point-of-care in-home use of the string test. This would be a significant advantage over the traditional way of monitoring the disease.

 

[21:08] A string test cannot be used instead of an endoscopy to make the initial diagnosis of EoE. It’s intended as a monitoring tool. Its clinical indication is not as a diagnostic test but for monitoring the disease, in combination with a lab analysis of the assay. Endoscopy is used for the diagnosis.

 

[21:45] In areas where endoscopy and biopsy are not locally available, doctors might use the string test to screen patients to consider referring them to a center where they can get an endoscopy and a biopsy as an initial diagnostic tool.

 

[22:49] Holly is excited to have access to the string test for patients on elimination diets, to test more frequently as foods are reintroduced one at a time to the diet, without putting the patient under anesthesia for a traditional endoscopy.

 

[23:58] During the monitoring of EoE, if the doctor sees the data is trending in a certain way, it may be useful to get an endoscopy and biopsy to get additional information.

 

[24:28] Ryan has had dozens of traditional endoscopies and biopsies so he’s always excited to hear about new tests. He’s been putting off an endoscopy and he needs one soon. Is Ryan, an adult, a candidate for this procedure at his local hospital? Yes! He has been diagnosed with EoE, so he can be monitored by the string test.

 

[25:12] The youngest patient to swallow the device was a four-year-old and they did great with it; the test was very successful. EnteroTrack recommends that parents talk to their child’s physician about the option to use this device. The key is if the patient, parent, and clinicians all feel that the patient can swallow the device.

 

[25:35] The string test device is about the size of a TicTac®. It’s important for the swallowing procedure to be successful. EnteroTrack works with clinical groups to give them tips on how best to ensure that the procedure is successful.

 

[25:56] Holly is a feeding specialist. One of the things she helps people with eosinophilic diseases to learn is how to swallow pills. She helps them practice with different kinds of candies and capsules. 

 

[26:40] The clinical validation study included patients aged seven and older. Now that the product is released, clinicians, parents, and patients can together make the decision if they can swallow it. EnteroTrack looks at de-identified data to evaluate how the string test is doing. They are seeing younger age groups successfully swallow it.

 

[27:25] There are factors that contribute to successful swallowing. One is the parental motivation of their children. Also, practice swallowing something the size of the device.

 

[27:39] EnteroTrack is providing training to physicians and nurses at the centers that are adopting the test. They are aware of how to make the swallowing part of this test as successful as possible with the least amount of stress.

 

[28:02] The EnteroTracker® is considered a minimal-risk device, and minimal-risk procedure. If you are anxious about swallowing, or you have challenges as you swallow it, you may gag a little bit.

 

[28:37] In the Phase 2 data, there was a small percentage who had challenges in terms of gagging, when swallowing the device. All of those issues were resolved. Even if the patient gags, the clinician has tips to help the patient get through that. Repeated gulps of water can help bring the capsule down and alleviate those issues.

 

[29:37] In the clinical validation studies, there were hundreds of string tests performed and there were no serious adverse reactions or problems other than the minor problem of some gagging. During the 16-hour tests, there was one patient who chewed through the string while sleeping and swallowed it. The string just passed through the GI tract.

 

[32:47] Dr. Shandas has personally swallowed about 50 string tests to understand the patient experience. After the swallow, when the string is in the esophagus, there is a feeling of tickling in the side of the throat in the beginning, but that resolves in a couple of minutes and it is not noticed at all. It helps if the patient has something to occupy their attention.

 

[34:05] The nurses and clinicians are trained to pull the device out, not fast and not slow. It should take three to five seconds. There is some discomfort as the string is coming out. It may feel like burning in the throat but it happens quickly and it resolves immediately. They have not seen big challenges with this, much less than in swallowing.

 

[34:50] The string has two parts. The part that goes from your mouth down your throat is like dental floss. It’s connected to the collection string that goes down the esophagus to the stomach. That collection string is a thicker nylon yarn designed to optimally collect mucosal samples. It would be uncomfortable in the throat, but not in the esophagus.

 

[36:06] EnteroTrack has gotten a Medicare code for the assay and a Medicare reimbursement for the assay. The next step is getting private insurers to pay for the test. EnteroTrack is working on that. It will require educating insurance companies about the value of the test. Patients, clinicians, and groups like APFED can help.

 

[37:51] The string test is clearly less expensive than doing an endoscopy and biopsy. That should be one of the motivating factors for insurance companies. It is significantly lower cost than the test that is used as the standard of care.

 

[38:38] Some large centers have begun using the esophageal string test, including Denver, Phoenix, Tampa, Dallas, and Chicago. EnteroTrack has received interest from clinicians and patients around the country.

 

[39:04] Patients and parents, let your clinicians know if you are interested in the esophageal string test (EST). Your doctor can contact EnteroTrack and ask how to get the test to their clinic. It’s a simple process and the clinical training is very straightforward.

 

[39:35] APFED plans to add information about the esophageal string test to its Specialist Finder at apfed.org/specialist to help patients find clinicians offering this test.

 

[39:53] Drs. Ackerman and Shandas anticipate that the number of centers offering this test will grow exponentially as people see that it’s working for early adopters.

 

[40:10] Ryan and Holly thank Drs. Shandas and Ackerman for sharing their expertise to help others today in the podcast. Dr. Shandas thanks Ryan, Holly, and APFED for the opportunity to talk about the string test.

 

[40:35] As entrepreneurs and researchers, they are constantly innovating, including looking for other applications for the string test. They have clinical trials going on to use the string test for esophageal issues, gastric issues, and small intestinal issues, analyzing the contents for different biomarkers that have correlations with a lot of upper GI diseases.

 

[41:22] To learn more about eosinophilic esophagitis, visit apfed.org/eoe, to access the Specialist Finder, visit apfed.org/specialists, and to connect with patients and families living with eosinophilic disorders, visit apfed.org/eos-connections. Ryan and Holly thank Drs. Shandas and Ackerman again for an interesting conversation and thank APFED’s education partners, linked below, for supporting this episode.

 

Mentioned in This Episode:

American Partnership for Eosinophilic Disorders (APFED)

APFED on YouTube, Twitter, Facebook, Pinterest, Instagram

Dr. Robin Shandas

Dr. Steven Ackerman

EnteroTrack, LLC

Mayo Clinic

Dr. Glenn Furuta

The University of Colorado

Real Talk: Eosinophilic Diseases Podcast

 

Education Partners: This episode of APFED’s podcast is brought to you thanks to the support of AstraZeneca, Bristol Myers Squibb, Sanofi, and Regeneron.

 

Tweetables:

 

“I was interested in studying how the eosinophil participates in tissue remodeling and fibrosis of the esophagus in EoE and other eosinophil-associated diseases. Notably, this started with a small research grant from APFED in 2007 to 2008.” — Dr. Steven Ackerman

 

“The mucosa that lines your esophagus has a lot of biological information. … The mucosa is the barrier between the outside world and your body. It is this very interesting biological fluid and … it has a lot of biochemical reactions.” — Dr. Robin Shandas

 

“Since we released the product earlier this year, we’ve had a four-year-old swallow the device; did great, very successful. And so, we recommend that patients, parents, talk to your physician.” — Dr. Robin Shandas

 

Featured speakers:

Dr. Steven Ackerman

Dr. Robin Shandas