Clinical Trials Offer New Opportunities to Reshape the Future of Gastrointestinal Medicine

According to a report published by the National Institutes of Health, 2.56 million people died globally in 2019 alone due to digestive diseases.¹ That's equivalent to roughly 7200 Boeing 777 plane crashes. Alarmingly, another recent report published by the American Gastroenterological Association reveals that 40% of Americans' daily lives are disrupted by digestive disorders.² Although these numbers shed light on the scale of damage caused by digestive disorders, it is crucial to understand the role of the digestive system in the human body before exploring the significance of clinical trials and the corresponding drug discoveries made in this field.

Food is the fuel that keeps the human body going. After eating, the food and liquids travel through a series of organs in the digestive system, which is made up of the gastrointestinal (GI) tract, liver, pancreas, and gallbladder. The GI tract includes a group of organs: the mouth, throat, esophagus, stomach, small intestine, large intestine, rectum, and anus. It helps absorb nutrients and water from the food to help keep us healthy. Anything that isn't absorbed keeps moving through it until it is eliminated from the body. This system plays a vital role in the absorption and digestion of the food we eat, so any negative impact on its functioning, such as GI disorders, can create massive problems.

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The Spectrum of GI Disorders and the Role of Clinical Trials

GI disorders encompass a broad spectrum of conditions affecting the entire digestive system. From gastrointestinal cancers to inflammatory bowel diseases such as Crohn disease and ulcerative colitis, the impact of these disorders on individuals' lives is significant. This is where clinical trials play a vital role in uncovering new therapies, diagnostic tools, and preventive measures to combat a wide range of GI disorders and diseases.

According to data from ClinicalTrials.gov, the number of registered trials in GI medicine has steadily risen over the years. In 2011, there were approximately 1,500 registered trials in this field, and by 2020, that number had more than doubled to over 3,500 trials.³ From targeted therapies to microbiome transplantation, the success of clinical trials in GI medicine can be exemplified through specific breakthroughs achieved in recent years.

One notable example is a pivotal study focused on targeted therapy for ulcerative colitis (UC). UC is a chronic inflammatory bowel disease that affects the colon.⁴ It occurs when the immune system sends white blood cells into the lining of the intestines, where they cause chronic inflammation and ulcerations. It can cause significant and debilitating disruptions in daily life, impacting millions of people worldwide who live with ulcerative colitis.⁴

Breakthroughs in Ulcerative Colitis Treatment

In 2022, as a part of a Phase 3 study, Eli Lilly tested a new drug called mirikizumab (Omvoh) for the treatment of ulcerative colitis (UC).⁴ The study included 1058 patients with moderate to severe UC who were randomly assigned to receive either mirikizumab or a placebo. The results showed that mirikizumab was more effective than the placebo in reducing UC symptoms and improving other measures of the disease, such as endoscopic remission and mucosal healing. After 12 weeks of treatment, 28.2% of patients on mirikizumab achieved clinical remission, compared to 11.3% of patients on the placebo.⁴

Mirikizumab's mechanism of action centers around blocking a protein called IL-23, which plays a role in the inflammation associated with UC. By blocking IL-23, it aims to reduce inflammation and improve symptoms for patients diagnosed with UC.⁴ These promising findings offer hope for a new and potentially more effective treatment option for individuals living with UC.

Advancements in Crohn Disease Treatment

Crohn disease is another chronic GI condition where inflammation occurs in the digestive tract, leading to persistent symptoms like diarrhea and abdominal pain. It can worsen over time and sometimes requires surgery.

In a recent development, on May 18, 2023, the FDA approved upadacitinib (Rinvoq, AbbVie) as a once-daily pill for adults with moderately to severely active Crohn disease.⁵ This approval came after a successful clinical trial that examined the effectiveness and safety of upadacitinib in treating Crohn disease.⁵

Upadacitinib is a small-molecule drug that targets a protein called JAK, which is involved in inflammation. The use of upadacitinib resulted in both early and long-term relief from symptoms, as well as a visible reduction in damage to the intestinal lining caused by excessive inflammation.⁵ Although targeted therapies for chronic GI conditions are on the rise, research on the gut microbiome has also gained significant traction in recent years.

Exploring the Gut Microbiome: Fecal Microbiota Transplantation

Clinical trials investigating the gut-brain axis in GI disorders, such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), have unveiled novel treatment approaches, including fecal microbiota transplantation (FMT) and targeted modulation of the microbiota. The MicroTrans trial, initiated in 2018, looked at the use of a procedure called Fecal Microbiota Transplantation (FMT) in patients with irritable bowel syndrome (IBS).⁶ FMT involves transferring healthy gut bacteria from a donor to the patient's gut to restore a healthier balance. The trial showed promising results, with some patients experiencing symptom improvement and restoration of a healthier gut microbiome.

Similarly, the landmark Phase 3 PUNCH CD3 trial, which concluded in 2022, studied the effects of FMT on patients with Clostridioides difficile infection, a condition that causes diarrhea and colitis, revealing significant benefits in reducing disease activity.⁷ This successful clinical trial led to the launch of the first FDA-approved fecal microbiota-based medicine for patients diagnosed with this GI condition.⁷

Although the advent of targeted therapies and the exploration of the microbiome and gut-brain axis has brought hope to patients grappling with advanced GI conditions, the management of the vast amount of data generated by these clinical trials and the extraction of meaningful insights have presented a significant challenge for research organizations. Fortunately, in this era, we can turn to modern data analysis techniques and harness the power of artificial intelligence (AI) to alleviate this predicament.

Harnessing the Power of AI in Clinical Trials

The integration of big data analytics and AI algorithms allows researchers to extract valuable insights from vast amounts of patient data, leading to more precise and personalized treatments for GI conditions. For instance, machine learning algorithms can analyze patient data, genetic profiles, and treatment outcomes to identify predictive markers for response to therapy. This approach enables researchers to accurately identify patient subgroups that are more likely to benefit from specific interventions, optimizing treatment strategies and improving patient outcomes.

In addition, AI-powered image analysis has transformed the field of diagnostic imaging in GI medicine. By utilizing deep learning algorithms, researchers can analyze medical images, such as CT scans or endoscopic images, to detect and classify abnormalities with high accuracy. This technology assists in the early detection and characterization of GI lesions, enabling timely interventions and improving patient prognosis. For example, studies have shown the efficacy of AI algorithms in diagnosing and characterizing colorectal polyps during colonoscopy, reducing the need for unnecessary surgeries.⁸

Addressing the Multifaceted Challenges in AI-Enabled Clinical Trials

Although a hybrid approach that combines AI with modern methods such as targeted therapies and microbiome transplantation can significantly accelerate the course of research in GI medicines, these clinical trials still face several daunting challenges that cannot be overlooked. Although AI models have made impressive strides in predicting outcomes and processing vast amounts of data within minutes, they are not infallible. Concerns persist regarding the lack of diversity in data, inherent biases, ethical considerations, privacy issues, as well as the precision and accuracy of these models, which necessitate ongoing research and improvement.

Operationally, conducting successful clinical trials poses additional hurdles. Ensuring adequate enrollment numbers for each study and at multiple sites, adhering strictly to protocols, and maintaining the necessary financial resources to sustain these complex trials are among the challenges faced by clinical research organizations in today's dynamic landscape. Overcoming these obstacles is crucial to advancing GI medicine and realizing the full potential of AI-driven approaches in transforming patient care and outcomes.

The landscape of clinical trials in digestive health is undergoing a rapid evolution, propelled by advancements in research and the integration of modern techniques such as AI-enabled image analytics, targeted therapies, and fecal microbiota transplantation. These innovations are revolutionizing diagnostics and optimizing treatment outcomes, marking significant strides in our fight against digestive diseases. However, we must confront a sobering reality: these diseases claim 2.56 million lives globally each year,¹ equivalent to the entire population of Chicago disappearing annually.

These figures are not mere statistics, but poignant reminders of the human lives at stake—each representing a person with dreams and aspirations and a family left in mourning. It underscores the urgency of researchers’ work, reminding us that our mission extends beyond advancing medical science; it's about safeguarding the human spirit. As we continue to innovate and push boundaries, we must ask ourselves: Are we moving swiftly enough to counteract the silent epidemic of digestive diseases, or are we merely addressing symptoms of a system in need of a more profound, holistic healing touch?

About the Author

Deepika Khedekar is a Clinical Trial Lead at IQVIA Inc, a global clinical research organization where she spearheads clinical trial monitoring programs for major pharmaceutical companies. In her more than 12 years in the pharmaceutical industry, she led phase 1, 2,and 3 clinical trial programs in respiratory and gastrointestinal therapeutics and drugs for leading US and Australia-based pharmaceutical organizations, such as Gilead Sciences, Macleods Pharma, Arrowhead Pharmaceuticals, NoNO Inc., EpimAb, and Impact Pharma. She started her journey in the field of pharmaceutical research at Pfizer and holds a master’s degree in pharmacy from the University of Mumbai.

References

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2. New survey finds forty percent of Americans’ daily lives are disrupted by digestive troubles. News release. American Gastroenterological Association. September 14, 2022. Accessed August 7, 2023. https://gastro.org/press-releases/new-survey-finds-forty-percent-of-americans-daily-lives-are-disrupted-by-digestive-troubles/
3. National Library of Medicine Center for Biotechnology Information. Accessed August 7, 2023. https://clinicaltrials.gov/search?cond=Gastrointestinal%20diseases&start=2011-01-01_2011-12-31
4. Fifty Percent of Patients with Ulcerative Colitis Treated with Mirikizumab Achieved Clinical Remission at One Year in Lilly's Pivotal Phase 3 Study. News release. Eli Lilly. May 24, 2022. Accessed August 7, 2023. https://investor.lilly.com/news-releases/news-release-details/fifty-percent-patients-ulcerative-colitis-treated-mirikizumab
5. FDA approves first oral treatment for moderately to severely active Crohn’s disease. News release. FDA. May 18, 2023. Accessed August 7, 2023. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-oral-treatment-moderately-severely-active-crohns-disease
6. Bhide A, Datar S. Fecal Microbiota Transplants (FMT): Case Histories of Significant MedicalAdvances. Harvard Business School Working Paper. 2021. Accessed August 7, 2023. https://www.hbs.edu/ris/Publication%20Files/21-132_dc777c76-0325-4d4e-996b-a429420c7fe3.pdf
7. FDA Approves First Fecal Microbiota Product. News release. FDA. November 30, 2022. Accessed August 7, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-fecal-microbiota-product
8. Wang A, Mo J, Zhong C, Wu S, Wei S, et al. Artificial intelligence-assisted detection and classification of colorectal polyps under colonoscopy: a systematic review and meta-analysis. Ann Transl Med. 2021;9(22):1662. doi:10.21037/atm-21-5081