NASH/MASH, Liver Disease & Functional GI Disorders
A comprehensive analysis of the gastroenterology clinical trial landscape — from non-invasive fibrosis assessment and liver biopsy infrastructure to patient stratification strategies and pipeline dynamics across MASH therapeutics, functional GI treatments, and hepatology programs.
The Gastroenterology Trial Landscape in 2026
Gastroenterology clinical development is undergoing a transformative period driven by the MASH therapeutic revolution, advances in non-invasive diagnostics, and a growing pipeline of agents targeting the gut-brain axis and hepatic fibrosis pathways. Within the Clinitiative network, gastroenterology encompasses 16 active studies spanning metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), celiac disease, chronic liver disease, and functional gastrointestinal disorders. Notably, inflammatory bowel disease — including Crohn's disease and ulcerative colitis — is covered under our Immunology therapeutic spotlight, reflecting the immunological mechanisms that define IBD pathogenesis and treatment.
MASH is the dominant driver of gastroenterology trial volume, accounting for 8 of the 16 active protocols. The landmark approval of resmetirom in 2024 validated the MASH therapeutic space and catalyzed a new wave of clinical programs targeting complementary and combination mechanisms of action. The remaining portfolio is distributed across GERD (3 studies), IBS (2 studies), celiac disease (2 studies), and functional dyspepsia (1 study). This distribution reflects the dual nature of gastroenterology clinical research — hepatology programs that require intensive diagnostic infrastructure and long treatment durations, alongside functional GI programs that demand large patient volumes and sophisticated placebo management strategies.
The gastroenterology landscape is being reshaped by two parallel developments: the rapid adoption of non-invasive biomarkers as alternatives to liver biopsy in MASH trials, and the emergence of microbiome-based therapeutics and gut-brain axis modulators for functional GI disorders. Non-invasive technologies including vibration-controlled transient elastography (FibroScan/VCTE), magnetic resonance imaging proton density fat fraction (MRI-PDFF), and the Enhanced Liver Fibrosis (ELF) panel are increasingly being incorporated as both screening tools and efficacy endpoints, reducing the biopsy burden that has historically been the greatest barrier to patient enrollment in hepatology trials.
Key Performance Metrics
Network-wide benchmarks from our gastroenterology portfolio provide critical reference points for study planning and site performance evaluation across hepatology and functional GI indications.
Enrollment rates in gastroenterology vary substantially by indication and diagnostic complexity. MASH studies average 1.2 patients per site per month, constrained by the multi-step screening process that includes non-invasive fibrosis assessment, histologic confirmation via liver biopsy, and NAS score verification. IBS studies achieve significantly higher enrollment at 2.4 patients per site per month, benefiting from high disease prevalence and symptom-based diagnostic criteria that streamline the screening process. GERD studies fall between these extremes at 1.8 per site per month.
The gastroenterology portfolio carries one of the highest screen failure rates in our network, driven primarily by the stringent histologic and staging requirements in MASH programs. Liver biopsy-based screening in MASH studies produces screen failure rates of 50-60% when fibrosis stage confirmation (typically F2-F3) and minimum NAS scores are required. IBS studies contribute lower screen failure rates at 25-30%, while GERD programs requiring endoscopic confirmation of erosive disease average 35%. The aggregate 42% rate reflects the MASH-weighted composition of the current portfolio.
Gastroenterology site startup timelines are extended by the specialized infrastructure requirements of hepatology programs. Sites conducting MASH studies require established liver biopsy capabilities, interventional radiology partnerships, pathology review workflows with NAS-trained hepatopathologists, and FibroScan or equivalent non-invasive assessment equipment. These requirements extend the qualification and setup process by 4-6 weeks compared to functional GI programs. Sites with pre-existing hepatology research infrastructure achieve startup at 12.5 weeks, while sites requiring de novo capability development average 18-20 weeks.
Patient retention in gastroenterology studies reflects the divergent dynamics of hepatology and functional GI programs. MASH studies, which typically require 48-72 weeks of treatment to assess fibrosis regression endpoints, experience gradual attrition over time with retention rates of 74-76%, driven by the asymptomatic nature of early-stage disease and patient fatigue with long study durations. IBS studies show paradoxically lower retention at 72-75% despite shorter durations, as high placebo response rates lead to patient re-assessment of study participation. GERD studies maintain the highest retention at 85% due to clear symptomatic benefit assessment.
Network Capabilities
Executing gastroenterology trials across both hepatology and functional GI indications requires a diverse set of specialized capabilities that span invasive procedures, advanced imaging, motility testing, and endoscopic infrastructure. Our network has been developed to provide comprehensive gastroenterology research support across this full spectrum of requirements.
Hepatology & Liver Biopsy Infrastructure
Liver biopsy remains the reference standard for MASH diagnosis and staging despite the growing role of non-invasive alternatives. Our network sites maintain established liver biopsy programs with board-certified interventional radiologists or hepatologists performing percutaneous biopsies under ultrasound guidance. Dedicated post-procedure observation areas ensure patient safety during the required 4-6 hour monitoring period. Biopsy specimens are processed according to sponsor-specific protocols and reviewed by hepatopathologists trained in the Brunt classification system and NASH Clinical Research Network (CRN) NAS scoring methodology. Sites with established biopsy programs achieve biopsy adequacy rates exceeding 92%, ensuring that sufficient tissue length and portal tract counts are obtained for reliable histologic assessment.
For studies requiring paired biopsies — a baseline biopsy for enrollment confirmation and an end-of-treatment biopsy for efficacy assessment — our sites implement patient engagement strategies that address the anxiety and reluctance associated with repeat invasive procedures. These include detailed patient education about the biopsy process, conscious sedation options, and follow-up care protocols that build patient confidence and willingness to complete the second biopsy.
Non-Invasive Fibrosis Assessment
The gastroenterology field is rapidly transitioning toward non-invasive assessment technologies that reduce patient burden and enable broader screening. Our network sites are equipped with FibroScan (vibration-controlled transient elastography / VCTE) devices with both M and XL probes to accommodate varying body habitus, enabling reliable liver stiffness measurement across the full range of MASH patients including those with elevated BMI. MRI-PDFF capabilities are available for studies requiring quantitative hepatic fat fraction measurement, with standardized acquisition protocols that ensure cross-site consistency and central imaging vendor compatibility.
Serum-based fibrosis panels including the ELF test, FIB-4 index, and NAFLD Fibrosis Score are integrated into standard screening workflows, enabling efficient patient pre-selection before proceeding to more costly imaging or biopsy assessments. Sites utilizing a tiered screening approach — serum biomarkers followed by FibroScan followed by biopsy — achieve 25% lower overall screening costs compared to sites that proceed directly to biopsy-based confirmation.
GI Motility & Function Testing
Functional GI disorder studies frequently require specialized motility and function testing as part of screening, baseline characterization, or pharmacodynamic assessment. Our network sites maintain GI motility laboratories equipped for high-resolution esophageal manometry, anorectal manometry, pH impedance monitoring (both catheter-based and wireless Bravo systems), hydrogen and methane breath testing for small intestinal bacterial overgrowth (SIBO) and carbohydrate malabsorption, and SmartPill wireless motility capsule studies for whole-gut transit assessment.
These capabilities enable precise phenotyping of functional GI patients, supporting biomarker-stratified enrollment strategies that are increasingly common in IBS and functional dyspepsia protocols. Sites with comprehensive motility capabilities can efficiently characterize patient populations and reduce screen failure rates by identifying eligible patients through objective physiologic measurements rather than relying solely on symptom-based criteria.
Endoscopy & Procedure Capabilities
Endoscopic capabilities are essential across multiple gastroenterology indications, from GERD studies requiring esophagogastroduodenoscopy (EGD) for erosive esophagitis grading to celiac disease programs requiring duodenal biopsy for villous atrophy assessment. Our network sites maintain fully equipped endoscopy suites with upper and lower endoscopy capability, capsule endoscopy for small bowel evaluation, and endoscopic biopsy infrastructure with standardized specimen processing protocols. All endoscopy procedures are performed by board-certified gastroenterologists with research experience, ensuring consistent grading of endoscopic findings using validated classification systems such as the Los Angeles classification for esophagitis and the Marsh classification for celiac disease histopathology.
Enrollment Dynamics
Gastroenterology enrollment dynamics vary dramatically between hepatology programs, which face the challenge of identifying and confirming patients with specific histologic disease stages, and functional GI programs, which benefit from large patient pools but contend with high placebo response rates and subjective diagnostic criteria. Understanding these distinct dynamics is essential for realistic enrollment planning across the gastroenterology portfolio.
MASH patient identification represents the most complex enrollment challenge in gastroenterology. The majority of MASH patients are undiagnosed, as the disease is largely asymptomatic until advanced stages. Our network leverages electronic health record (EHR) screening algorithms that identify patients with metabolic syndrome features — elevated ALT, obesity, type 2 diabetes, and dyslipidemia — who have a high probability of underlying MASH. This proactive identification approach increases the pre-screening pipeline by 3-4x compared to passive referral-based recruitment. However, the conversion from EHR-identified candidates to enrolled patients remains challenging, as many identified patients have never been informed of their liver disease and require education and counseling before they are willing to participate in clinical research involving liver biopsy.
IBS recruitment benefits from the enormous prevalence of the condition, estimated at 10-15% of the global adult population, but faces unique challenges related to patient self-selection and diagnostic confirmation. Many IBS patients manage their symptoms independently and may not seek medical care, requiring outreach through primary care networks, digital advertising, and community engagement to build awareness of available clinical trials. Once identified, patients must meet Rome IV diagnostic criteria and complete run-in diary periods that confirm symptom severity and frequency thresholds, which introduces an additional screening attrition layer.
Patient reluctance for repeat invasive procedures — particularly liver biopsies in MASH studies and endoscopies in GERD and celiac programs — remains a significant retention risk throughout the study lifecycle. Our network addresses this through clear communication of procedure expectations at the informed consent stage, patient support programs that provide dedicated coordinator contact for procedure-related concerns, and scheduling flexibility that accommodates patient preferences for procedure timing and recovery support.
Key Challenges in Gastroenterology Trial Execution
The diagnostic complexity of hepatology programs and the subjective nature of functional GI endpoints present operational challenges that require specialized strategies and infrastructure.
Liver Biopsy Burden & Patient Reluctance
Paired liver biopsies remain the regulatory gold standard for demonstrating histologic improvement in MASH trials, but they represent the single greatest barrier to patient enrollment and retention. Patients who are willing to undergo a screening biopsy may decline the end-of-treatment biopsy, particularly if they feel well and perceive no symptomatic benefit from study participation. Our network data shows that biopsy-related dropout accounts for 15-20% of all discontinuations in MASH studies. Mitigation strategies include detailed pre-enrollment counseling that sets clear expectations for paired biopsies, conscious sedation protocols that minimize procedure-related anxiety, same-day biopsy scheduling to reduce patient time burden, and dedicated biopsy coordinator roles that provide personalized patient support throughout the procedure process.
MASH Heterogeneity & Staging
MASH is a histologically defined disease with significant sampling variability that introduces uncertainty into both enrollment and efficacy assessment. The NAFLD Activity Score (NAS) combines scores for steatosis, lobular inflammation, and hepatocyte ballooning, but inter-observer agreement among pathologists, even trained hepatopathologists, is imperfect. Fibrosis staging using the Brunt or NASH CRN system similarly shows inter-reader variability, particularly at the critical F2-F3 boundary that defines most current trial eligibility criteria. Our network addresses this through centralized pathology review with dual-read adjudication, standardized biopsy processing protocols that ensure adequate specimen quality, and pre-screening non-invasive assessment to enrich the biopsy population for patients most likely to meet histologic eligibility criteria.
Placebo Response in Functional GI
Functional GI disorders — particularly IBS and functional dyspepsia — consistently demonstrate placebo response rates of 30-40% in randomized controlled trials, representing a fundamental challenge to demonstrating treatment efficacy. The high placebo response is driven by multiple factors including the natural symptom fluctuation of these conditions, the therapeutic effect of regular medical attention and symptom monitoring during study participation, and regression to the mean in patients enrolled during symptom flares. Our network implements evidence-based placebo response mitigation strategies including extended run-in periods with diary confirmation of symptom persistence, baseline severity enrichment criteria, validated symptom scoring instruments with demonstrated sensitivity to change, and patient education that emphasizes the importance of accurate symptom reporting regardless of perceived treatment assignment.
Long Study Durations in Hepatology
MASH clinical trials targeting fibrosis regression endpoints require treatment durations of 48-72 weeks, and some cirrhosis outcomes studies extend to 3-5 years. These extended timelines create compounding retention risks including patient fatigue with visit schedules, relocation, changes in health status, loss of motivation in an asymptomatic condition, and competing clinical trial opportunities. Our network maintains patient engagement through flexible visit scheduling, telehealth check-ins between required in-person visits where protocol-permitted, patient milestone recognition programs, and coordinator continuity that ensures patients maintain a consistent relationship with their primary study contact throughout the extended treatment period. Sites with established long-duration study experience achieve 8-12% higher retention rates compared to sites new to hepatology research.
Pipeline Analysis
The gastroenterology development pipeline is experiencing unprecedented growth, led by the MASH therapeutic space but extending across functional GI disorders, celiac disease, and advanced hepatology programs. Several key therapeutic trends are reshaping trial design, endpoint selection, and site requirements across the field.
MASH Therapeutics
The MASH therapeutic pipeline has expanded dramatically following the approval of resmetirom, with multiple mechanisms of action advancing through Phase II and Phase III development. Farnesoid X receptor (FXR) agonists continue to progress with refined molecules designed to improve the tolerability limitations of first-generation compounds. Thyroid hormone receptor beta (THR-beta) agonists in the resmetirom class represent the current leading mechanism, with several follow-on compounds in development. GLP-1 receptor agonists, validated by the metabolic benefits observed with semaglutide and tirzepatide in MASH populations, are entering dedicated MASH programs with histologic endpoints. FGF21 analogs target the metabolic root causes of steatohepatitis with promising early-phase data on liver fat reduction and fibrosis improvement. Combination approaches pairing agents from different mechanism classes represent the next frontier, requiring sites capable of managing complex multi-drug protocols with layered safety monitoring requirements.
Novel IBS & Functional GI Therapies
The functional GI pipeline is evolving beyond traditional motility and secretion-based mechanisms toward therapies that target the gut-brain axis, the intestinal microbiome, and bile acid signaling pathways. Gut-brain axis modulators — including peripheral kappa-opioid agonists, visceral pain-targeted agents, and centrally acting neuromodulators with improved side effect profiles — are advancing through clinical development for IBS with predominant abdominal pain. Microbiome-based therapeutics, including defined microbial consortia and engineered probiotics, are being evaluated for IBS subtypes where dysbiosis has been implicated in pathogenesis. Bile acid modulators targeting FXR and TGR5 receptors are being studied for IBS with predominant diarrhea (IBS-D), where bile acid malabsorption contributes to symptom severity in a significant patient subset.
Celiac Disease Pipeline
Celiac disease, which currently has no approved pharmacologic treatment beyond dietary gluten avoidance, is attracting significant pipeline investment across multiple therapeutic mechanisms. Gluten-degrading enzymes aim to provide protection against inadvertent gluten exposure by breaking down immunogenic gluten peptides in the GI tract before they can trigger an immune response. Tight junction modulators target the intestinal permeability that allows gluten peptides to access the lamina propria and activate the adaptive immune response. Tissue transglutaminase 2 (TG2) inhibitors block the enzymatic deamidation of gluten peptides that enhances their immunogenicity and drives the celiac inflammatory cascade. These programs require sites with expertise in celiac disease assessment, duodenal biopsy capability for villous atrophy grading, serologic monitoring of tissue transglutaminase antibodies, and gluten challenge protocols that standardize disease provocation in controlled settings.
Advanced Hepatology Programs
Beyond MASH, the hepatology pipeline encompasses anti-fibrotic agents targeting advanced liver fibrosis and compensated cirrhosis, combination therapeutic approaches that pair anti-inflammatory and anti-fibrotic mechanisms, and hepatocellular carcinoma (HCC) chemoprevention strategies for patients with established cirrhosis who are at high risk for malignant transformation. These advanced hepatology programs present the most demanding site requirements in gastroenterology, including expertise in managing patients with advanced liver disease, MELD score monitoring, portal hypertension assessment, hepatic decompensation event adjudication, and coordination with hepatology transplant programs for patients who may require liver transplantation during the study period. Sites with established hepatology research programs and close integration with academic liver transplant centers are preferentially positioned for these complex, high-stakes clinical programs.
Site Requirements for Gastroenterology Excellence
The infrastructure, staffing, and operational processes required to execute modern gastroenterology protocols at the highest level of quality across hepatology and functional GI indications.
Ultrasound-guided percutaneous liver biopsy capability with interventional radiology or hepatologist operators, dedicated post-procedure observation areas with minimum 4-hour monitoring capacity, standardized specimen processing for NAS scoring, and established hepatopathology review partnerships with dual-read adjudication capability.
FibroScan (VCTE) with M and XL probes for liver stiffness measurement across all BMI ranges, MRI capability with PDFF acquisition protocols for hepatic fat quantification, standardized imaging protocols compatible with central imaging vendor requirements, and trained operators with quality metrics monitoring for FibroScan reliability.
High-resolution manometry (esophageal and anorectal), pH impedance monitoring with catheter and wireless options, hydrogen and methane breath testing for SIBO and carbohydrate malabsorption assessment, SmartPill wireless motility capsule capability, and trained GI physiology technicians with standardized reporting protocols.
Fully equipped endoscopy suite with upper and lower endoscopy capability, capsule endoscopy for small bowel evaluation, endoscopic biopsy with standardized specimen processing, conscious sedation and recovery infrastructure, and board-certified gastroenterologist endoscopists with research protocol experience and validated scoring expertise.
Research pharmacy with temperature-controlled storage for investigational products, oral formulation dispensing with adherence monitoring systems, drug accountability documentation, and capability to manage complex multi-drug combination protocols. Specialized handling for microbiome-based investigational products requiring specific storage conditions.
Board-certified gastroenterologist and hepatologist investigators with clinical trial experience, GI-trained clinical research coordinators with expertise in biopsy coordination and motility testing, data managers proficient in hepatology-specific EDC systems, and regulatory coordinators managing IRB submissions for procedures involving invasive diagnostics and long-duration protocols.
Discuss Your Gastroenterology Program
Connect with our team to explore site capabilities, enrollment strategies, and hepatology infrastructure for your gastroenterology clinical development program.