Celiac Disease Clinical Trials: Modern Treatments, Study Designs, and How to Take Part

Introduction

Clinical research is reshaping the outlook for people living with celiac disease. While a lifelong gluten free diet remains the only approved treatment, a growing wave of celiac disease clinical trials is testing drugs, immunotherapies, and support tools that could change the way this condition is managed. This guide walks through the science behind those trials, the patients they serve, what participation actually looks like, and how to decide whether a study might be right for you.

Fast facts for people considering a celiac disease clinical trial

Clinical trials are carefully regulated research studies that evaluate whether a new drug, therapy, or medical approach is safe and effective before it becomes available to the public. For celiac disease, these studies matter because the only treatment currently approved is a strict gluten free diet, and many patients continue to experience abdominal pain, fatigue, diarrhea, or ongoing intestinal damage even when they follow that diet closely.

Here are several concrete reasons people choose to participate:

• Access to specialty care from gastroenterologists and immunologists at no cost
• Advanced diagnostics, including endoscopy, duodenal biopsies, blood biomarkers, and genetic testing
• Close symptom monitoring with regular check-ins throughout the study
• Potential access to investigational therapies months or years before FDA approval
• Financial compensation in many studies, often structured per completed visit

Advanced Research Institute (ARI) runs FDA-regulated clinical trials for celiac disease and related conditions at sites in Utah and Nevada, with plans to expand into additional regions. Celiac disease patients and referring physicians can contact ARI directly to learn about clinical research opportunities in Utah and Nevada to learn about open and upcoming studies.

It is important to understand that trial medications are experimental and may be compared to a placebo in double blind designs, meaning neither the participant nor the study team knows who receives the active drug until the study ends.

What is celiac disease and why do we need new treatments?

Celiac diseaseis an immune-mediated enteropathy of the small intestine triggered by gluten, a protein found in wheat, barley, and rye. In genetically susceptible individuals, usually those carrying the HLA-DQ2.5 or HLA-DQ8 gene variants, gluten exposure activates an immune response that damages the intestinal lining. This leads to villous atrophy, crypt hyperplasia, and malabsorption of nutrients.

Symptoms range widely and can include abdominal pain, diarrhea, bloating, weight loss, anemia, and chronic fatigue. Celiac disease affects approximately 1% of adults globally, though many cases remain undiagnosed or misdiagnosed because symptoms can mimic other conditions.

A strict gluten free diet usually allows mucosal healing and symptom relief, but it is not a cure. Hidden gluten in processed foods, cross-contamination during eating out, and the social and financial burden of dietary restrictions make perfect adherence extremely difficult. Some celiac patients suffer from persistent symptoms or incomplete healing despite verified diet compliance.

Recent clinical trials emphasize targeted disease-altering interventions for celiac disease, reflecting a growing consensus that the field needs pharmacologic therapies. Current clinical trials evaluate non-dietary therapies to prevent gut damage from gluten exposure, protect against accidental gluten exposure, and support patients whose disease does not respond to diet alone.

Types of celiac disease patients who may be eligible for trials

Different studies target different celiac disease patient groups, and understanding which category applies to you is the first step toward finding a match.

Patients in remission on a gluten free diet. These individuals have achieved histologic healing or near-healing, with negative or low celiac serology and good symptom control. They typically enter prevention trials designed to test whether a drug can block damage from accidental gluten exposure. The Ritlecitinib Phase 2 trial enrolls adult patients in this category, exposing them to a controlled gluten challenge while on active drug or placebo.

Non responsive celiac disease patients. These are symptomatic celiac disease patients who continue to have villous atrophy, abnormal labs, or persistent symptoms after at least 6 to 12 months on a verified gluten free diet. The Phase 2 ASPIRION trial of Amlitelimab is specifically designed for this population, testing whether targeted immune modulation can calm ongoing inflammation.

Newly diagnosed adults. Some early-phase or observational studies enroll patients within a few months of a biopsy-confirmed diagnosis to track mucosal recovery under guided dietary management or to evaluate support tools like telemedicine and at-home gluten detection.

Immune tolerance candidates. Patients with confirmed celiac disease who are HLA-DQ2.5 or DQ8 positive, usually on a gluten free diet for 12 or more months, may qualify for tolerance-inducing therapies like KAN-101 or VTP-1000.

ARI typically works with biopsy confirmed celiac disease patients and can pre-screen based on age, disease duration, and current symptom pattern for ongoing clinical studies in multiple locations.

How celiac disease clinical trials are designed

Randomized controlled trials remain the gold standard for evaluating new celiac therapies. In a randomized study, participants are assigned by chance to receive either the investigational drug or a placebo, reducing bias and strengthening the reliability of results.

Two key trial designs dominate current celiac disease research:

• Gluten challenge trials enroll patients on a stable gluten free diet and expose them to measured amounts of gluten to provoke immune activation and histologic damage. The protective capacity of the study drug is then assessed by comparing outcomes between the treatment and placebo groups.
• Reversal trials aim to heal existing mucosal damage in patients with non responsive celiac disease, without deliberately introducing additional gluten. Patients remain on their gluten free diet while receiving the investigational therapy.

Many celiac disease clinical trials are double blind and placebo controlled. In April 2022, the FDA released draft guidance for celiac disease drug development, aiming to standardize trial designs, define appropriate endpoints, and set expectations for inclusion criteria and outcome measures. A parallel effort using a modified Research and Development/UCLA Appropriateness Method (RAM) brought together international experts in the 2020s to refine gluten challenge protocols and endpoint definitions. The FDA’s guidance aims to standardize trial designs for celiac disease across the industry.

ARI follows these evolving best-practice guidelines when participating in multicenter studies sponsored by pharmaceutical companies or academic groups, and its clinical trial FAQs further explain how safety, oversight, and study procedures are handled.

Gluten challenge in celiac disease research

A gluten challenge is a controlled period during which patients with celiac disease consume a measured dose of gluten while under close medical supervision. Clinical trials for celiac disease often include gluten challenges because this controlled exposure provokes measurable symptoms, immune activation, and small bowel damage, providing a clear window to evaluate whether a study drug offers protection.

A gluten challenge study tests if investigational drugs prevent reactions to small gluten amounts. Concrete examples from current studies include:

• The Ritlecitinib trial uses a 21-day gluten challenge at approximately 10 grams of gluten per day
• The VTP-1000 AVALON study includes a gluten challenge after multiple ascending doses to assess immune tolerance
• Some TEV-53408 protocols use extended gluten exposure windows, with participants monitored for up to 86 weeks total

An expert panel rated a maximum gluten dose of 9 grams as appropriate for challenge protocols, though some trials use slightly higher or lower amounts depending on design objectives.

To reduce confounding from other dietary triggers, experts now recommend that a gluten challenge should be FODMAP-free in clinical trials, using specially formulated products that isolate gluten-specific reactions from broader food sensitivities.

Not all trials require a gluten challenge. Studies targeting non responsive celiac disease, such as the ASPIRION trial, keep patients on their gluten free diet and measure healing without deliberate gluten exposure.

Inclusion and exclusion criteria for celiac clinical trials

Every clinical trial has detailed inclusion and exclusion criteria to protect patient safety and produce reliable data. Here is what typical celiac trials require:

Common inclusion criteria:

• Adults aged 18 to 75 (participants must be 18–75 years old for the Ritlecitinib trial, for example)
• Biopsy confirmed celiac disease with documented histologic findings
• At least 6 to 12 months on a gluten free diet; participants in many studies must adhere to a gluten-free diet for 12 months before enrollment
• Specific villus height to crypt depth ratio thresholds, depending on whether the trial targets remission or active disease
• HLA-DQ2.5 or DQ8 genotype confirmation for certain immunotherapy studies

Common exclusion criteria:

• Age outside the specified range
• Absence of endoscopic confirmation of celiac disease
• Recent major surgery or active cancer
• Additional autoimmune diseases or inflammatory bowel disease
• Current use of immunosuppressive medications that could interfere with immune response assessment
• Severe, uncontrolled abdominal pain, anemia, or nutritional deficiencies until these are medically stabilized

ARI’s team reviews each person’s medical history, pathology reports, and lab results to determine if they meet a specific study’s criteria before scheduling any screening visits.

What happens during a celiac disease clinical trial visit

The structure of a trial visit varies by protocol, but the Phase 2 Ritlecitinib trial at Massachusetts General Hospital provides a useful model. That study involves approximately 7 visits over about 15 weeks, combining screening, baseline assessments, the treatment and gluten challenge period, and follow-up.

Common procedures across celiac trials include:

• Medical history review and physical examination
• Blood draws for celiac antibodies (tissue transglutaminase IgA, endomysial antibodies, deamidated gliadin peptides) and exploratory biomarkers
• Urine and stool collection, sometimes for gluten peptide detection to verify diet adherence
• Genetic testing (HLA genotype) and COVID-19 screening when required
• Electrocardiogram for cardiac safety monitoring

Participants in many trials undergo at least two endoscopies with duodenal biopsies, one at baseline and one after the treatment or gluten challenge period, to assess villous atrophy, intraepithelial lymphocyte density, and mucosal healing.

During the treatment window, celiac patients usually take oral capsules (active drug or placebo) each day and track gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, and bloating using symptom diaries or mobile apps. Some biologics, like TEV-53408, are administered subcutaneously rather than orally.

All study-related visits and procedures are provided at no cost to disease patients. ARI coordinates scheduling, reminders, and any required pre-procedure instructions to minimize disruption to daily life, and its clinical trial company overview highlights this participant-centered approach.

Clinical endpoints: how researchers measure success

Celiac disease clinical trials combine objective measures and patient reported outcomes to evaluate treatment efficacy. Histologic outcomes are primary endpoints in celiac disease trials, and they typically include:

Endpoint Category	Examples	When Used
Histologic	Villus height to crypt depth ratio, Marsh classification, intraepithelial lymphocyte count	Prevention and reversal trials
Endoscopic	Mucosal scalloping, nodularity	Supportive; debated frequency
Serologic	Tissue transglutaminase IgA, endomysial antibodies	Non-invasive monitoring
Immune/Biomarker	T-cell responses to gluten peptides, cytokine profiles, microbiome changes	Phase 1 immunotherapy studies
Patient-reported	Abdominal pain frequency, diarrhea severity, fatigue, overall quality of life	All phases
There are ongoing trials to better track intestinal healing and disease activity for celiac disease, incorporating newer technologies like transcriptomic profiling and single-cell RNA sequencing alongside traditional biopsy assessment. Histological assessment has a 10% diagnostic error rate in celiac disease, which has driven efforts to improve consistency through centralized pathology review and digital scoring.

Expert guidelines continue to debate how frequently follow-up endoscopy is necessary, balancing the clinical value of biopsy data against patient burden and procedural risk.

Examples of modern celiac disease clinical trials

Over 20 companies are advancing nearly 30 investigational therapies through clinical trials for celiac disease. Here are several that illustrate different therapeutic strategies:

ASPIRION: Amlitelimab for non responsive celiac disease. The ASPIRION study is evaluating Amlitelimab for nonresponsive celiac disease. Amlitelimab targets nonresponsive celiac disease patients who remain symptomatic despite a strict gluten free diet. This Phase 2a/b, randomized, double blind, placebo controlled trial tests whether the drug can improve intestinal healing and reduce the impact of accidental gluten exposure. Trial sites span multiple countries.

Ritlecitinib for gluten-induced enteropathy prevention. The Ritlecitinib trial aims to prevent gluten reactions in celiac patients who are in remission. A JAK3/TEC family kinase inhibitor, Ritlecitinib may prevent gluten reactions in celiac patients by blocking IL-15-mediated immune activation. The study uses a 21-day gluten challenge, double blind design, and enrolls approximately 62 participants. The main goal is to determine whether the drug prevents gluten induced enteropathy and symptoms measured by change in villus height to crypt depth ratio.

VTP-1000: nanoparticle immunotherapy for gluten tolerance. VTP-1000 is a first-in-human trial for gluten tolerance. Developed by Barinthus Biotherapeutics under the AVALON study name, VTP-1000 aims to build gluten tolerance in celiac patients by combining 12 gluten derived peptides with rapamycin in nanoparticles to promote regulatory T-cell responses. The single ascending dose portion is complete with no serious adverse events and dose-dependent pharmacologic effects. The multiple ascending dose portion with gluten challenge is ongoing, with data expected in the second half of 2026.

TEV-53408: anti-IL-15 antibody with Fast Track status. TEV-53408 received Fast Track designation from the U.S. FDA in May 2025. Investigational anti-IL-15 antibodies aim to lower gut inflammation in celiac disease patients by dampening inflammatory pathways that drive villous atrophy during gluten exposure. This Phase 2a trial enrolls approximately 48 to 50 adult patients aged 18 to 64, uses subcutaneous administration, and measures attenuation of gluten induced enteropathy by change in villus height to crypt depth ratio at week 8. The TEV-53408 trial monitors participants for up to 86 weeks to assess long-term safety.

GF-NOURISH: a non-drug support study. Not all celiac disease research involves medications. The GF-NOURISH study focuses on reducing ultra-processed gluten-free foods and helping newly diagnosed celiac patients improve diet quality and adherence through education, telemedicine, and at-home gluten detection tools. Studies like this evaluate how practical support affects mucosal recovery and quality of life.

Non responsive and refractory celiac disease in research

Non responsive celiac disease is defined as persistent symptoms, abnormal labs, or ongoing villous atrophy after at least 6 to 12 months on a strict gluten free diet. Truly refractory celiac disease goes further: intestinal damage persists despite verified diet adherence and after other causes, such as infection, medication side effects, or a concurrent medical condition, have been ruled out. Refractory disease is rare but carries significant risk of complications.

This group is a priority for celiac disease research because patients with celiac disease who do not respond to diet alone face impaired quality of life, higher complication rates, and no approved pharmacologic treatment. The ASPIRION Amlitelimab trial specifically enrolls non responsive celiac disease patients to test whether targeted immune modulation can calm ongoing inflammation and promote mucosal healing while patients remain on a gluten free diet.

Trials in this space often require careful dietitian assessment and may use stool or urine gluten peptide detection to confirm that symptoms are not due to ongoing gluten ingestion rather than true treatment failure.

ARI can collaborate with referring gastroenterologists to evaluate non responsive celiac disease patients for potential study participation and to share relevant test results, streamlining the eligibility determination process, consistent with its company background and mission.

Patient-reported outcomes and quality of life measures

Regulatory agencies increasingly expect celiac disease clinical trials to capture the patient experience alongside biopsy data. The FDA emphasizes patient reported outcomes in celiac disease trials as essential tools for evaluating treatment efficacy. Patient-reported outcomes are essential in evaluating treatment efficacy because histologic improvement does not always correlate with how patients feel day to day.

Common symptom domains captured by celiac PRO instruments include:

• Abdominal pain frequency and severity
• Bowel habits, including diarrhea and constipation
• Bloating and nausea
• Extra-intestinal symptoms such as headache and fatigue
• Day-to-day functioning, including ability to work and socialize

Health-related quality of life metrics also assess social limitations, anxiety about accidental gluten exposure, and the financial and emotional burden of maintaining a gluten free diet. Expert panels have developed specific recommendations for both adult and pediatric PRO measures to improve consistency between studies.

ARI staff help participants complete diaries and questionnaires accurately, emphasizing that honest symptom reporting, even when symptoms are mild, is critical for generating reliable data that researchers can use to assess drug efficacy.

Safety, oversight, and ethics in celiac disease trials

Celiac disease clinical trials are overseen by institutional review boards, follow FDA and Good Clinical Practice guidelines, and include ongoing safety monitoring through data safety monitoring boards. The FDA oversees the approval of treatments for celiac disease and sets the regulatory framework that every trial must follow. For a deeper look at the safety record of clinical research, see Are Clinical Trials Safe? What the Data Shows and explore ARI’s participate in a clinical trial page for patient perspectives on the process.

Phase 1 and Phase 2 trials assess short-term side effects and laboratory changes in addition to efficacy. This is especially important for immunotherapies that modulate T-cell responses or target inflammatory pathways, where the balance between dampening disease activity and preserving healthy immune function requires close monitoring. In the KAN-101 Phase 1 trial, for example, common adverse events were mild to moderate and resembled typical gluten exposure symptoms, with no grade 3 or 4 toxicities reported.

Ethical concerns arise when exposing patients with villus atrophy to gluten, which is why gluten challenge protocols are designed with strict dose limits, short durations, and continuous medical oversight. Informed consent documents clearly explain the purpose, procedures, potential risks including symptom flares during gluten challenge, and all alternatives before a participant agrees to take part.

Participants can withdraw from any clinical trial at any time without affecting their regular medical care. ARI maintains dedicated safety reporting procedures and works closely with sponsors, CROs, and physicians to respond promptly to any serious or unexpected events.

Benefits and drawbacks of joining a celiac clinical trial

Potential benefits:

• Access to cutting-edge therapies before they are widely available
• No-cost diagnostics including endoscopy, advanced lab tests, and genetic profiling
• Frequent medical monitoring with specialist oversight
• Opportunity to contribute to celiac disease research that could help future patients
• Financial compensation structured per completed visit

Potential drawbacks:

• Time commitment for multiple visits over weeks to months
• Possible travel to study sites
• Undergoing procedures such as biopsies and endoscopies
• Risk of side effects from investigational medications
• Possibility of receiving placebo in a double blind trial, meaning active drug is not guaranteed

Gluten challenge-based studies may temporarily worsen symptoms such as abdominal pain or diarrhea, and this should be weighed carefully against the potential long-term benefits for the broader celiac community. Many patients who experience symptoms during challenge periods report that they recover within days to weeks of returning to a gluten free diet.

Readers should discuss participation with their gastroenterologist or primary care provider, especially if they have complex medical histories. ARI coordinators can walk patients through what to expect in specific protocols and help them evaluate whether a study is a good fit.

Compensation, costs, and practical considerations

In most regulated clinical trials, all study-related procedures and the investigational drug are provided at no cost to participants. This includes screening labs, endoscopies, imaging, and any required follow-up testing.

Compensation varies by study. The Ritlecitinib trial, for example, offers up to approximately $2,000 in visit-based payments, illustrating how reimbursement is typically structured per completed visit rather than as a lump sum.

Additional practical support often includes:

• Reimbursement for parking, mileage, or public transportation
• Meal vouchers or snacks during long visit days
• Flexible scheduling to accommodate work and family commitments

Regular non-study medical costs, such as primary care visits unrelated to the trial, usually remain the patient’s responsibility and may still be billed to insurance. ARI clearly reviews reimbursement, payment schedules, and any out-of-pocket expectations with participants during the consent process so there are no surprises.

How Advanced Research Institute supports celiac disease research

Advanced Research Institute is a dedicated clinical trial and research site that partners with physicians, sponsors, and CROs to run high-quality, FDA-compliant studies. Learn more about ARI’s approach on the About Our Clinical Trials page.

ARI provides no-cost medical evaluations, diagnostic testing, and close follow-up for eligible celiac patients enrolled in sponsored trials or investigator-initiated protocols. The site has growing experience with immune-mediated and gastrointestinal conditions, positioning it as a resource for early- and late-phase celiac disease clinical trials in Utah, Nevada, and nearby regions.

ARI’s focus on participant safety, strong data quality, and efficient enrollment makes the site an attractive partner for companies developing new celiac therapies. Celiac disease trials aim to develop treatments that are not meant to replace the gluten free diet but to serve as adjuncts that reduce harm from gluten exposure and support mucosal healing.

Referring physicians interested in collaborating on future celiac disease research or referring disease patients with non responsive celiac disease or complex presentations are encouraged to reach out through ARI’s CRO and sponsor partnership page.

Finding and evaluating celiac disease clinical trials near you

Patients and families can find celiac disease clinical trials through several practical channels:

• ClinicalTrials.gov: The most comprehensive public registry of studies, searchable by condition, location, and phase
• National organizations: The Celiac Disease Foundation and Beyond Celiac maintain curated lists of recruiting studies
• Direct contact: Reaching out to local research centers like ARI for information on open and upcoming protocols

When comparing trials, consider these factors:

Factor	Why It Matters
Disease stage targeted	Remission vs. non responsive vs. newly diagnosed
Gluten challenge required	Affects symptom burden during the study
Number of endoscopies	Determines procedural commitment
Visit frequency and duration	Impacts scheduling and travel
Location	Proximity to home or work
Compensation	Varies significantly between studies
Always verify that a trial is registered, IRB-approved, and affiliated with reputable hospitals or research networks. ARI can pre-screen interested celiac patients by phone or online form, review pathology and lab history, and match them with appropriate ongoing or upcoming studies, and its contact information for all locations makes it easy to reach the nearest site.

Keeping personal records organized, including biopsy reports, antibody tests, and dietitian notes, will streamline the eligibility review process and help research coordinators assess your fit quickly.

Future directions in celiac disease therapies and trials

The pipeline of investigational celiac therapies is broader than ever. Ongoing research focuses on adjunct therapies alongside the gluten-free diet for celiac disease, spanning multiple therapeutic categories:

• Barrier and enzyme agents: TAK-062 is an oral enzyme designed to break down gluten in the stomach before it reaches the small intestine. Latiglutenase improves symptoms in seropositive celiac patients through a similar enzymatic approach.
• Immune-modulating antibodies: Amlitelimab and TEV-53408 target specific inflammatory pathways (OX40L and IL-15, respectively) to reduce gluten-driven mucosal injury.
• JAK-pathway inhibitors: Ritlecitinib blocks JAK3/TEC kinase signaling involved in IL-15-mediated immune activation.
• Tolerance-inducing therapies: KAN-101 uses nanoparticles to retrain the immune system to tolerate gluten exposure through liver-targeted delivery of gliadin peptides. VTP-1000 combines gluten peptides with rapamycin in nanoparticles to promote regulatory T cells. Immune tolerance therapies could potentially change the underlying disease response to gluten, moving beyond symptom management toward a fundamental shift in how the immune system reacts.
• Transglutaminase inhibitors: ZED1227 inhibits tissue transglutaminase to prevent gluten-induced intestinal damage by blocking the enzyme that modifies gluten peptides into their most immunogenic forms.

Research is also advancing in digital health tools, AI-assisted endoscopy, and histomolecular profiling that may refine diagnosis and treatment selection for celiac disease patients. The trend toward more standardized trial designs and outcome measures should make it easier to compare results across studies and move candidates into Phase 3 and toward regulatory approval.

As evidence accumulates, future trials may stratify participants by genetic markers, microbiome profiles, or patterns of non responsive disease to personalize therapy. Healthy volunteers may also play a role in early pharmacokinetic and safety studies, though most efficacy trials will continue to require diagnosed celiac patients.

Clinical trials for celiac disease focus on developing non-dietary adjunct therapies, and the pace of innovation suggests that the next several years could bring the first approved pharmacologic treatment for this condition. Researchers at institutions like Columbia University and others are contributing to multicenter efforts, while pharmaceutical companies including Novo Nordisk and Eli Lilly have shown interest in autoimmune and gastrointestinal drug development programs that could eventually intersect with celiac disease research.

How to take the next step with Advanced Research Institute

If you are ready to explore participation in a celiac disease clinical trial, here is how to get started:

1. Call ARI’s dedicated study phone line or complete an online pre-screen form at Participate in a Clinical Trial
2. Ask your physician to send a referral directly to ARI if you prefer coordinated care
3. Book a free consultation to discuss your situation with a research coordinator

After you make contact, ARI’s team will conduct a brief eligibility phone screen, collect your prior biopsy and lab records, and, if appropriate, schedule an in-person or telehealth consultation.

Checklist of information to prepare:

• Date of celiac disease diagnosis
• Biopsy results and pathology reports
• Current medications and supplements
• Length of time on a gluten free diet
• Ongoing symptoms such as abdominal pain, diarrhea, fatigue, or bloating

Reaching out does not obligate you to join a trial. It simply opens a conversation with ARI’s research coordinators and investigators, who can help you understand whether a specific study fits your health situation and goals.

Advanced Research Institute is committed to advancing celiac disease research while prioritizing participant safety, comfort, and respect at every step. Every person who considers a clinical trial, whether they ultimately enroll or not, helps move the field closer to a future where patients with celiac disease have real treatment options beyond diet alone.

We Have a Study on Celiac Disease — See If You Qualify

Interested in Celiac Disease Clinical Trials?

If you’re living with celiac disease and want to learn about treatment options beyond a gluten-free diet, Advanced Research Institute (ARI) may be able to help. ARI connects eligible participants with celiac disease clinical trials in Utah, Nevada, and surrounding areas, including current and upcoming research studies.

Our research team can review your medical history, answer your questions, and help determine whether a clinical trial may be a good fit for you. There is no obligation to participate, and study-related care and procedures are provided at no cost for eligible participants.

Take the next step in celiac disease research. Contact ARI today to learn about clinical trials you may qualify for.