Tirzepatide to heal small-bowel Crohn's disease after failure of advanced therapies

Moving Beyond Inflammation as a Therapeutic Target for Crohn's Disease

This trial will test whether tirzepatide can help heal ileal or ileocolonic Crohn's disease in adults whose inflammation has not responded to at least two advanced treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Washington University School of Medicine (Academic / other)
• Drugs / interventions: Infliximab, Adalimumab, Certolizumab, Golimumab, vedolizumab, Ustekinumab, Risankizumab, Guselkumab, Mirikizumab, Upadacitinib, radiation
• Locations: 3 sites (Beverly Hills, California and 2 other locations)
• Trial ID: NCT06976853 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial enrolls adults with confirmed Crohn's disease and active ileal or ileocolonic inflammation despite prior treatment with at least two advanced-class drugs. Eligible participants receive tirzepatide alongside standard-of-care monitoring and undergo symptom questionnaires, colonoscopic assessment of the ileum, and collection of blood, stool, and intestinal biopsy samples. Endoscopic healing (using SES-CD scoring) and biological markers from tissue, blood, and stool will be used to measure treatment effect and explore mechanisms. The study is conducted at three U.S. academic centers with periodic clinical visits and at least one colonoscopy to document intestinal healing.

Who should consider this trial

Good fit: Adults 18–80 with confirmed Crohn's disease involving the ileum or ileocolon, active endoscopic inflammation (Ileal SES-CD >4 and ulcer subscore >1), and documented failure of at least two advanced-class drugs are the intended participants.

Not a fit: Patients whose disease is well controlled on current therapy, whose inflammation is limited to the colon rather than the small bowel, pregnant women, or those with contraindications to tirzepatide are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, tirzepatide could promote healing of affected small-bowel segments and offer a new option for patients who have not responded to multiple advanced therapies.

How similar studies have performed: This approach is relatively novel for Crohn's disease: tirzepatide has demonstrated metabolic and weight-loss benefits in diabetes and obesity studies but has not been widely tested for healing small-bowel Crohn's inflammation.

Eligibility criteria

Inclusion Criteria:

1. Subjects 18 to 80 years of age, inclusive, at the time of consent
2. Confirmed diagnosis of Crohn's disease based on documented findings on endoscopy and histopathology
3. Active ileal or ileocolonic inflammation on colonoscopy defined as

   1\. Ileal SES-CD \> 4 with ulcer subscore \> 1 (ulcers \> 5mm)
4. Failure to respond to (primary or secondary non-response) at least 2 advanced class drugs, without evidence of immunogenicity (anti-TNFa only). Must have been at least 6 months optimized on most recent therapy without corticosteroids.

   1. Anti-TNF: Infliximab, Adalimumab, Certolizumab, Golimumab
   2. Anti-integrin agent: vedolizumab
   3. Anti-IL12/23 agent: Ustekinumab
   4. Anti-IL23: Risankizumab, Guselkumab, Mirikizumab
   5. JAK inhibitor: Upadacitinib
5. In post surgical patients, must be at least 6 months post-op with endoscopic evidence of ileal disease
6. In females: compliance to recommended birth control requirements

Exclusion Criteria:

1. Age \< 18 or \> 80 years
2. Pregnant or Breastfeeding female
3. Diagnosis of ulcerative colitis, indeterminate colitis, microscopic colitis, ischemic colitis, radiation colitis, diverticular disease-associated colitis, toxic megacolon, active infectious colitis or positive test for Clostridioides Difficile toxin at screening
4. BMI \< 25
5. Current or previous diagnosis of anorexia nervosa
6. Type 1 or Type 2 diabetes
7. Use of concomitant hypoglycemic agents
8. Personal or family history of medullary thyroid carcinoma
9. History of multiple endocrine neoplasia
10. Known serious hypersensitivity to tirzepatide or any of its excipients
11. Have functional or post-operative short-bowel syndrome
12. Had intestinal resection ≤ 24 weeks prior to inclusion or other intra-abdominal surgeries ≤ 12 weeks prior to study inclusion
13. Active treatment with steroids\*
14. Positive stool test for parasites, C. Diff or stool culture for pathologic bacteria within 30 days prior to enrollment
15. Current stricture not passable with an endoscope
16. Impending need for surgery per investigator
17. Have an ileostomy or a colostomy
18. In females: refusal to comply to recommended birth control requirements \*Corticosteroids have metabolic and hormonal effects which we are concerned may interfere with study outcomes and metabolic changes in the population. This exclusion criteria will allow the study population to be standardized across all patients

Where this trial is running

Beverly Hills, California and 2 other locations

• Cedars-Sinai Medical Center — Beverly Hills, California, United States (Not_yet_recruiting)
• Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)
• Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Parakkal Deepak, MBBS, MS — Washington University School of Medicine GI Division
• Study coordinator: Monique Lavalas Bright

Conditions Crohn Disease