The purpose of this research study is to evaluate what type of treatment will be beneficial for people with Crohn's disease and difficult to treat inflammation in the small bowel. Current therapies are used to control the inflammation due to Crohn's disease in your digestive tract. In some patients, those therapies are not sufficient to fully treat the disease. This objective of this study is to evaluate the efficacy of a different type of therapy, tirzepatide, that may promote healing of the affected intestinal segment. To evaluate the efficacy of this medication, a member of the research team will ask patients questions about how they feel and observe whether this medication heals the their bowel at colonoscopy. A member of the research team will also use blood samples, stool samples and samples of the small intestine taken during a colonoscopy to understand how tirzepatide helps heal the intestine.

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