A Study to Evaluate Intra-arterial Delivery of Mesenchymal Stem Cells for Luminal Ulcerative Colitis

Overview

About this study

Ulcerative Colitis (UC) is a chronic inflammatory disease affecting the mucosal lining of the colon and rectum and the incidence is increasing, but the etiology remains unknown. Patients may require a proctocolectomy due to refractory disease. Prior to an operation, UC is treated with antibiotic therapy, immunomodulatory therapy and immunosuppressive agents. While there is an increasing number of approved biologics for the treatment of UC, there are many patients that still suffer from refractory disease. Thus, alternative mechanisms of therapy are desperately needed.

Treatments that have the potential to reduce mucosal inflammation could alleviate the pathology of luminal UC. This trial will use arterially delivered mesenchymal stem cells (MSCs) to produce these regenerative signals allowing for mucosal healing. This study will enroll patients with medically refractory moderate to severe inflammatory UC who are or plan to be scheduled for a colectomy. Patients enrolled will be those who failed all attempts at standard treatment including antibiotics, corticosteroids, immunomodulator, and/or biologic therapy.

Participants will undergo screening for study, if eligible, participants will be dosed with 15 million or 30 million cells will be administered via IA delivery with interventional radiology. Participant study visits after study intervention includes visits on: Day 1, Week 1, Week 2, Week 8, Week 24, Week 52, and Week 104.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Males and females, 18-65 years of age.
  • Moderate to Severe medically refractory inflammatory ulcerative colitis:
    • as defined by a an Adapted Mayo Score of 5 to 9 points;
    • including an endoscopic sub-score of 2 or 3.
  • Concurrent therapies with corticosteroids, 5-ASA drugs, thiopurines, MTX, antibiotics, anti-TNF, and anti-integrin therapy are permitted.
  • To meet the definition of refractory UC, all patients must have failed at least 2 standard FDA approved medications for the treatment of UC:
    • Current standard therapy includes 5-ASA products, thiopurines, anti-TNF therapy, ustekinumab, vedolizumab, and tofacitinib (i.e., all FDA approved therapies for UC);
    • Refractory and failure to response is defined as continued symptoms despite 12 weeks of therapy at FDA approved doses by product necessitating change in medical strategy or referral for colectomy.
  • All patients should have undergone a colonoscopy in last 12 months to rule out malignant or premalignant condition.
  • Female subjects that are of child bearing potential must to agree to use effective contraception method(s) for the duration of the study.
  • Hemoglobin must be greater than 8.
  • INR must be less than 1.5.
  • Ability to comply with protocol.
  • Competent and able to provide written informed consent..

Exclusion Criteria:

  • Inability to give informed consent.
  • Clinically significant medical conditions within the six months before administration of MSC; e.g., myocardial infarction, active angina, congestive heart failure or other conditions that would, in the opinion of the investigators, compromise the safety of the patient.
  • Specific exclusions: Known history of hepatitis B, C, or HIV.
  • Patients that have had a partial colectomy.
  • Patients that have underlying vasculitis or have been diagnosed with an underlying condition that predisposes to developing blood clots.
  • History of cancer including melanoma (with the exception of localized skin cancers).
  • Investigational drug within thirty (30) days of baseline.
  • History of clinically significant auto-immunity (other than UC) or any previous example of fat-directed autoimmunity:
    • Please note that auto-immunity is defined as a systemic immune mediated disease for which the antigen is known or unknown. Autoimmune diseases other than UC are excluded. Extraintestinal manifestations of UC (specifically joint inflammation, eye inflammation, PSC, skin manifestations; i.e., pyoderma gangrenosum, erythema nodosum) will be allowable.
  • Allergic to local anesthetics.
  • Pregnant patients or trying to become pregnant or breast feeding.
  • Neoplasia of the colon and preoperative biopsy.
  • C. Difficile infection within 30 days of study injection.
  • Diagnosis of indeterminate colitis or suspicion of CD.
  • Subjects with fulminant colitis, toxic megacolon, with ostomy, or ileoanal pouch.
  • History or demonstration of pathology related to adipose tissue
  • Any other indication determined by the PI to be counter indicated for participation on this trial.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

William Faubion, M.D.

Open for enrollment

Contact information:

Jessica Friton

(507) 284-0495

Friton.Jessica@mayo.edu

More information

Publications

Publications are currently not available