~63 spots leftby May 2026

Personalized Medication for Severe Ulcerative Colitis

Recruiting in Palo Alto (17 mi)
JB
Overseen byJeffrey Berinstein, MD, MSc
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Berinstein, Jeffrey
Must be taking: Biologics
Must not be taking: CYP3A4 inducers/inhibitors
Disqualifiers: Pregnancy, Toxic megacolon, Severe infection, others
No Placebo Group
Prior Safety Data

Trial Summary

What is the purpose of this trial?

The goal of this trial is to create personalized treatments for each patient admitted to the hospital with acute severe ulcerative colitis (ASUC). The study will test the feasibility and acceptability of these treatment strategies among patients and physicians so that the study team can later do a larger trial to test whether the medication treatment pathways help patients avoid colectomy while ensuring patient's are safe.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients actively receiving strong CYP3A4 inducers or inhibitors, which are certain types of medications, are excluded from the study. It's best to discuss your current medications with the study team to see if any adjustments are needed.

What data supports the effectiveness of the drug for severe ulcerative colitis?

Research shows that intravenous cyclosporine can be effective as a rescue therapy for severe ulcerative colitis, with a short-term success rate of up to 80% in avoiding surgery. However, it is associated with significant toxicity, and there are concerns about early relapse.12345

Is the treatment generally safe for humans?

Cyclosporine, used for severe ulcerative colitis, has shown promise but is associated with significant toxicity and potential for serious infections. Corticosteroids and immunosuppressive agents like cyclosporine have been used extensively, but their benefits must be weighed against possible adverse effects.14678

How is the drug Cyclosporine Injection (IV) unique for treating severe ulcerative colitis?

Cyclosporine Injection (IV) is unique for treating severe ulcerative colitis because it is used as a rescue therapy for patients who do not respond to standard high-dose steroid treatments, showing promising short-term results in avoiding surgery. It is one of the few new therapies that have significantly impacted the management of this condition, despite its potential toxicity.15679

Research Team

JB

Jeffrey Berinstein, MD, MSc

Principal Investigator

University of Michigan

Eligibility Criteria

This trial is for hospitalized patients with acute severe ulcerative colitis, who've had at least one dose of certain biologic treatments. They must be able to take oral meds, follow the study plan including daily symptom tracking, and women must use effective contraception during the study.

Inclusion Criteria

I have been diagnosed with ulcerative colitis confirmed by tests and symptoms.
I am currently in the hospital for ulcerative colitis and will start IV corticosteroids.
Stated willingness to comply with all study procedures and availability for the duration of the study
See 5 more

Exclusion Criteria

I have had or will have a major organ or bone marrow transplant within a year.
I do not have an ongoing infection, including TB.
I am not allergic to methylprednisolone, cyclosporine, tofacitinib, or upadacitinib.
See 25 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive various combinations of Methylprednisolone, Upadacitinib, and Cyclosporine based on their response to initial treatments

Up to 10 days
Daily monitoring during hospital admission

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of clinical response and adverse events

90 days

Extension

Participants may continue to be monitored for long-term outcomes such as colectomy and steroid-free remission

Up to 100 days

Treatment Details

Interventions

  • Cyclosporine Injection (IV) (Immunosuppressant)
  • Cyclosporine Oral Product (Immunosuppressant)
  • Intravenous Methylprednisolone (Corticosteroid)
  • Prednisone Oral Product (Corticosteroid)
  • Upadacitinib Extended Release Oral Tablet (JAK Inhibitor)
Trial OverviewThe trial aims to personalize treatment for ulcerative colitis using Upadacitinib tablets or Cyclosporine orally/injection along with standard steroids. It's testing if these strategies can prevent colectomy (surgical removal of the colon) safely before a larger trial.
Participant Groups
9Treatment groups
Experimental Treatment
Group I: Oral Upadacitinib then Methylprednisolone plus cyclosporine infusionExperimental Treatment3 Interventions
Upadacitinib 30 mg BID for stage 1. If a patient is a non-responder to Upadacitinib 30 mg, then the study team will stop Upadacitinib and initiate Methylprednisolone IV 30mg twice a day plus Cyclosporine (2 milligram/kilogram (mg/kg) per day aiming for levels 200-400 nanograms per milliliter (ng/mL)) for stage 2.
Group II: Oral Upadacitinib then MethylprednisoloneExperimental Treatment3 Interventions
Oral Upadacitinib 30mg BID for stage 1 then for patients that are non-responders, add rescue Methylprednisolone IV 30mg twice a day in addition to continuing Upadacitinib for stage 2.
Group III: Oral UpadacitinibExperimental Treatment1 Intervention
Upadacitinib 30 mg BID
Group IV: Methylprednisolone then UpadacitinibExperimental Treatment2 Interventions
Methylprednisolone IV 30mg twice a day Stage 1 and if determined to be a non-responder to Methylprednisolone, patient will receive rescue Upadacitinib 30mg BID in addition to continuing Methylprednisolone for stage 2
Group V: Methylprednisolone then CyclosporineExperimental Treatment3 Interventions
Methylprednisolone IV 30 mg BID Stage 1 and if determined to be a non-responder to Methylprednisolone, patient will receive rescue Cyclosporine (2milligram/kilogram (mg/kg) per day aiming for levels 200-400 nanograms per milliliter (ng/mL)) in addition to continuing Methylprednisolone for stage 2.
Group VI: Methylprednisolone plus Upadacitinib then increased UpadacitinibExperimental Treatment3 Interventions
Methylprednisolone IV 30mg BID and Oral Upadacitinib 45mg everyday stage 1 and if determined to be a non-responder to Methylprednisolone and 45 mg Oral Upadacitinib, patient will receive rescue Upadacitinib 30mg BID in addition to continuing Methylprednisolone for stage 2.
Group VII: Methylprednisolone plus Upadacitinib then cyclosporineExperimental Treatment3 Interventions
Methylprednisolone IV 30mg BID and Oral Upadacitinib 45mg everyday stage 1 and then Cyclosporine 2 mg/kg per day aiming for levels 200-400ng/mL for stage 2.
Group VIII: Methylprednisolone plus UpadacitinibExperimental Treatment2 Interventions
Methylprednisolone IV 30mg BID plus Upadacitinib 45mg every day.
Group IX: MethylprednisoloneExperimental Treatment2 Interventions
Methylprednisolone Intravenous (IV) 30 milligram (mg) twice a day (BID)

Cyclosporine Injection (IV) is already approved in Canada, Japan for the following indications:

🇨🇦
Approved in Canada as Cyclosporine for:
  • Organ rejection prevention in transplant patients
  • Rheumatoid arthritis
  • Psoriasis
  • Severe ulcerative colitis
🇯🇵
Approved in Japan as Cyclosporine for:
  • Organ rejection prevention in transplant patients
  • Rheumatoid arthritis
  • Psoriasis
  • Severe ulcerative colitis

Find a Clinic Near You

Who Is Running the Clinical Trial?

Berinstein, Jeffrey

Lead Sponsor

Trials
1
Recruited
160+

Findings from Research

In a study of 38 patients with steroid-refractory ulcerative colitis, infliximab was associated with a significantly lower colectomy rate at 3 months (21%) compared to cyclosporine (63%), indicating better short-term efficacy.
At 12 months, infliximab also showed a trend towards lower colectomy rates (37% vs. 68% for cyclosporine), and patients treated with infliximab had shorter hospital stays and lower steroid dependence, suggesting it may be a safer and more effective option.
Infliximab or cyclosporine for acute severe ulcerative colitis: a retrospective analysis.Dean, KE., Hikaka, J., Huakau, JT., et al.[2015]
In a study of nine patients with steroid-refractory ulcerative colitis, oral tacrolimus was effective, with all patients responding within 1-2 weeks and 67% achieving complete remission after 12 weeks.
While oral tacrolimus may serve as a viable alternative to intravenous ciclosporin, careful monitoring for side effects is essential, as two patients experienced severe adverse effects during the treatment.
Effect of oral tacrolimus (FK 506) on steroid-refractory moderate/severe ulcerative colitis.Högenauer, C., Wenzl, HH., Hinterleitner, TA., et al.[2022]
Intravenous cyclosporine showed a high initial response rate of 69% in 16 patients with acute ulcerative colitis who were refractory to steroids, indicating its efficacy as a rescue therapy.
Long-term follow-up revealed that 56% of patients were able to avoid surgery by using a combination of cyclosporine and azathioprine for maintenance, suggesting that this treatment regimen can be effective and relatively safe for managing ulcerative colitis.
Combination immunomodulatory therapy with cyclosporine and azathioprine in corticosteroid-resistant severe ulcerative colitis: the Edinburgh experience of outcome.Campbell, S., Ghosh, S.[2019]

References

Infliximab or cyclosporine for acute severe ulcerative colitis: a retrospective analysis. [2015]
Effect of oral tacrolimus (FK 506) on steroid-refractory moderate/severe ulcerative colitis. [2022]
Efficacy and efficiency of oral microemulsion cyclosporin versus intravenous and soft gelatin capsule cyclosporin in the treatment of severe steroid-refractory ulcerative colitis: an open-label retrospective trial. [2019]
Combination immunomodulatory therapy with cyclosporine and azathioprine in corticosteroid-resistant severe ulcerative colitis: the Edinburgh experience of outcome. [2019]
Intravenous cyclosporin as rescue therapy in severe ulcerative colitis: time for a reappraisal? [2019]
Cyclosporine, tacrolimus, and mycophenolate mofetil in the treatment of inflammatory bowel disease. [2016]
Safety of corticosteroids and immunosuppressive agents in ulcerative colitis. [2019]
Treatment of ulcerative colitis refractory to steroid therapy by oral microemulsion cyclosporine (Neoral). [2018]
[Cyclosporine treatment of patients with active ulcerative colitis refractory to high-dose glucocorticoid]. [2013]