Personalized Medication for Severe Ulcerative Colitis
Recruiting in Palo Alto (17 mi)
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?
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
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
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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.
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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 United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Cyclosporine for:
- Organ rejection prevention in transplant patients
- Rheumatoid arthritis
- Psoriasis
- Severe ulcerative colitis
🇪🇺 Approved in European Union as Cyclosporin for:
- Organ rejection prevention in transplant patients
- Rheumatoid arthritis
- Psoriasis
- Severe ulcerative colitis
- Atopic dermatitis
🇨🇦 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
Research Locations NearbySelect from list below to view details:
University of MichiganAnn Arbor, MI
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Who Is Running the Clinical Trial?
Berinstein, JeffreyLead Sponsor
References
Infliximab or cyclosporine for acute severe ulcerative colitis: a retrospective analysis. [2015]Medical treatment of steroid-refractory ulcerative colitis (UC) is limited to either cyclosporine or infliximab. Studies comparing cyclosporine with either placebo or intravenous methylprednisone showed promise for cyclosporine, but associated it with significant toxicity. There is conflicting, but increasingly positive evidence for using infliximab. There are no studies directly comparing these two treatments. Our aim was to compare the outcomes of patients with steroid-refractory UC treated with either intravenous cyclosporine or infliximab.
Effect of oral tacrolimus (FK 506) on steroid-refractory moderate/severe ulcerative colitis. [2022]Steroid refractory ulcerative colitis is most commonly treated with intravenous ciclosporin to avoid colectomy. In search for an alternative drug that can be administered orally we investigated oral tacrolimus (FK 506) for this indication.
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]We have used cyclosporin to treat patients with acute steroid-resistant ulcerative colitis since the beginning of 1991. Of the 55 patients so far elected for treatment, 40 received the drug intravenously at 2 mg/kg/day for 14 days, with the responders being maintained on traditional soft-gelatin-capsule cyclosporin at a dose of 6-8 mg/kg/day for 6 months; the remaining 15 received oral microemulsion cyclosporin, 5 mg/kg/day, for 3 months. The doses were titrated to ensure whole-blood drug concentrations of 60-240 ng/ml, with levels of approximately 200 ng/ml being attained by both regimens. One-hundred percent of the patients receiving oral microemulsion cyclosporin and 65% of those receiving the intravenous regimen achieved a short-term response (p = 0.011). Both the responder subsets received additional azathioprine and relapsed on treatment with the same frequency of 40%. However, 17% of the patients who received intravenous cyclosporin developed major toxicity (including one fatality), whereas no major toxicity was observed in the oral microemulsion cyclosporin group. The microemulsion formulation was therefore more effective than intravenous cyclosporin in achieving the short-term remission of steroid-unresponsive ulcerative colitis. As the maintenance drug, it led to the same frequency of disease relapse as traditional oral cyclosporin. However, because it did not involve invasive in-hospital procedures or cause major toxicity, it was more efficient than the combination of the intravenous and traditional oral drug.
Combination immunomodulatory therapy with cyclosporine and azathioprine in corticosteroid-resistant severe ulcerative colitis: the Edinburgh experience of outcome. [2019]Cyclosporine is a fungal metabolite and a powerful immunosuppressant. While response to intravenous steroids in severe ulcerative colitis is in excess of 60%, the remainder of patients are left with the options of curative panproctocolectomy or administration of intravenous rescue therapy with cyclosporine. There have been conflicting reports on the efficacy of intravenous cyclosporine in acute ulcerative colitis, and there are serious concerns about potential toxicity and opportunistic infections such as Pneumocystis carnii pneumonia. There are also concerns about early relapse and colectomy following cyclosporine rescue. To date there has been a paucity of data available to help guide the gastroenterologist in the use of cyclosporine and the maintenance of remission once achieved.
Intravenous cyclosporin as rescue therapy in severe ulcerative colitis: time for a reappraisal? [2019]Intravenous cyclosporin is the only new therapy in recent years to have made a significant impact on the management of acute severe ulcerative colitis (UC). It is increasingly recommended for use in patients who prove refractory to the standard regimen of intravenous (i.v.) and rectal hydrocortisone but do not warrant immediate surgery. This practice is based on uncontrolled and controlled studies which suggest a short-term efficacy of 80% and long-term efficacy of 60% in avoiding colectomy.
Cyclosporine, tacrolimus, and mycophenolate mofetil in the treatment of inflammatory bowel disease. [2016]In the past decade, immunosuppressive drugs have come to play an integral role in the treatment of patients with inflammatory bowel disease. Cyclosporine, microemulsion cyclosporine, tacrolimus, and mycophenolate mofetil can be considered for the treatment of patients with refractory inflammatory Crohn's disease, fistulizing Crohn's disease, and severe ulcerative colitis. This article reviews the use of cyclosporine, tacrolimus, and mycophenolate mofetil in patients with inflammatory bowel disease, with emphasis on pharmacology, results in controlled clinical trials, and safety, and issues related to dosing and toxicity monitoring.
Safety of corticosteroids and immunosuppressive agents in ulcerative colitis. [2019]For many years, corticosteroids have been the mainstay for treating acute ulcerative colitis. In patients with refractory disease, immunosuppressive therapy may be indicated, including azathioprine or its metabolite 6-mercaptopurine, cyclosporin and possibly methotrexate. Their benefits in ulcerative colitis must be weighed up against their possible adverse effects, the availability of surgical cure for this condition, and the long-term risk of carcinoma complicating colitis that applies in patients with chronic extensive disease. Information about the safety of corticosteroids and immunosuppressive agents has accumulated as a result of their extensive use in inflammatory bowel disease, organ transplantation and various other disorders.
Treatment of ulcerative colitis refractory to steroid therapy by oral microemulsion cyclosporine (Neoral). [2018]Intravenous cyclosporine is active in 60% to 80% of patients with ulcerative colitis (UC) who failed to respond to intravenous corticosteroids. Several studies have suggested that cyclosporine in microemulsion form (Neoral) has some efficacy in this setting, but the optimal dose, blood level, time to response, and remission need to be better defined. The aim of this study was to evaluate the response to Neoral and its toxicity in active corticosteroid-refractory UC.
[Cyclosporine treatment of patients with active ulcerative colitis refractory to high-dose glucocorticoid]. [2013]In around 30-40% of patients with acute severe ulcerative colitis the disease is refractory to treatment with high-dose glucocorticoids. Adding intravenous cyclosporine to the therapy in these patients has shown encouraging short-term results. Case notes of twenty-three acutely ill patients, who received intravenous cyclosporine during the period 1992 to 1998 due to failure of high-dose glucocorticoid (n = 20) or due to medical complications (n = 3) which made surgery difficult, were reviewed. Eight patients had their first episode of ulcerative colitis whereas 15 had relapse or chronic active disease. Cyclosporine (4 mg/kg/dag) was added to glucocorticoid treatment after a median of 11 days. Clinical remission was achieved in 13 patients (57%) after a median of nine days, of these five subsequently underwent surgery. Ten did not obtain remission and went to surgery. Approximately a third of acutely ill ulcerative colitis patients refractory to standard treatment with high-dose glucocorticoids will benefit from intravenous cyclosporine in the longer term.