Rectal Tacrolimus in the Treatment of Resistant Ulcerative Proctitis

• Status: Completed
• Trial end date: 2016-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Ulcerative Colitis (UC) is a life-long incurable disease with remissions and exacerbations. Inflammation confined to the rectum occurs in a quarter of patients and can be extremely hard to treat. Many medications have been tried in order to control the inflammation, but they do not always work. One of the newer medications is the immunosuppressing medication, tacrolimus that has been shown to be effective in UC when taken orally. Unfortunately, the oral use of this medication can have numerous serious side effects. In order to overcome these side effects, the use of topical rectal tacrolimus has been examined. Pilot studies in ulcerative proctitis (inflammation confined to the rectum) resistant to conventional therapies have demonstrated a clinical remission in 75% of patients and although the medication was well absorbed through the lining of the bowel, the levels in the blood were very low and no serious side effects were reported. The findings suggest that this preparation is indeed effective for inflammation in the distal bowel and that the method of administration reduces side effects. Further work, however, now needs to be undertaken to validate the original findings.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The University of Western Australia
• Collaborators: Fremantle Hospital and Health Service; Liverpool Hospital, Australia; Royal Adelaide Hospital, Australia; Royal Brisbane and Women's Hospital
• Treatments: Calcineurin Inhibitors; Tacrolimus

Criteria

Inclusion Criteria:

1. Is able to provide informed consent.

2. Is over the age of 18 years

3. Has a diagnosis of ulcerative colitis of over 3 months duration that was confirmed by a specialist gastroenterologist

4. Has inflammation limited to 25cm proximal to the anal verge

5. Has failed to achieve remission with, or be intolerant of, the use of conventional therapy defined as oral and/or rectal 5-Aminosalicylates, and/or oral and rectal steroids

6. Has symptoms of active UC with a Mayo score of between 6 and12

7. Medications:

1. Oral 5-Aminosalicylates: If taking an oral 5-Aminosalicylates the patient has used them continuously for 4 weeks and has been on a stable dose for 2 weeks prior to the screening visit.

2. Oral Corticosteroids: If taking oral corticosteroids the patient has used them continuously for 4 weeks and has been on a stable dose for 2 weeks prior to the screening visit at a dose of ≤30mg.

3. Oral Azathioprine/6MP or Methotrexate: If taking one of these medications the patient has used them for a minimum of 12 weeks and has been on a stable dose for 4 weeks prior to screening.

4. Rectal Preparations; 5-Aminosalicylates and corticosteroids: All rectal preparations have been ceased at least one day prior to Week 0.

8. Has a normal serum potassium levels defined as 3.4-5mmol/L.

9. Has normal renal function defined as a Glomerular Filtration Rate (GFR) >60ml/min.

10. Willing to participate in the study and comply with the proceedings by signing a written informed consent.

11. Free of any clinically significant disease, other than ulcerative colitis, that would interfere with the study's evaluations.

12. Subjects can understand and is able to adhere to the dosing and visit schedules; Agrees to record symptom severity scores, medication times, adverse events and concomitant medications accurately and consistently.

Exclusion Criteria:

1. Has Crohn's disease.

2. Has colitis extending more than 25cm from the anal verge.

3. Has a known hypersensitivity/allergic reaction to tacrolimus.

4. Is pregnant or is breast-feeding.

5. Has unstable, or poorly controlled, hypertension.

6. Has an abnormal serum potassium level defined as outside the range of 3.4-5mmol/L.

7. Has chronic renal failure defined as a Glomerular Filtration Rate <60 ml/min.

8. Is currently using a potassium-sparing diuretic agent.

9. Has received a trial medication within 12 weeks of screening.

10. Has documented HIV infection.

11. Has a known malignancy, a pre-malignant lesion, or any history of malignancy within the past 5 years (excluding squamous and/or basal cell carcinomas).

12. Presence of alcoholism, alcoholic liver disease, or other chronic liver disease.

13. Has known dementia and the inability to understand the trial requirements.