Rectal Tacrolimus in the Treatment of Resistant Ulcerative Proctitis

NCT01418131 | Completed Phase 4 DMC

• 1 other identifier: Tacro001
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Ulcerative Colitis

Keywords

Proctitis; resistant; ulcerative colitis; inflammatory bowel disease

Outcome Measures

Primary Outcomes (1)

• Clinical response

  Clinical response (Mayo Score) of resistant ulcerative proctitis after 8 weeks of rectal tacrolimus therapy

  8 weeks

Secondary Outcomes (6)

• Remission rates

  8 weeks

• Mucosal Healing

  8 weeks

• Changes in the Mayo Score

  8 weeks

• Quality of Life

  8 weeks

• Safety and tolerability

  8 weeks

Study Arms (2)

Rectal tacrolimus

ACTIVE COMPARATOR

Active medications - Rectal tacrolimus made as an ointment at a concentration of 0.5mg/ml 3mls will be applied rectally twice a day

Drug: Rectal tacrolimus

Rectal Placebo

PLACEBO COMPARATOR

Placebo 3ml applied rectally twice a day. Identical to Interventional agent expect for the lack of tacrolimus

Drug: Placebo

Interventions

Rectal tacrolimus DRUG

Rectal tacrolimus made as an ointment at a concentration of 0.5mg/ml with 3 mls will be applied rectally twice a day

Also known as: calcineurin inhibitor

Rectal tacrolimus

Placebo DRUG

Placebo

Also known as: Control Arm

Rectal Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is able to provide informed consent.
• Is over the age of 18 years
• Has a diagnosis of ulcerative colitis of over 3 months duration that was confirmed by a specialist gastroenterologist
• Has inflammation limited to 25cm proximal to the anal verge
• 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
• Has symptoms of active UC with a Mayo score of between 6 and12
• Medications:
• 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.
• 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.
• 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.
• Rectal Preparations; 5-Aminosalicylates and corticosteroids: All rectal preparations have been ceased at least one day prior to Week 0.
• Has a normal serum potassium levels defined as 3.4-5mmol/L.
• Has normal renal function defined as a Glomerular Filtration Rate (GFR) \>60ml/min.
• Willing to participate in the study and comply with the proceedings by signing a written informed consent.
• Free of any clinically significant disease, other than ulcerative colitis, that would interfere with the study's evaluations.

You may not qualify if:

• Has Crohn's disease.
• Has colitis extending more than 25cm from the anal verge.
• Has a known hypersensitivity/allergic reaction to tacrolimus.
• Is pregnant or is breast-feeding.
• Has unstable, or poorly controlled, hypertension.
• Has an abnormal serum potassium level defined as outside the range of 3.4-5mmol/L.
• Has chronic renal failure defined as a Glomerular Filtration Rate \<60 ml/min.
• Is currently using a potassium-sparing diuretic agent.
• Has received a trial medication within 12 weeks of screening.
• Has documented HIV infection.
• 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).
• Presence of alcoholism, alcoholic liver disease, or other chronic liver disease.
• Has known dementia and the inability to understand the trial requirements.

Sponsors & Collaborators

• The University of Western Australia: lead
• Royal Brisbane and Women's Hospital: collaborator
• Royal Adelaide Hospital, Australia: collaborator
• Liverpool Hospital, Australia: collaborator
• Fremantle Hospital and Health Service: collaborator

Study Sites (4)

Liverpool Hospital

Sydney, New South Wales, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

Centre for IBD, Fremantle Hospital

Fremantle, Western Australia, 6160, Australia

Location

Related Publications (5)

• Lawrance IC, Copeland TS. Rectal tacrolimus in the treatment of resistant ulcerative proctitis. Aliment Pharmacol Ther. 2008 Nov 15;28(10):1214-20. doi: 10.1111/j.1365-2036.2008.03841.x. Epub 2008 Aug 30.

  PMID: 18761706 BACKGROUND

• van Dieren JM, van Bodegraven AA, Kuipers EJ, Bakker EN, Poen AC, van Dekken H, Nieuwenhuis EE, van der Woude CJ. Local application of tacrolimus in distal colitis: feasible and safe. Inflamm Bowel Dis. 2009 Feb;15(2):193-8. doi: 10.1002/ibd.20644.

  PMID: 18825773 BACKGROUND

• Hart AL, Plamondon S, Kamm MA. Topical tacrolimus in the treatment of perianal Crohn's disease: exploratory randomized controlled trial. Inflamm Bowel Dis. 2007 Mar;13(3):245-53. doi: 10.1002/ibd.20073.

  PMID: 17206671 BACKGROUND

• Casson DH, Eltumi M, Tomlin S, Walker-Smith JA, Murch SH. Topical tacrolimus may be effective in the treatment of oral and perineal Crohn's disease. Gut. 2000 Sep;47(3):436-40. doi: 10.1136/gut.47.3.436.

  PMID: 10940284 BACKGROUND

• Lawrance IC, Baird A, Lightower D, Radford-Smith G, Andrews JM, Connor S. Efficacy of Rectal Tacrolimus for Induction Therapy in Patients With Resistant Ulcerative Proctitis. Clin Gastroenterol Hepatol. 2017 Aug;15(8):1248-1255. doi: 10.1016/j.cgh.2017.02.027. Epub 2017 Mar 7.

  PMID: 28286194 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative; Proctitis; Inflammatory Bowel Diseases

Interventions

Calcineurin Inhibitors

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Ian C Lawrance, MBBS PhD

  University of Western Australia, Fremantle Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 15, 2011
• First Posted: August 16, 2011
• Study Start: October 1, 2012
• Primary Completion: September 1, 2016
• Study Completion: November 1, 2016
• Last Updated: December 15, 2016

Record last verified: 2016-12

Locations

AU (4)