Rectal Tacrolimus in the Treatment of Resistant Ulcerative Proctitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by The University of Western Australia
Sponsor:
Collaborators:
Mater Health Services' Adult Hospital, Brisbane
Concord Hospital
The Canberra Hospital
Royal Prince Alfred Hospital, Sydney, Australia
Information provided by (Responsible Party):
Ian Lawrance, The University of Western Australia
ClinicalTrials.gov Identifier:
NCT01418131
First received: August 15, 2011
Last updated: November 8, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Ulcerative Colitis
Drug: Rectal tacrolimus
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-centre Double Blind Randomised Placebo-controlled Study of the Use of Rectal Tacrolimus in the Treatment of Resistant Ulcerative Proctitis

Resource links provided by NLM:


Further study details as provided by The University of Western Australia:

Primary Outcome Measures:
  • Clinical response [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Clinical response (Mayo Score) of resistant ulcerative proctitis after 8 weeks of rectal tacrolimus therapy


Secondary Outcome Measures:
  • Remission rates [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Remission rates (Mayo Score) of resistant ulcerative proctitis after 8 weeks of rectal tacrolimus

  • Mucosal Healing [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Effect of rectal tacrolimus on mucosal healing after 8 weeks of therapy

  • Changes in the Mayo Score [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Changes in the modified Mayo Score between tacrolimus and control groups over 8 weeks of therapy

  • Quality of Life [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Changes in quality of life by the Inflammatory Bowel Disease Questionnaire (IBDQ) between tacrolimus and control groups over 8 weeks of therapy

  • Safety and tolerability [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Safety and tolerability of rectal tacrolimus over 8 weeks of therapy

  • Cytokine Expression [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Changes in cytokine expression in mucosal biopsies following rectal tacrolimus therapy


Estimated Enrollment: 50
Study Start Date: October 2012
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rectal tacrolimus
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 tacrolimus made as an ointment at a concentration of 0.5mg/ml with 3 mls will be applied rectally twice a day
Other Name: calcineurin inhibitor
Placebo Comparator: Rectal Placebo
Placebo 3ml applied rectally twice a day. Identical to Interventional agent expect for the lack of tacrolimus
Drug: Placebo
Placebo
Other Name: Control Arm

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 week 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01418131

Locations
Australia, Australian Capital Territory
Canberra Hospital Recruiting
Canberra, Australian Capital Territory, Australia
Contact: Paul Pavli, MBBS PhD       Paul.Pavli@act.gov.au   
Principal Investigator: Paul Pavli, MBBS PhD         
Australia, New South Wales
Concord Repatriation General Hospital Not yet recruiting
Sydney, New South Wales, Australia
Contact: Rupert Leong, MBBS MD    +61 (02) 9767 5000    Rupert.Leong@swsahs.nsw.gov.au   
Principal Investigator: Rupert Leong, MBBS MD         
Royal Prince Alfred Hospital Not yet recruiting
Sydney, New South Wales, Australia
Contact: Wawick Selby, MBBS    0295156111    warwicks@sydney.edu.au   
Principal Investigator: Wawick Selby, MBBS         
Australia, Queensland
Royal Brisbane and Women's Hospital Not yet recruiting
Brisbane, Queensland, Australia
Contact: Graham Radford-Smith    07 3362 0171    Graham.Radford-Smith@qimr.edu.au   
Principal Investigator: Graham Radford-Smith, MB ChB DPhil         
The Mater Hospital Not yet recruiting
Brisbane, Queensland, Australia
Contact: Timothy Florin, MBBS PhD    07 3163 1111    t.florin@uq.edu.au   
Principal Investigator: Timothy Florin, MBBS PhD         
Australia, South Australia
Royal Adelaide Hospital Not yet recruiting
Adelaide, South Australia, Australia
Contact: Jane Andrews, MBBS PhD    +61 8 8222 5207    jane.andrews@health.sa.gov.au   
Principal Investigator: Jane Andrews, MBBS PhD         
Flinders Medical Centre Recruiting
Adelaide, South Australia, Australia
Contact: Peter Bampton, MBBS PhD       Petpeter.bampton@flinders.edu.au   
Principal Investigator: Peter Bampton, MBBS PhD         
Australia, Victoria
St Vincent's Hospital Recruiting
Fitzroy, Victoria, Australia, 3060
Contact: Michael Kamm, MBBS PhD       Micmkamm@unimelb.edu.au   
Principal Investigator: Michael Kamm, MBBS PhD         
Australia, Western Australia
Centre for IBD, Fremantle Hospital Recruiting
Fremantle, Western Australia, Australia, 6160
Contact: Ian Lawrance, MBBS PHD    61894313333    ian.lawrance@uwa.edu.au   
Principal Investigator: Ian C Lawrance, MBBS PhD         
Sponsors and Collaborators
The University of Western Australia
Mater Health Services' Adult Hospital, Brisbane
Concord Hospital
The Canberra Hospital
Royal Prince Alfred Hospital, Sydney, Australia
Investigators
Principal Investigator: Ian C Lawrance, MBBS PhD University of Western Australia, Fremantle Hospital
  More Information

Publications:
Responsible Party: Ian Lawrance, professor, The University of Western Australia
ClinicalTrials.gov Identifier: NCT01418131     History of Changes
Other Study ID Numbers: Tacro001
Study First Received: August 15, 2011
Last Updated: November 8, 2012
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by The University of Western Australia:
Proctitis
resistant
ulcerative colitis
inflammatory bowel disease

Additional relevant MeSH terms:
Colitis
Ulcer
Colitis, Ulcerative
Proctitis
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Rectal Diseases
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014