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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01418131




Registration number
NCT01418131
Ethics application status
Date submitted
15/08/2011
Date registered
16/08/2011
Date last updated
15/12/2016

Titles & IDs
Public title
Rectal Tacrolimus in the Treatment of Resistant Ulcerative Proctitis
Scientific title
A Multi-centre Double Blind Randomised Placebo-controlled Study of the Use of Rectal Tacrolimus in the Treatment of Resistant Ulcerative Proctitis
Secondary ID [1] 0 0
Tacro001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rectal tacrolimus
Treatment: Drugs - Placebo

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

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


Treatment: Drugs: 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

Treatment: Drugs: Placebo
Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Clinical response
Timepoint [1] 0 0
8 weeks
Secondary outcome [1] 0 0
Remission rates
Timepoint [1] 0 0
8 weeks
Secondary outcome [2] 0 0
Mucosal Healing
Timepoint [2] 0 0
8 weeks
Secondary outcome [3] 0 0
Changes in the Mayo Score
Timepoint [3] 0 0
8 weeks
Secondary outcome [4] 0 0
Quality of Life
Timepoint [4] 0 0
8 weeks
Secondary outcome [5] 0 0
Safety and tolerability
Timepoint [5] 0 0
8 weeks
Secondary outcome [6] 0 0
Cytokine Expression
Timepoint [6] 0 0
8 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2016
Sample size
Target
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Sydney
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Centre for IBD, Fremantle Hospital - Fremantle
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
6160 - Fremantle

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Western Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal Brisbane and Women's Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Royal Adelaide Hospital, Australia
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Liverpool Hospital, Australia
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Fremantle Hospital and Health Service
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01418131
Trial related presentations / publications
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Ian C Lawrance, MBBS PhD
Address 0 0
University of Western Australia, Fremantle Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01418131