Ulcerative Colitis Clinical Trial
Official title:
A Multi-centre Double Blind Randomised Placebo-controlled Study of the Use of Rectal Tacrolimus in the Treatment of Resistant Ulcerative Proctitis
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.
Status | Completed |
Enrollment | 21 |
Est. completion date | November 2016 |
Est. primary completion date | September 2016 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
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. |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Australia | Royal Adelaide Hospital | Adelaide | South Australia |
Australia | Royal Brisbane and Women's Hospital | Brisbane | Queensland |
Australia | Centre for IBD, Fremantle Hospital | Fremantle | Western Australia |
Australia | Liverpool Hospital | Sydney | New South Wales |
Lead Sponsor | Collaborator |
---|---|
The University of Western Australia | Fremantle Hospital and Health Service, Liverpool Hospital, Australia, Royal Adelaide Hospital, Australia, Royal Brisbane and Women's Hospital |
Australia,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Clinical response | Clinical response (Mayo Score) of resistant ulcerative proctitis after 8 weeks of rectal tacrolimus therapy | 8 weeks | No |
Secondary | Remission rates | Remission rates (Mayo Score) of resistant ulcerative proctitis after 8 weeks of rectal tacrolimus | 8 weeks | No |
Secondary | Mucosal Healing | Effect of rectal tacrolimus on mucosal healing after 8 weeks of therapy | 8 weeks | No |
Secondary | Changes in the Mayo Score | Changes in the modified Mayo Score between tacrolimus and control groups over 8 weeks of therapy | 8 weeks | No |
Secondary | Quality of Life | Changes in quality of life by the Inflammatory Bowel Disease Questionnaire (IBDQ) between tacrolimus and control groups over 8 weeks of therapy | 8 weeks | No |
Secondary | Safety and tolerability | Safety and tolerability of rectal tacrolimus over 8 weeks of therapy | 8 weeks | Yes |
Secondary | Cytokine Expression | Changes in cytokine expression in mucosal biopsies following rectal tacrolimus therapy | 8 weeks | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05702879 -
Combined Microbiota and Metabolic Signature in Ulcerative Colitis Predicts Anti-Inflammatory Therapy Success
|
||
Not yet recruiting |
NCT05953402 -
A Study of Ozanimod in Pregnant Women With Ulcerative Colitis and Their Offspring
|
||
Recruiting |
NCT05316584 -
A Novel Remote Patient and Medication Monitoring Solution to Improve Adherence and PerSiStence With IBD Therapy
|
N/A | |
Recruiting |
NCT03950232 -
An Extension Study for Treatment of Moderately to Severely Active Ulcerative Colitis
|
Phase 3 | |
Completed |
NCT03124121 -
Study of the Golimumab Exposure-Response Relationship Using Serum Trough Levels
|
Phase 4 | |
Not yet recruiting |
NCT06100289 -
A Study of Vedolizumab in Children and Teenagers With Ulcerative Colitis or Crohn's Disease
|
Phase 3 | |
Withdrawn |
NCT04209556 -
A Study To Evaluate The Safety And Efficacy Of PF-06826647 In Participants With Moderate To Severe Ulcerative Colitis
|
Phase 2 | |
Terminated |
NCT00061282 -
Clotrimazole Enemas for Pouchitis in Children and Adults
|
Phase 1/Phase 2 | |
Recruiting |
NCT04398550 -
SCD vs. Mediterranean Diet Therapy in Ulcerative Colitis
|
N/A | |
Recruiting |
NCT04314375 -
Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Budesonide Extended-release Tablets in Pediatric Subjects Aged 5 to 17 Years With Active, Mild to Moderate Ulcerative Colitis
|
Phase 4 | |
Active, not recruiting |
NCT04857112 -
Study Evaluating Efficacy and Safety of Amiselimod (MT-1303) in Mild to Moderate Ulcerative Colitis
|
Phase 2 | |
Completed |
NCT05051943 -
A Study of the Real-world Use of an Adalimumab Biosimilar and Evaluation of Nutritional Status on the Therapeutic Response
|
||
Active, not recruiting |
NCT04033445 -
A Study of Guselkumab in Participants With Moderately to Severely Active Ulcerative Colitis
|
Phase 2/Phase 3 | |
Recruiting |
NCT05428345 -
A Study of Vedolizumab SC Given to Adults With Moderate to Severe Ulcerative Colitis or Crohn's Disease in South Korea
|
||
Active, not recruiting |
NCT06221995 -
Energy Expenditure in Patients With Ulcerative Colitis Undergoing Surgery
|
||
Recruiting |
NCT04767984 -
Testing Atorvastatin to Lower Colon Cancer Risk in Longstanding Ulcerative Colitis
|
Phase 2 | |
Completed |
NCT02508012 -
Medico-economic Evaluation of the Therapeutic Drug Monitoring of Anti-TNF-α Agents in Inflammatory Bowel Diseases
|
N/A | |
Recruiting |
NCT06071312 -
FMT in Patients With Recurrent CDI and Ulcerative Colitis: Single Infusion Versus Sequential Approach
|
Phase 1/Phase 2 | |
Completed |
NCT03760003 -
Dose-Ranging Phase 2b Study of ABX464 in Moderate to Severe Ulcerative Colitis
|
Phase 2 | |
Not yet recruiting |
NCT05539625 -
Mini-MARVEL - Mitochondrial Antioxidant Therapy in Ulcerative Colitis
|
Phase 2 |