Refractory and/of recurrent ulcerative proctitis
Conditions
Interventions
Product Name: tacrolimus
Pharmaceutical Form: Suppository
INN or Proposed INN: TACROLIMUS
CAS Number: 104987-11-3
Current Sponsor code: none
Other descriptive name: none
Concentration unit: mg milligr
Sponsors
Zon MW
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Endoscopically or histologically proven ulcerative proctitis at least 3 months before randomization. Proctitis is defined as: disease activity to 20 cm beyond the anal verge. Refractory proctitis defined as a failure to at least the use of 5-asa suppositories of a maximum of 1 gram for at least 28 days and recurrent proctitis is defined as relapse within 3 months after stopping of local adequate 5-asa treatment. Endoscopy may have been performed up to 3 weeks before screening, if the endoscopy was well documented and biopsies were taken. Age: 18-70 years and written informed consent. Permitted concomitant therapy: oral aminosalicylates, azathioprine, 6-mercatopurine and methotrexate at stable dose for 12 weeks Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: Use of enemas: 5-asa or beclamethason Infliximab or other anti TNF treatment within 12 weeks prior to randomization Teatment with tacrolimus prior to randomization Treatment with any investigational drug within 12 weeks of randomization Abnormal renal function Pre-existent leucopenia or thrombopenia - Neutrophil count 1,800/mm3 - Platelets 90,000/mm3 Liverfunction tests abnormalities (>2 ULN). Other significant medical illness that might interfere with this study: current malignancy Immunodeficiency syndromes. Any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study such as: - Preexisting psychiatric condition, especially depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt are excluded. Severe depression would include the following: (a) subjects who have been hospitalized for depression, (b) subjects who have received electroconvulsive therapy for depression, or (c) subjects whose depression has resulted in a prolonged absence of work and/or significant disruption of daily functions. Subjects with a history of mild depression may be considered for entry into the protocol provided that a pretreatment assessment of the subject’s mental status supports that the subject is clinically stable and that there is ongoing evaluation of the patient’s mental status during the study - CNS trauma or active seizure disorders requiring medication - Significant cardiovascular dysfunction within the past 6 months (e.g.,angina, congestive heart failure, recent myocardial infarction, severehypertension or significant arrhythmia). - Poorly controlled diabetes mellitus - Significant pulmonary dysfunction/ chronic disease (e.g., chronic obstructive pulmonary disease) - Renal insufficiency (elevated serum creatinin) Pregnancy, Lactation Substance abuse, such as alcohol (80 gm/day), I.V. drugs and inhaled drugs. If the subject has a history of substance abuse, to be considered for inclusion into the protocol, the subject must have abstained from using the abused substance for at least 2 years. Subjects receiving methadone within the past 2 years are also excluded ?Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study. Positive stool culture for enteric pathogens
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary outcome: Number of patients in remission responding to treatment with tacrolimus compared to beclomethason, using the validated Disease Activity Index (D.A.I) and an endoscopic score to compare the disease activity before and after treatment. The primary end point will be the proportion of patients in clinical and endoscopic remission (colitis disease activity index of or =1-point reduction in sigmoidoscopy score from baseline). ;Secondary Objective: Secondary outcomes: Proportion of patients responding (the proportion of patients achieving clinical improvement (defined as a decrease of =3 points from baseline in the total DAI score)); the changes in sigmoidoscopic mucosal appearance (baseline to week 4) Safety and tolerability of tacrolimus and beclomethason. Histopathology from biopsies taken before and after treatment (grading scale (0 _ structural changes only, 1_ chronic inflammation, 2 _ lamina propria neutrophils, 3_ neutrophils in epithelium, 4 _ crypt destruction, 5 _ erosions or ulcers). Quality of life.;Primary end point(s): Number of patients in remission responding to treatment with tacrolimus compared to beclomethason, using the validated Disease Activity Index (D.A.I) and an endoscopic score to compare the disease activity before and after treatment. The primary end point will be the proportion of patients in clinical and endoscopic remission (colitis disease activity index of or =1-point reduction in sigmoidoscopy score from baseline). ;Timepoint(s) of evaluation of this end point: Week 2, 4 and 12: clinical response (DAI) Week 4 endoscopic remission | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: week 2, 4 and 12: safety, clinical response week 4 endoscopic response and histological response week 2,4 and 12:quality of life week 2,4 and 12: safety and tolerability of tacrolimus and beclomethason;Secondary end point(s): Proportion of patients responding (the proportion of patients achieving clinical improvement (defined as a decrease of =3 points from baseline in the total DAI score)); the changes in sigmoidoscopic mucosal appearance (baseline to week 4) Safety and tolerability of tacrolimus and beclomethason. Histopathology from biopsies taken before and after treatment (grading scale (0 _ structural changes only, 1_ chronic inflammation, 2 _ lamina propria neutrophils, 3_ neutrophils in epithelium, 4 _ crypt destruction, 5 _ erosions or ulcers). Quality of life. | — |
Countries
Belgium, Netherlands
Contacts
Public ContactCJ van der Woude
Erasmus MC
Outcome results
None listed