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Trial registered on ANZCTR


Registration number
ACTRN12612001067864
Ethics application status
Approved
Date submitted
4/10/2012
Date registered
5/10/2012
Date last updated
12/05/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Antidepressants to maintain remission and improve quality of life and mental health in Crohn’s disease (CD) patients: A pilot randomised controlled trial
Scientific title
A randomised controlled pilot trial to evaluate the efficacy of fluoxetine in maintaining remission in Crohn's disease
Secondary ID [1] 281330 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
inflammatory bowel disease 287548 0
Condition category
Condition code
Oral and Gastrointestinal 287873 287873 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Fluoxetine was selected based on previous research showing its anti-inflammatory properties in humans, and in relation to IBD based on findings of studies examining animal models of colitis. Previous human studies have recommended a dose of 20mg daily (which is considered a low therapeutic dose when used in the treatment of depression) and the length of study to be at least 3 to 8 weeks in order to show fluoxetine’s efficacy. However, the present study was concerned with the longitudinal efficacy of fluoxetine as an agent modifying the course of IBD and psychological parameters, and thus treatment was provided for 12 months with the dose of 20mg daily administered orally. A Generic Health brand of fluoxetine was purchased from the RAH pharmacy and the placebo was an inactive tablet produced by Pharmaceutical Packaging Professionals as recommended by the same pharmacy. Treatment with fluoxetine is currently not part of standard practice in gastroenterology, however, in our case-note audit we demonstrated that a life-time use of antidepressants in our IBD patients is approx. 30% and thus many patients would have been exposed to antidepressants, including fluoxetine. In the audit, we did not identify any major adverse-events related to the use of antidepressants in IBD and the interview we conducted with IBD patients currently taking antidepressants demonstrated their acceptance by this population.
Intervention code [1] 285792 0
Treatment: Drugs
Comparator / control treatment
Placebo (dummy tablet)
Control group
Placebo

Outcomes
Primary outcome [1] 288093 0
The primary outcome measure was a significant difference in means and proportions of participants in remission on the Crohn's Disease Activity Index (CDAI).
Timepoint [1] 288093 0
3, 6 and 12 months.
Primary outcome [2] 288094 0
The primary outcome measure was a significant difference in means on the World Health Organisation Quality of Life measure (WHOQoL).
Timepoint [2] 288094 0
3, 6 and 12 months.
Secondary outcome [1] 299420 0
The secondary outcome measures was a difference in means on the fecal calprotectin test.
Timepoint [1] 299420 0
3, 6 and 12 months.
Secondary outcome [2] 299422 0
The secondary outcome measures was a difference in means on the Hospital Anxiety and Depression Scale (HADS).
Timepoint [2] 299422 0
3, 6 and 12 months.
Secondary outcome [3] 299437 0
The secondary outcome measures were differences in means of cytokine/chemokines (changes towards more anti-inflammatory balance) assessed on the serum assays.
Timepoint [3] 299437 0
3, 6 and 12 months.

Eligibility
Key inclusion criteria
Inclusion criteria
Patients had to meet ALL of the following criteria:
1). Established diagnosis of CD;
2). Remission or only mild symptoms of CD (CDAI <150);
3). Have flared CD in the last 12 months (as documented by their treating doctor and demonstrated by either raised inflammatory markers, augmented therapy, high CDAI or calprotectin);
4). Be on stable dose of all their current CD therapies for 12 weeks;
5). Be 18 years old or older;
6). Have a sufficient knowledge of English to understand and answer questionnaires.
7). Have the ability to consent to the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria
Patients were excluded if they met ANY of the following:
1). Have serious uncontrolled mental illness (e.g. schizophrenia) or are alcohol/substance dependant;
2). Currently taking antidepressants;
3). Currently receiving psychotherapy;
4). Currently taking steroids >15mg or equivalent;
5). Are allergic to fluoxetine or any component of placebo;
6). Are pregnant or breastfeeding;
7). Have cognitive impairment.

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)
Patients meeting the inclusion criteria and providing consent to participate in the trial were randomly assigned to receive either fluoxetine 20mg daily or placebo. Patients in both treatment arms remained on their current IBD treatment. We used stratified randomisation where the strata were sex (male / female) and the Hospital Anxiety and Depression (HADS) score (>7 or <7 on either of the subscales). After initial screening, participants were assigned to one of 4 categories and within each, 13 participants were assigned to controls and 14 to the experimental group. Sealed envelopes with these allocations were prepared by the study’s statistician (AE) who had no patient contact. The randomisation scheme was generated by a computer program designed for this purpose.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple computer-generated sequence involving a matrix of random numbers. Separate randomisation tables will be used for each hospital. Proportion 1:1.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 5792 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 5793 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 5813 0
5001
Recruitment postcode(s) [2] 5814 0
5042

Funding & Sponsors
Funding source category [1] 286094 0
Charities/Societies/Foundations
Name [1] 286094 0
Broad Foundation
Address [1] 286094 0
10900 Wilshire Boulevard Twelfth Floor
Los Angeles, California 90024
Country [1] 286094 0
United States of America
Primary sponsor type
University
Name
University of South Australia
Address
School of Nursing and Midwifery
GPO Box 2471, Adelaide 5001, SA
Country
Australia
Secondary sponsor category [1] 284906 0
Hospital
Name [1] 284906 0
Royal Adelaide Hospital
Address [1] 284906 0
North Tce, Adelaide 5000, SA
Country [1] 284906 0
Australia
Other collaborator category [1] 277104 0
Hospital
Name [1] 277104 0
Flinders Medical Centre
Address [1] 277104 0
Flinders Drive Bedford Park SA 5042
Country [1] 277104 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288154 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 288154 0
Level 3, Hanson Institute, RAH, North Terrace, Adelaide SA 5000
Ethics committee country [1] 288154 0
Australia
Date submitted for ethics approval [1] 288154 0
24/10/2012
Approval date [1] 288154 0
27/11/2012
Ethics approval number [1] 288154 0

Summary
Brief summary
Background: Studies have shown that antidepressants may reduce inflammation in animal models of colitis. The present trial aims to examine whether fluoxetine added to standard therapy for Crohn’s disease (CD) maintains remission, improves quality of life and/or mental health in humans with CD as compared to placebo.
Methods / Design: A parallel randomised double-blind placebo controlled trial was conducted. Participants with clinically established CD, in remission or with only mild symptoms, were randomly assigned to receive either fluoxetine 20mg daily or placebo, and followed for 12 months. Participants provided blood and stool samples and answered questionnaires measuring mental health and quality of life. Linear mixed-effects models were used to compare groups on the outcome variables.
Results: Of the 26 randomised participants, 14 were randomised to receive placebo and 12 to receive fluoxetine for 12 months. Overall, 14 (53.8%) participants were male. The mean age was 37.4 (13.2) years. Fluoxetine had no effect on IBD activity measured using the CDAI (F(3, 27.5) =.064, p=.978) or the calprotectin (F(3, 32.5)= 1.08, p=.371) during the 12-month period of observation. Similarly, there was no impact of fluoxetine on physical (p=.645), psychological (p=.884), social (p=.649), or environmental quality of life (QoL) (p=.992), on anxiety (p=.979) or depressive symptoms (p=.956) as compared to placebo.
Conclusion: 20mg of fluoxetine daily does not appear to improve the course of CD, QoL or mental health over 12 months of observation as compared to placebo. The trial documents the difficulty of conducting antidepressant trials with human subjects suffering from CD .
Trial website
Trial related presentations / publications
Not yet available
Public notes

Contacts
Principal investigator
Name 34781 0
Dr Antonina Mikocka-Walus
Address 34781 0
School of Nursing and Midwifery University of South Australia GPO Box 2471 Adelaide 5001, SA
Country 34781 0
Australia
Phone 34781 0
+61 8 83022468
Fax 34781 0
Email 34781 0
antonina.mikocka-walus@unisa.edu.au
Contact person for public queries
Name 18028 0
Dr Antonina Mikocka-Walus
Address 18028 0
School of Nursing and Midwifery
University of South Australia
GPO Box 2471
Adelaide 5001, SA
Country 18028 0
Australia
Phone 18028 0
+61 8 83022468
Fax 18028 0
+61 8 83022168
Email 18028 0
antonina.mikocka-walus@unisa.edu.au
Contact person for scientific queries
Name 8956 0
Dr Antonina Mikocka-Walus
Address 8956 0
School of Nursing and Midwifery
University of South Australia
GPO Box 2471
Adelaide 5001, SA
Country 8956 0
Australia
Phone 8956 0
+61 8 83022468
Fax 8956 0
+61 8 83022168
Email 8956 0
antonina.mikocka-walus@unisa.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary