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Trial registered on ANZCTR


Registration number
ACTRN12616001405404
Ethics application status
Approved
Date submitted
30/09/2016
Date registered
10/10/2016
Date last updated
10/10/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Comparing gastrointestinal motility in clozapine-treated patients before and after laxative guided by the Porirua Protocol
Scientific title
Comparing gastrointestinal motility in clozapine-treated patients before and after laxative treatment guided by the Porirua Protocol
Secondary ID [1] 290243 0
Nil known
Universal Trial Number (UTN)
U1111-1188-1548
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
clozapine-induced gastrointestinal hypomotility 300449 0
Condition category
Condition code
Oral and Gastrointestinal 300305 300305 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Mental Health 300306 300306 0 0
Schizophrenia

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The condition observed is colonic transit time (as measured by radiopaque marker studies using the Metcalf technique). The exposure is laxative treatment prescribed according to the Porirua Protocol (which is attached). At the first timepoint colonic transit time was measured in the absence of the Porirua Protocol. Participants were then established on the Porirua Protocol by their clinical teams (the Protocol is treatment as usual in the service where this study takes place. The study design was observational; treatment was guided by the Protocol and determined by the clinical teams and participants, treatment was not manipulated by the researchers). After at least two months of treatment on the Protocol, colonic transit time was measured again.
Intervention code [1] 296029 0
Diagnosis / Prognosis
Comparator / control treatment
This is a pre and post treatment design with each patient acting as their own control with comparisons made before and after treatment with the Porirua Protocol. The design was chosen due to ethical considerations: a placebo control group could not be justified in a cohort with high rates of clozapine-induced gastrointestinal hypomotility.
Control group
Active

Outcomes
Primary outcome [1] 299779 0
Colonic transit time as measured by radiopaque marker studies
Timepoint [1] 299779 0
From the time the first radiopaque marker is ingested until time=72 hours (if 2/3 or more of the ROMs are expelled at t=72) or time=144 hours (if less than 2/3 of ROMs are excreted at t=72)
Secondary outcome [1] 328096 0
Subjective symptoms of constipation as assessed by modified ROME III constipation criteria
Timepoint [1] 328096 0
At 72 hours after commencing study
Secondary outcome [2] 328103 0
Self-reported constipation
Timepoint [2] 328103 0
At 72 hours after commencing study
Secondary outcome [3] 328104 0
Adverse effects using a clinician administered checklist which asks whether the participant has experienced bloating, cramping, diarrhoea, abdominal pain, nausea, increase thirst or other effect they believe to be related to the laxatives, and to describe each effect they may have experienced
Timepoint [3] 328104 0
at 72 and 144 hours after commencing study

Eligibility
Key inclusion criteria
Male and female adult patients (>18) prescribed clozapine (any dose) for at least 3 months, who are able to provide informed consent, had previously consented to baseline bowel motility testing and who have then received laxatives prescribed in accordance with the Porirua Protocol for at least two months.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients under the age of 18, unable to provide informed consent or who do not understand English.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
The primary outcome variable is colonic transit time (CTT) as measured by radiopaque marker (ROM) transit studies, reported as both continuous (CTT in hours) and categorical outcome measures (normal or abnormal test). A CTT >2SD above the population mean (i.e. >64.9 hours) was pre-specified as a positive test for colonic hypomotility. A CTT >4SD above the population mean (i.e. >101 hours) was defined as severe colonic hypomotility.

Descriptive statistics (medians with IQR, and plotted distributions of transit times) provide data summaries for transit times.

Kaplan-Meier survival analysis calculates median transit times (with 95% CI).

Differences in CTT without and with laxative treatment are compared using the Wilcoxon signed-rank test. The proportion of participants with gastrointestinal hypomotility and severe gastrointestinal hypomotility are compared between the two timepoints using McNemar’s 2-sided exact test, which takes into account the paired nature of the observations.

While CTTs displayed a skewed distribution, we also calculated means and standard deviation for comparison with population normative values.

Differences between pre- and post-treatment groups were considered statistically significant when p<0.05.

No similar studies had been conducted, making power calculations speculative. At alpha=0.05 and beta=0.8, a sample size of 20 (the target sample size) is adequately powered to detect a difference between two dependent means (pre and post treatment transit times) of >10 hours (SD=15). It A priori it was possible this study may have been underpowered to detect a true difference, but was intended to inform any future studies.

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 outside Australia
Country [1] 8279 0
New Zealand
State/province [1] 8279 0
Wellington

Funding & Sponsors
Funding source category [1] 294610 0
Hospital
Name [1] 294610 0
Capital and Coast District Health Board Small Research Grant
Address [1] 294610 0
Capital and Coast District Health Board, Private Bag 7902, Wellington 6021
Country [1] 294610 0
New Zealand
Primary sponsor type
Individual
Name
Susanna Every-Palmer
Address
Department of Psychological Medicine, University of Otago, Wellington
PO Box 7343
Wellington 6242
Country
New Zealand
Secondary sponsor category [1] 293474 0
Individual
Name [1] 293474 0
Professor Peter Ellis
Address [1] 293474 0
Department of Psychological Medicine, University of Otago, Wellington PO Box 7343 Wellington 6242
Country [1] 293474 0
New Zealand
Other collaborator category [1] 279239 0
Individual
Name [1] 279239 0
Mike Nowitz
Address [1] 279239 0
Department of Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242
Country [1] 279239 0
New Zealand
Other collaborator category [2] 279240 0
Individual
Name [2] 279240 0
James Stanley
Address [2] 279240 0
Department of Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242
Country [2] 279240 0
New Zealand
Other collaborator category [3] 279241 0
Individual
Name [3] 279241 0
Eve Grant
Address [3] 279241 0
Te Korowai Whariki Central Regional Forensic Service, Capital and District Health Board, PO Box 50-233, Porirua
Country [3] 279241 0
New Zealand
Other collaborator category [4] 279242 0
Individual
Name [4] 279242 0
Mark Huthwaite
Address [4] 279242 0
Department of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242
Country [4] 279242 0
New Zealand
Other collaborator category [5] 279243 0
Individual
Name [5] 279243 0
Helen Dunn
Address [5] 279243 0
Pharmacy Department, Capital and Coast District Health Board, Private Bag 7902, Wellington 6021
Country [5] 279243 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296054 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 296054 0
Ministry of Health Freyberg Building 20 Aitken Street PO Box 5013 Wellington 6011
Ethics committee country [1] 296054 0
New Zealand
Date submitted for ethics approval [1] 296054 0
Approval date [1] 296054 0
23/10/2013
Ethics approval number [1] 296054 0
13/CEN/153

Summary
Brief summary
Clozapine, an antipsychotic used in treatment-resistant schizophrenia, causes marked gastrointestinal hypomotility in 50-80% of patients. Clozapine-induced gastrointestinal hypomotility is both common and serious; it can result in severe constipation, ileus, bowel obstruction and related complications. Little evidence exists on its prevention and management. Subjective constipation has been found unreliable in predicting objective hypomotility.

In this study, using a standardized radiopaque marker (‘Metcalf’) method we compare the colonic transit times of clozapine-treated inpatients at baseline (while not receiving laxatives) with transit times when receiving laxatives, with treatment prescribed according to the Porirua Protocol (see attachment) for clozapine-related constipation (docusate & senna augmented by macrogol 3350 in treatment-resistant cases). Treatment is guided by the Protocol (which is standard treatment at the clinical site this research took place in) and not manipulated by the researchers.

Our objective was to determine in this naturalistic setting whether use of the Porirua Protocol in clozapine-treated psychiatric inpatients changed gastrointestinal motility.

Methods were specified a-priori in the protocol, published in the University of Otago Research Archive (http://hdl.handle.net/10523/6392).
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1142 1142 0 0

Contacts
Principal investigator
Name 69362 0
Dr Susanna Every-Palmer
Address 69362 0
Department of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242
Country 69362 0
New Zealand
Phone 69362 0
+6421767675
Fax 69362 0
Email 69362 0
Susanna.every-palmer@ccdhb.org.nz
Contact person for public queries
Name 69363 0
Dr Susanna Every-Palmer
Address 69363 0
Department of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242
Country 69363 0
New Zealand
Phone 69363 0
+6421767675
Fax 69363 0
Email 69363 0
Susanna.every-palmer@ccdhb.org.nz
Contact person for scientific queries
Name 69364 0
Dr Susanna Every-Palmer
Address 69364 0
Department of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242
Country 69364 0
New Zealand
Phone 69364 0
+64 21767675
Fax 69364 0
Email 69364 0
Susanna.every-palmer@ccdhb.org.nz

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