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Trial registered on ANZCTR


Registration number
ACTRN12615001131549
Ethics application status
Approved
Date submitted
13/10/2015
Date registered
27/10/2015
Date last updated
29/09/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Gastrointestinal Hypomotility Study: Studying how Intestinal Transit is affected by Clozapine
Scientific title
An observational study: How does clozapine affect gastrointestinal transit (including gastric emptying and small and large bowel transit) as measured by wireless motility capsule in clozapine-treated inpatients in a rehabilitation service compared with normative transit times.
Secondary ID [1] 287645 0
None
Universal Trial Number (UTN)
U1111-1175-4923
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
clozapine-induced gastrointestinal hypomotility 296475 0
Condition category
Condition code
Oral and Gastrointestinal 296728 296728 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Mental Health 296729 296729 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 exposure is clozapine treatment. The condition observed is gastrointestinal transit times (gastric emptying, small bowel transit, colon transit) as measured by wireless motility capsule (WMC). After fasting overnight, the participant consumes a small standardised meal (Smartbar) then ingests a wireless motility capsule (Smartpill) which is equipped with temperature, pH, and pressure monitoring devices. The participant wears a recording device. They do not eat over the next 6 hours to capture gastric emptying times. They then eat and drink as normally. Bowel motions are noted by the participant pressing an event button on the data recorder. The WMC will transit through the gastrointestinal tract relaying data telemetrically to the recorder. The WMC ends up being expelled in the faeces and is single use only. The data receiver will be worn for 96 hours post capsule ingestion. At t=96 we will check the data output to confirm whether the WMC has been expelled. If it is still recording, the participant will wear it for a further three days. The study will be terminated at t=168 hours
Intervention code [1] 293043 0
Diagnosis / Prognosis
Comparator / control treatment
No control group - transit times from the clozapine treated group will be compared with standardised population normative gastric emptying and small and large bowel transit times
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296346 0
Gastric emptying time of clozapine-treated patients as determined by WMC (compared with population normative values). Results will be considered statistically significant at p<0.05
Timepoint [1] 296346 0
From the time of WMC ingestion to the time the WMC enters the small intestine.
Primary outcome [2] 296347 0
Small bowel transit time of clozapine-treated patients as determined by WMC (compared with population normative values). Results will be considered statistically significant at p<0.05
Timepoint [2] 296347 0
From the time the WMC enters the small intestine until the WMC enters the large intestine.
Primary outcome [3] 296348 0
Large bowel transit times of clozapine-treated patients as determined by WMC (compared with population normative values). Results will be considered statistically significant at p<0.05
Timepoint [3] 296348 0
From the time the WMC enters the large intestine until the time it is expelled.
Secondary outcome [1] 318222 0
Subjective symptoms of constipation as assessed by Modified ROME III constipation criteria
Timepoint [1] 318222 0
Day 5 of Wireless Motility capsule test

Eligibility
Key inclusion criteria
Competent and consenting adult (>18) patients prescribed clozapine (any dose) residing in a specific New Zealand low-secure mixed rehabilitation facility
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Not competent to consent
Participant takes laxatives and prefers to continue taking them during study period or their treating team has concerns about them having a laxative holiday (laxatives would cause spurious transit times)
Insulin dependent diabetics
History of:
(a) GI surgery in the last 3 months
(b) Crohn’s disease or diverticulitis
(c) implanted electromechanical device (i.e a cardiac pacing device or cochlear implant)
(d) gastric bezoar
(e) swallowing disorder
(f) suspected or known stricture or fistula
(g) physiological/ mechanical GI obstruction

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Downloaded data will be analysed using the display software (MotiliGI, SmartPill Corporation).
The WMC software generates an automated report including regional transit, and the data will be manually read and interpreted by senior gastroenterologist. When there is disagreement between automated and manual reporting a third opinion will be sought from an independent expert.
Capsule ingestion will be identified from a sudden rise in temperature profile.
Gastric emptying time (GET) will be identified as the time from ingestion of the WMC to the abrupt pH rise when the WMC leaves the acidic environment of the stomach for the alkaline duodenum. This rise will normally be >3 pH units, but will be less marked for participants on proton pump inhibitors or H2 antagonists (approx 1 pH unit).
Small bowel transit time (SBTT) is defined as the time from capsule ingestion until the abrupt pH drop (>1 pH unit), observed at least 30 min after GET and persisting for a minimum of 10 min, signifying entry into the caecum.
Body exit time is identified as an acute temperature drop when the ambient temperature, rather than body temperature, is sensed.
Colonic transit time (CTT) is defined as the time from the pH-defined entry of the WMC to the caecum until the temperature-defined body exit time.

The primary outcome variables are the various gastrointestinal transit times. Descriptive statistics (means with SDs, and plotted distributions of transit times) will provide data summaries for transit times. The estimated mean transit time will be compared with normative population data (using confidence intervals for the mean transit time). Comparison of subjective measures of constipation (using the purpose designed screening tool adapted from the Rome III criteria) will be compared between using the chi-squared test or Fisher's exact test (for comparison of categorical outcomes.) Linear regression will be used to examine the relationship between the outcome variable and other covariates such as age, gender, ethnicity and medication dose.

For colonic transit times, a-priori power analysis were conducted using data from a previous study measuring colonic transit times in clozapine-treated participants. In this previous research, clozapine treated participants had transit times four times longer that that of controls (Every-Palmer et al 2015, in progress). Mean colonic transit times in controls were 24.06 hours (CI 16.8-31.3) and in clozapine-treated participants were 100.6 hours (CI 82.1-119). At alpha=0.05 and beta =0.8, fewer than 6 participants are required to adequately power the study to detect this degree of difference in colonic transit times.

No previous research has looked at gastric or small bowel emptying in clozapine treated participants. However, if transit times were increased by a factor of 0.5, (e.g with normal GETs around 3.4 hours , +/- 1.5 hours (SD) increasing to 5.1hours in clozapine-treated participants) then at least 14 participants would be required to detect this degree of difference at alpha 0.05 and beta 0.8.

The target sample size is 20, to account for up to a 30% drop out rate.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
15/10/2015
Date of last participant enrolment
Anticipated
10/04/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment outside Australia
Country [1] 7219 0
New Zealand
State/province [1] 7219 0

Funding & Sponsors
Funding source category [1] 292208 0
Charities/Societies/Foundations
Name [1] 292208 0
Maurice and Phyllis Paykel Trust
Country [1] 292208 0
New Zealand
Funding source category [2] 292209 0
Charities/Societies/Foundations
Name [2] 292209 0
Wellington Medical Research Foundation
Country [2] 292209 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] 290882 0
Individual
Name [1] 290882 0
Professor Peter Ellis
Address [1] 290882 0
Department of Psychological Medicine, University of Otago, Wellington
PO Box 7343
Wellington 6242
Country [1] 290882 0
New Zealand
Other collaborator category [1] 278655 0
Individual
Name [1] 278655 0
Dr Stephen Inns
Address [1] 278655 0
Department of Medicine University of Otago, Wellington PO Box 7343
Newtown, Wellington
6242
Country [1] 278655 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293678 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 293678 0
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 293678 0
New Zealand
Date submitted for ethics approval [1] 293678 0
03/08/2015
Approval date [1] 293678 0
01/09/2015
Ethics approval number [1] 293678 0
15/CEN/114

Summary
Brief summary
Gastrointestinal hypomotility ("slow gut") caused by clozapine is common, important and poorly understood. It causes distress and even sudden death. It may affect more than half of clozapine treated patients, but there are no clinically reliable signs and symptoms to identify it. One in 500 clozapine treated patients die from drug­induced bowel obstruction.
Segmental gastrointestinal transit times (e.g. gastric and small bowel emptying) of clozapine treated patients have never been quantified.
This is an extension of a previous study which used radiopaque markers to explore gastrointestinal transit time in clozapine treated patients. These results showed very abnormal bowel function, but data were crude and limited to the colon. This study involves similar methodology, but a more sensitive measurement technique ­-a wireless motility capsule­ -which will provide more data and add to the understanding of this problem.
Wireless motility capsules ('smartpills') are vitamin-­pill sized capsules. When swallowed they offer an ambulatory, safe, minimally invasive and validated assessment of intraluminal pH, temperature, and pressure during their transit through the gastrointestinal (GI) tract. There is no radiation exposure to the patient. This technology allows for accurate measurement of transit times in multiple regions of the upper and lower GI tract. benefit them individually, as well as informing the evidence base.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60930 0
Dr Susanna Every-Palmer
Address 60930 0
Department of Psychological Medicine, University of Otago, Wellington
PO Box 7343
Wellington 6242
Country 60930 0
New Zealand
Phone 60930 0
+6421767675
Fax 60930 0
Email 60930 0
susanna.every-palmer@ccdhb.org.nz
Contact person for public queries
Name 60931 0
Susanna Every-Palmer
Address 60931 0
Department of Psychological Medicine, University of Otago, Wellington
PO Box 7343
Wellington 6242
Country 60931 0
New Zealand
Phone 60931 0
+6421767675
Fax 60931 0
Email 60931 0
susanna.every-palmer@ccdhb.org.nz
Contact person for scientific queries
Name 60932 0
Susanna Every-Palmer
Address 60932 0
Department of Psychological Medicine, University of Otago, Wellington
PO Box 7343
Wellington 6242
Country 60932 0
New Zealand
Phone 60932 0
+6421767675
Fax 60932 0
Email 60932 0
susanna.every-palmer@ccdhb.org.nz

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23396Study protocol  susanna.every-palmer@ccdhb.org.nz
23397Clinical study reportEvery-Palmer, S., Inns, S.J., Grant, E. et al. CNS Drugs (2019) 33: 81. https://doi.org/10.1007/s40263-018-0587-4  

Results publications and other study-related documents

Documents added manually
Current Study Results
No documents have been uploaded by study researchers.

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
4575Study results articleYes Every-Palmer, S., Inns, S.J., Grant, E. et al. CNS... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffects of Clozapine on the Gut: Cross-Sectional Study of Delayed Gastric Emptying and Small and Large Intestinal Dysmotility.2019https://dx.doi.org/10.1007/s40263-018-0587-4
N.B. These documents automatically identified may not have been verified by the study sponsor.