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Trial registered on ANZCTR


Registration number
ACTRN12615000518561
Ethics application status
Approved
Date submitted
7/05/2015
Date registered
25/05/2015
Date last updated
19/05/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Does gut bacterial material pass to the bloodstream of women with Crohn's disease more easily compared with healthy women?
Scientific title
Is the increase in permeability of the gut found in women with Crohn’s disease accompainied by greater absorption of bacterial endotoxin than in healthy women?
Secondary ID [1] 286632 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn's disease 294950 0
gut permeability in health and Crohn's disease 294951 0
Condition category
Condition code
Oral and Gastrointestinal 295212 295212 0 0
Crohn's disease

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
A venous blood sample from each participant will be drawn on arrival at our research facilities. Each participant will drink 100 ml of a lactulose- mannitol solution containing 10 g of lactulose and 5 g of mannitol immediately followed by 300 ml of water. Participants will be ask to to empty their bladder on arrival and at 1.5 and 3 hours after the consumption of the lactulose-mannitol solution.
Intervention code [1] 291771 0
Not applicable
Comparator / control treatment
Data obtained in subjects with Crohn's disease will be compared to that from healthy control subjects i.e. persons without any intestinal or other disorders
Control group
Active

Outcomes
Primary outcome [1] 295005 0
Comparisons of the correlation of serum endotoxin levels with permeability of the gut in healthy subjects and those with Crohn's disease. The endotoxin level will be determined using Limulus Amebocyte Lysate (LAL) assay. Gut permeability will be assessed by the excretion of lactulose and mannitol in urine.
Timepoint [1] 295005 0
Blood samples will be drawn at the commencement of the session (prior to the ingestion of the lactulose-mannitol solution) for the determination of serum endotoxin.
The excretion of lactulose and mannitol in urine are determined three hours after the ingestion of the lactulose-mannitol solution.
Primary outcome [2] 295011 0
Similarly, the comparisons of the correlation of serum LBP (Lipopolysaccharide- binding protein) with permeability of the gut in healthy subjects and those with Crohn's disease. LBP levels will be determined using an ELISA.
The excretion of lactulose and mannitol in urine are determined three hours after the ingestion of the lactulose-mannitol solution.
Timepoint [2] 295011 0
Blood samples will be drawn at the commencement of the session (prior to the ingestion of the lactulose-mannitol solution) for the determination of serum LBP.
Secondary outcome [1] 314567 0
Comparisons of the correlation of serum endotoxin level with serum LBP level in healthy subjects and those with Crohn's disease.
Timepoint [1] 314567 0
Blood sample for the determination of serum endotoxin and LBP level will be drawn at baseline (prior to the ingestion of the lactulose-mannitol solution).

Eligibility
Key inclusion criteria
for Crohn's disease group
- Diagnosis of Crohn’s disease at least 6 months prior to the study
- either being in remission or having mild and moderate disease activity as assessed by the Harvey-Bradshaw Index (HBI) (remission: HBI <5, moderate disease activity: HBI 5-8, mild disease activity: HBI 8-16)
Minimum age
20 Years
Maximum age
60 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Have any dietary excesses or particularities e.g. food allergies
- Drink more than one alcoholic standard drink per day (or more than seven alcoholic standard drinks per week)
- Are pregnant or lactating
- Are taking vitamin/ mineral supplements
- Have a history of diabetes, renal (kidney) disorders or cancer
- Have an aversion to venepuncture, difficult veins, a history of bleeding disorders or on anticoagulant therapy
- recent consumption of foods containing lactulose or mannitol

additional exclusion criteria for healthy volunteers:
- Have a medical or family history of Crohn’s disease, ulcerative colitis or irritable bowel disease
- Have a recent history of abdominal pain, nausea, vomiting, diarrhoea, passage of blood and mucus in stool

Study design
Purpose
Duration
Selection
Case control
Timing
Statistical methods / analysis
No published data are available that have concurrently determined the levels of serum endotoxin and the permeability of the gut to lactulose and mannitol in subjects with Crohn's disease and compared those with these in healthy control subjects. In a previous study we observed a significant difference of the rate of excretion of lactulose in 4 subjects with inactive Crohn's disease and 6 healthy controls. Published data indicate that the serum level of endotoxin and LBP are elevated by 35% and by 80%, respectively, in subjects with inactive CD compared to healthy controls. In the case of serum endotoxin levels a sample size of 15 subjects per group is needed to achieve a statistical power of 0.8. Hence, the recommended sample size is 45 women to distinguish between subject with mild to moderate Crohn's disease and subjects with inactive Crohn's disease and healthy control subjects.

All parameters in all samples will be determined in duplicates. The data will be checked for normal distribution. If it, or its residuals, are non-parametric distributed we will endeavor to render it parametric using the Johnson Transformation. Failing this, data will be compared by non-parametric statistical tests. Normally distributed data obtained from subjects with Crohn's disease will be compared with those obtained in healthy subjects by ANOVA. Statistical significance of difference will be considered when p < 0.05.

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] 6865 0
New Zealand
State/province [1] 6865 0

Funding & Sponsors
Funding source category [1] 291235 0
University
Name [1] 291235 0
Massey University
Address [1] 291235 0
Tennent Drive, Palmerston North 4474
Country [1] 291235 0
New Zealand
Primary sponsor type
University
Name
Massey University
Address
Tennent Drive, Palmerston North 4474
Country
New Zealand
Secondary sponsor category [1] 289910 0
None
Name [1] 289910 0
Address [1] 289910 0
Country [1] 289910 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292794 0
Massey University Human Ethics Committee Southern
Ethics committee address [1] 292794 0
Research Ethics Office
Courtyard Complex (PN221)
Massey University
Private Bag 11 222
Palmerston North 4442
Ethics committee country [1] 292794 0
New Zealand
Date submitted for ethics approval [1] 292794 0
18/03/2015
Approval date [1] 292794 0
22/04/2015
Ethics approval number [1] 292794 0
MUHEC Soutern A Application 15/18

Summary
Brief summary
The purpose of the study is to determine the permeability of the gut in health and in Crohn's disease and the concentration of bacterial endotoxin in the systemic circulation in order to assess whether a leaky gut is accompanied with greater absorption of bacterial products e.g. endotoxin.
Trial website
Trial related presentations / publications
Not applicable
Public notes

Contacts
Principal investigator
Name 56942 0
Ms Anne Gnauck
Address 56942 0
School of Food and Nutrition
Massey University
Riddet Road
Palmerston North 4474
Country 56942 0
New Zealand
Phone 56942 0
+64 (0)6 356 9099 extn. 84537
Fax 56942 0
Email 56942 0
A.Gnauck@massey.ac.nz
Contact person for public queries
Name 56943 0
Ms Anne Gnauck
Address 56943 0
School of Food and Nutrition
Massey University
Riddet Road
Palmerston North 4474
Country 56943 0
New Zealand
Phone 56943 0
+64 (0)6 356 9099 extn. 84537
Fax 56943 0
Email 56943 0
A.Gnauck@massey.ac.nz
Contact person for scientific queries
Name 56944 0
Ms Anne Gnauck
Address 56944 0
School of Food and Nutrition
Massey University
Riddet Road
Palmerston North 4474
Country 56944 0
New Zealand
Phone 56944 0
+64 (0)6 356 9099 extn. 84537
Fax 56944 0
Email 56944 0
A.Gnauck@massey.ac.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