Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000382673
Ethics application status
Approved
Date submitted
31/03/2014
Date registered
9/04/2014
Date last updated
22/10/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Activation of the ileal brake by carbohydrates and plant extracts – A pilot study in ileostomy patients to develop sample collection and analytical methods
Scientific title
Activation of the ileal brake- A nutritional intervention study to assess the efficacy of a starch breakdown inhibitor and a glucose uptake inhibitor present in natural plant extracts, on the oral delivery of carbohydrates to the ileum, in a group of ileostomy patients in whom it is possible to measure glucose and other types of carbohydrates from breakfast.
Secondary ID [1] 284368 0
Nil
Universal Trial Number (UTN)
U 1111-1148-6904
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
This is a nutritional intervention study designed to assess the efficacy of a starch breakdown inhibitor and a glucose
uptake inhibitor present in natural plant extracts, on the oral delivery of carbohydrates to the ileum, in a group of ileostomy patients in whom it is possible to sample the contents of the ileum directly. 291531 0
Condition category
Condition code
Oral and Gastrointestinal 291910 291910 0 0
Normal oral and gastrointestinal development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will undertake 1 or more of the 10 treatment arms, below. A 2 MJ CHO (available mono/disaccharide; low resistant starch, RS; low non-starch polysaccharide, NSP) breakfast meal, comprised of 185 g of white toast bread will be given, accompanied by the oral ingestion of an encapsulated GSE, starch breakdown inhibitor and an encapsulated quercetin, glucose uptake blocker.
This is a pilot study in patients with direct access to the ileal contents, to determine whether CHO can be detected within the ileum by sampling GI contents directly from the ileostomy pouch
10 treatment arms will be assessed as follows:
1. 2MJ CHO breakfast, with no encapsulated extracts (negative control)
2. 2MJ CHO breakfast + Acarbose (50 mg), glucose uptake inhibitor (positive control), Oral at the same time as breakfast
3. 2MJ CHO breakfast + Acarbose (50 mg) in in gastric-resistant capsule 60 minutes prior to breakfast
4. 2MJ CHO breakfast + GSE (500 mg), low dose, Oral in gastric-resistant capsule 60 minutes prior to breakfast
5. 2MJ CHO breakfast + GSE (2000 mg), high dose, Oral in gastric-resistant capsule 60 minutes prior to breakfast
6. 2MJ CHO breakfast + GSE (500 mg), low dose, Oral in non-gastric-resistant capsule at the same tine as breakfast
7. 2MJ CHO breakfast + GSE (2000 mg), high dose, Oral in non-gastric-resistant capsule at the same tine as breakfast
8. 2MJ CHO breakfast + Quercetin, (500 mg) low dose, Oral in in gastric-resistant capsule 60 minutes prior to breakfast
9. 2MJ CHO breakfast + Quercetin, (2000 mg) high dose, Oral in gastric-resistant capsule 60 minutes prior to breakfast
10. 2MJ CHO breakfast + GSE (2000 mg)/Quercetin (2000 mg) synergy, Oral in gastric-resistant capsule 60 minutes prior to breakfast
Intervention code [1] 289097 0
Treatment: Other
Comparator / control treatment
Different doses of plant extracts and acarbose
Control group
Dose comparison

Outcomes
Primary outcome [1] 291821 0
About 10 g sample of the ileal pouch contents will be collected into ethanol and kept chilled at 4 degree Celsius, until batch analyses for glucose are conducted. 10 g sample will be sufficient for all of the outcome measurements.
Timepoint [1] 291821 0
3 hours after breakfast with one of the intervention capsules.
Ileostomy bag contents, to sample the nutrients that are delivered into the ileum, will be collected at 0, 15, 30, 45, and 60 minutes after the breakfast, and then at 5 minute intervals for the following 2 hours. If gut contents arrive at the ileum prior to 60 minutes then the 5 minute sampling regime will be brought forwards.
Secondary outcome [1] 307610 0
Starch
Timepoint [1] 307610 0
Same as the primary time point
Secondary outcome [2] 307659 0
Disaccharides (eg. maltose, sucrose)
Timepoint [2] 307659 0
Same as the primary time point
Secondary outcome [3] 307660 0
GSE
Timepoint [3] 307660 0
Same as the primary time point
Secondary outcome [4] 307661 0
Quercetin
Timepoint [4] 307661 0
Same as the primary time point
Secondary outcome [5] 307662 0
Visual analogue scales (VAS) – Nausea, bloating and abdominal cramps
Timepoint [5] 307662 0
Throughout the day at various time point. first hour after breakfast will be every 15 min, then every 30 min for the following 2 hours.
Timepoint will be at 0, 15, 30, 45, 60, 90, 120, 150, 180, and 210.

Eligibility
Key inclusion criteria
Patients who have undergone an end ileostomy procedure, where the large bowel has been removed but the small bowel remains healthy and intact
Procedure conducted more than 12 months previously, and currently stable
This may include patients with ulcerative colitis (UC)
Male or female, aged 20-79 years
BMI <40kg/m2
otherwise healthy
Minimum age
20 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who have undergone loop ileostomy
Crohn’s disease; celiac disease; diabetes mellitus (T1DM or T2DM)
Drug therapies that may alter small bowel transit, including non-steroidal inflammatory drugs (NSAIDs), antibiotics and proton pump inhibitors
Drug therapies that may interact with Acarbose (PrandaseTM, PrecoseTM)
Morbid obesity, BMI >40kg/m2
Any allergy to grape

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This is a non-randomized, qualitative, pilot study. Participants may take part in 1 or more treatments.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Participant can choose the number of visits and on each visit one of the 7 treatments will be given.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Not Applicable

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/04/2014
Actual
21/04/2014
Date of last participant enrolment
Anticipated
Actual
30/06/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
7
Accrual to date
Final
4
Recruitment outside Australia
Country [1] 5947 0
New Zealand
State/province [1] 5947 0
Auckland

Funding & Sponsors
Funding source category [1] 289008 0
Government body
Name [1] 289008 0
Ministry of Business, Innovation, and Employment (MBIE)
Country [1] 289008 0
New Zealand
Primary sponsor type
Government body
Name
Plant and Food Research Ltd
Address
120 Mt Albert Road
Sandringham
Auckland 1025
Country
New Zealand
Secondary sponsor category [1] 287687 0
None
Name [1] 287687 0
Address [1] 287687 0
Country [1] 287687 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290816 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 290816 0
Health and Disability Ethics Committees
Ministry of Health
C/- MEDSAFE, Level 6, Deloitte House
10 Brandon Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 290816 0
New Zealand
Date submitted for ethics approval [1] 290816 0
Approval date [1] 290816 0
15/11/2013
Ethics approval number [1] 290816 0
13/NTA/207

Summary
Brief summary
The gastrointestinal (GI) tract and specifically the most distal part of the small intestine, the ileum, has become a renewed focus of interest for mechanisms targeting appetite suppression. The ‘ileal brake’ is stimulated when energy-containing nutrients are delivered beyond the duodenum and jejunum and into the ileum, and is named for the feedback loop which slows or ‘brakes’ gastric emptying and duodenojejunal motility. More recently it has been hypothesised that the ileal brake also promotes secretion of satiety-enhancing GI peptides and suppresses hunger, and hence in turn places a ’brake’ on food intake. Postprandial delivery of macronutrients to the ileum, other than unavailable carbohydrates (CHO) which bypass absorption in the small intestine en route to fermentation in the large bowel, is an uncommon event and hence this brake mechanism is rarely activated following a meal.
Evidence linking the ileal brake to enhanced satiety can be found from a number of studies that have delivered nutrients to the ileum enterally. Early nasoileal (NI) tube feeding studies where lipid emulsions were infused directly into the ileum significantly decreased appetite and food intake (Welch et al., 1985; Welch et al., 1988b; Welch et al., 1988c)(Maljaars et al., 2008, 20009, 2010, 2011, 2012; see review by Shin et al., 2013). There is some preliminary evidence that commercial lipid formulations designed to resist digestion and absorption in the proximal small intestine are transported to the ileum and suppress food intake (Burns et al., 2000, 2001, 2002; Diepvens et al., 2007), although findings from these feeding studies remain mixed (Smit et al., 2011; Chan et al., 2012).
Our research group has recently shown that hunger and food intake can be altered acutely by infusion of glucose in to the ileum using an NI tube (Shin et al., unpublished data) suggesting that carbohydrates can also activate the ileal brake mechanism. However, no corresponding evidence exists for ileal brake activation following the ingestion of carbohydrate containing foods. This is likely to be due to the very efficient digestion and absorption of carbohydrates by the proximal SI resulting in minimal glucose availability in the ileum.
In order to ensure arrival of CHOs into the distal small intestine (ileum) it is necessary to induce a degree of carbohydrate malabsorption in the proximal small intestine (duodenum and jejunum). This approach has previously been demonstrated using a carbohydrate meal and pharmacological interventions such as the a-glucosidase inhibitor migitol (Lee et al., 2002; Kaku et al., 2012) or a novel glucose transport inhibitor LX4211 (Zambrowicz et al., 2013) where enhanced ratings of satiety and postprandial GLP-1 and PYY concentrations beyond 2 h have been demonstrated, indicating ileal brake activation.
A number of natural occurring plant phytochemicals have been demonstrated to posses similar carbohydrate malabsorption potential (Lakshimi et al., 2012), although their ability to trigger ileal brake activation has not as yet been demonstrated in vivo. We have recently identified in vitro, a commercially available grape seed extract (Oxifend, Registerd Trademark, grape seed extract, New Zealand Extracts Ltd) and quercetin possessing the ability to inhibit the activity of starch digestive enzymes and the absorption of glucose by the gut mucosa, respectively. By combining these extracts with a starch based meal we hope to induce enough glucose malabsorption in the proximal SI to activate the ileal brake. However, efficacy of these blockers singularly or in combination has not yet been assessed in a human study population.
Trial website
Trial related presentations / publications
There has not been any presentation or publication relating to this trial.
Public notes
Attachments [1] 18 18 0 0
/AnzctrAttachments/366087-Protocol for ANZTCR.docx
Attachments [2] 19 19 0 0
/AnzctrAttachments/366087-HDEC Letter -13NTA207- Approved Application.pdf
Attachments [3] 22 22 0 0
/AnzctrAttachments/366087-Investigator_CV_SallyPoppitt_V1_18June2013 uploaded.docx
Attachments [4] 23 23 0 0
/AnzctrAttachments/366087-Evidence of peer review and Locality forms.pdf
Attachments [5] 24 24 0 0
/AnzctrAttachments/366087-PIS and consent form v2 uploaded.docx

Contacts
Principal investigator
Name 47406 0
Prof Sally D Poppitt
Address 47406 0
Human Nutrition Unit University of Auckland 18 Carrick Place My Eden Auckland 1024
Country 47406 0
New Zealand
Phone 47406 0
+64 9 630 5160
Fax 47406 0
Email 47406 0
s.poppitt@auckland.ac.nz
Contact person for public queries
Name 47407 0
Hyun Sang Shin
Address 47407 0
Human Nutrition Unit University of Auckland 18 Carrick Place My Eden Auckland 1024
Country 47407 0
New Zealand
Phone 47407 0
+64 9 630 5160
Fax 47407 0
Email 47407 0
h.shin@auckland.ac.nz
Contact person for scientific queries
Name 47408 0
Hyun Sang Shin
Address 47408 0
Human Nutrition Unit University of Auckland 18 Carrick Place My Eden Auckland 1024
Country 47408 0
New Zealand
Phone 47408 0
+64 9 630 5160
Fax 47408 0
Email 47408 0
h.shin@auckland.ac.nz

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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Documents added automatically
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