ANZCTR - Registration

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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]

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.

Condition category

Condition code

Oral and Gastrointestinal

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]

Treatment: Other

Comparator / control treatment

Different doses of plant extracts and acarbose

Control group

Dose comparison

Outcomes

Primary outcome [1]

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]

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]

Starch

Timepoint [1]

Same as the primary time point

Secondary outcome [2]

Disaccharides (eg. maltose, sucrose)

Timepoint [2]

Same as the primary time point

Secondary outcome [3]

GSE

Timepoint [3]

Same as the primary time point

Secondary outcome [4]

Quercetin

Timepoint [4]

Same as the primary time point

Secondary outcome [5]

Visual analogue scales (VAS) – Nausea, bloating and abdominal cramps

Timepoint [5]

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?

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

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Ministry of Business, Innovation, and Employment (MBIE)

Address [1]

Wellington office
Level 3, 33 Bowen Street.

PO Box 5762
Wellington 6145

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern A Health and Disability Ethics Committee

Ethics committee address [1]

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]

New Zealand

Date submitted for ethics approval [1]

Approval date [1]

15/11/2013

Ethics approval number [1]

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]

/AnzctrAttachments/366087-Protocol for ANZTCR.docx

Attachments [2]

/AnzctrAttachments/366087-HDEC Letter -13NTA207- Approved Application.pdf

Attachments [3]

/AnzctrAttachments/366087-Investigator_CV_SallyPoppitt_V1_18June2013 uploaded.docx

Attachments [4]

/AnzctrAttachments/366087-Evidence of peer review and Locality forms.pdf

Attachments [5]

/AnzctrAttachments/366087-PIS and consent form v2 uploaded.docx

Contacts

Principal investigator

Name

Prof Sally D Poppitt

Address

Human Nutrition Unit University of Auckland 18 Carrick Place My Eden Auckland 1024

Country

New Zealand

Phone

+64 9 630 5160

Fax

[email protected]

Contact person for public queries

Name

Hyun Sang Shin

Address

Human Nutrition Unit University of Auckland 18 Carrick Place My Eden Auckland 1024

Country

New Zealand

Phone

+64 9 630 5160

Fax

[email protected]

Contact person for scientific queries

Name

Hyun Sang Shin

Address

Human Nutrition Unit University of Auckland 18 Carrick Place My Eden Auckland 1024

Country

New Zealand

Phone

+64 9 630 5160

Fax

[email protected]

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

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically