Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000615785
Ethics application status
Approved
Date submitted
14/04/2022
Date registered
26/04/2022
Date last updated
23/05/2022
Date data sharing statement initially provided
26/04/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A prospective study on post-meal low blood sugar levels following weight loss surgery.
Scientific title
A prospective study on reactive hypoglycaemia following bariatric surgery.
Secondary ID [1] 306775 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post bariatric hypoglycaemia 325786 0
Roux-en-Y gastric bypass 325788 0
One anastomosis gastric bypass 325789 0
Post-prandial hypotension 326059 0
Condition category
Condition code
Metabolic and Endocrine 323125 323125 0 0
Other endocrine disorders
Surgery 323126 323126 0 0
Other surgery

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Participants will have undergo a gastric emptying study (via scintigraphy) and evaluation of glucoregulatory hormones pre-surgery, 6 and 12 months post bariatric surgery.

Prior to the 6 and 12 months post-bariatric surgery study:
Five days prior to the 6 and 12 months post-surgery study, participants will be connected to a blinded, external continuous blood glucose monitor (Dexcom G6) by a study investigator. The continuous blood glucose monitoring data will be collected on the study day.

At each study:
Participants will be given a solid meal consisting of 50 g beef patty (584 kJ) that has been radiolabelled with 20 MBq of technetium-99m sulphur colloid and a 150 ml glucose drink (50 g of glucose, 840 kJ) containing 7 MBq 67Ga-EDTA and 5 g 3-O-methylglucose (3-O-MG, Sigma Aldrich USA). The meal will be administered by a trained medical professional and will be consumed over 5 minutes at the research facility. The consumption of the meal will be supervised by the medical professional and the end of the meal will be designated t = 0. Following this, gastric emptying data will be acquired by scintigraphy in 1-min frames for the first 60 minutes, followed by 3-minute frames until t = 240 minutes. A region-of-interest that corresponds to the gastric pouch will be drawn to derive emptying curves and a cobalt marker will be placed over the skin in the region of the right iliac fossa of the participant to assist with the detection of the caecum. Data will be corrected for subject movement, radionuclide decay and at t = 300 min, the participant will drink 100 ml of water labelled with 4 MBq of technetium-99m sulphur colloid and a lateral image of the stomach will be acquired to derive correction factors for gamma ray attenuation. During the study, glucoregulatory hormones will be evaluated by venous blood samples taken prior to consumption of the meal and at t= 15, 30, 60, 90, 120, 180, 240 min.

The overall duration of each study will be 5 hours.
Intervention code [1] 323228 0
Diagnosis / Prognosis
Comparator / control treatment
The outcomes of participants who have undergone a Roux-en-Y gastric bypass (RYGB) and a one anastomosis gastric bypass (OAGB) will be compared. The RYGB cohort will be the reference comparator.
Control group
Active

Outcomes
Primary outcome [1] 331086 0
Peak plasma concentration of glucagon-like peptide-1 (GLP-1) measured pre-surgery and at the 6 month post-surgery follow up.
Timepoint [1] 331086 0
Plasma GLP-1 will be measured immediately before the test meal and at t = 15, 30, 60, 90, 120, 180, 240 min post test meal completion at the pre-surgery and the 6 month post-surgery follow up study.
Secondary outcome [1] 408695 0
Time for 50% of the solid meal to empty from the gastric pouch assessed using gamma camera images (scintigraphy) following consumption of a solid meal containing 20 MBq of technetium-99m sulphur colloid.
Timepoint [1] 408695 0
Gastric pouch emptying image data will be acquired every minute for the first 60 minutes post solid/liquid meal and then every 3 minutes until 240 min post solid/liquid meal at the pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [2] 408696 0
Time for 50% of the liquid meal to empty from the gastric pouch assessed using gamma camera images (scintigraphy) following consumption of a glucose drink containing 7 MBq of gallium-67 EDTA
Timepoint [2] 408696 0
Gastric pouch emptying image data will be acquired every minute for the first 60 minutes post solid/liquid meal and then every 3 minutes until 240 min post solid/liquid meal at the pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [3] 408697 0
Plasma glucose-dependent insulinotropic polypeptide (GIP) concentrations
Timepoint [3] 408697 0
Immediately before the test meal and at t = 15, 30, 60, 90, 120, 180, 240 min post test meal completion at the pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [4] 408699 0
Plasma glucose concentrations
Timepoint [4] 408699 0
Immediately before the test meal and at t = 15, 30, 60, 90, 120, 180, 240 min post test meal completion at the pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [5] 408701 0
Peak plasma concentration of GLP-1 measured pre-surgery and at the 12 month follow up.
Timepoint [5] 408701 0
Plasma GLP-1 will be measured immediately before the test meal and at t = 15, 30, 60, 90, 120, 180, 240 min post test meal completion at the 12 months post-surgery follow up study.
Secondary outcome [6] 408702 0
Plasma insulin concentrations
Timepoint [6] 408702 0
Immediately before the test meal and at t = 15, 30, 60, 90, 120, 180, 240 min post test meal completion at the pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [7] 408703 0
Plasma C-peptide concentrations
Timepoint [7] 408703 0
Immediately before the test meal and at t = 15, 30, 60, 90, 120, 180, 240 min post test meal completion at the pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [8] 408704 0
Plasma cortisol concentrations
Timepoint [8] 408704 0
Immediately before the test meal and at t = 15, 30, 60, 90, 120, 180, 240 min post test meal completion at the pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [9] 408705 0
Plasma glucagon concentrations
Timepoint [9] 408705 0
Immediately before the test meal and at t = 15, 30, 60, 90, 120, 180, 240 min post test meal completion at the pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [10] 408706 0
Plasma adrenaline concentrations
Timepoint [10] 408706 0
Immediately before the test meal and at t = 15, 30, 60, 90, 120, 180, 240 min post test meal completion at the pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [11] 408707 0
Plasma normetanephrine concentrations
Timepoint [11] 408707 0
Immediately before the test meal and at t = 15, 30, 60, 90, 120, 180, 240 min post test meal completion at the pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [12] 408708 0
Plasma 3-OMG concentrations
Timepoint [12] 408708 0
Measured at t = 30, 60, 120, 240 min post test meal completion at the pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [13] 408709 0
Symptoms of hypoglycaemia evaluated using a scaled questionnaire.
Reference: Jones TW, Porter P, Sherwin RS, Davis EA, O'Leary P, Frazer F, Byrne G, Stick S, Tamborlane W 1998. Decreased epinephrine responses to hypoglycemia during sleep. N Engl J Med 338:1657-1662.
Timepoint [13] 408709 0
Immediately before the test meal and at t = 0, 15, 30, 60, 90, 120, 150, 180, 210 and 240 min post test meal completion at pre-surgery, 6 months and 12 months post-surgery studies.
Secondary outcome [14] 408710 0
Glycated haemoglobin (HbA1c) from whole blood samples
Timepoint [14] 408710 0
Pre-surgery, at 6 months and 12 months post-surgery follow up
Secondary outcome [15] 408711 0
Clarke hypoglycaemia score
Timepoint [15] 408711 0
At pre-surgery, 6 month and 12 month post-surgery follow up
Secondary outcome [16] 408712 0
Quality of life assessed using the SF-36 questionnaire
Timepoint [16] 408712 0
At pre-surgery, 6 month and 12 month post-surgery follow up
Secondary outcome [17] 408713 0
Diagnosis of post bariatric hypoglycaemia.
A case of post bariatric hypoglycaemia will be defined if any one of the following criteria are met:
1. Plasma glucose concentration <3.0 mmol/L within 5 hours after ingestion of test meal
2. Episode of severe hypoglycaemia at any time following bariatric surgery determined by review of patient medical records
3. Blind continuous blood glucose monitoring where participants had a glycaemic level <3.0 mmol/L with symptoms consistent with hypoglycaemia that resolved following correction of hypoglycaemia assessed by data-linkage to the Dexcom G6 App
Timepoint [17] 408713 0
At 6 and 12 months post-surgery follow up
Secondary outcome [18] 408714 0
Blood pressure measured using a sphygmomanometer
Timepoint [18] 408714 0
Measured immediately before test meal and then at 5 minute intervals until t = 120 min post test meal then 15 minute intervals until t = 240 min post test meal at the pre-surgery, 6 months and 12 months post-surgery studies
Secondary outcome [19] 408715 0
Heart rate measured using a pulse oximeter
Timepoint [19] 408715 0
Measured immediately before test meal and then at 5 minute intervals until t = 120 min post test meal then 15 minute intervals until t = 240 min post test meal at the pre-surgery, 6 months and 12 months post-surgery studies

Eligibility
Key inclusion criteria
Males and females with or without diabetes who are planned to have Roux-en-Y gastric bypass or one anastomosis gastric bypass.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Use of any medication that may influence gastrointestinal motor function, body weight or appetite (glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, opiates, anticholinergics, levodopa, clonidine, nitrates, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, prucalopride, or erythromycin)
• Evidence of drug abuse, consumption of more than 20 g alcohol per day or an active smoking history
• History of chronic gastrointestinal disease (inflammatory bowel disease, coeliac disease) or prior gastrointestinal surgery (other than other than bariatric surgery, uncomplicated appendicectomy or cholecystectomy)
• History of epilepsy
• History of severe respiratory, cardiovascular, hepatic and/or renal disease
• Impaired renal (as assessed by calculated creatinine clearance < 90 mL/min), iron status, or liver function tests outside the following ranges:
-Alanine aminotransferase (ALT) >3x ULN
-Aspartate transaminase (AST) >3x ULN
-Alkaline phosphatase (ALP) >3x ULN
-Bilirubin >24 mmol/L
-Ferritin <15 ng/mL (Females), <30 ng/mL (Males)
-Haemoglobin <115 g/L (Females), <130 g/L (Males)
• Donation of blood within the previous 3 months
• Participation in any other research studies within the previous 3 months that requires blood sampling or exposure to radiation
• Inability to give informed consent
• Female participants who are pregnant or planning for pregnancy, or are lactating
• Vegetarian

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
In a prior study (Tharakan et al.), participants with post-prandial hypoglycaemia following RYGB had a peak GLP-1 concentration of 246 (SD 15.3) pmol/L and participants without post-prandial hypoglycaemia had a peak GLP-1 concentration of 137.3 (SD 23.4) pmol/L. Accordingly, to detect this clinically significant change in peak GLP-1 concentration and accounting for a 20% drop-off rate, 15 participants from each group will be recruited.

Data will be analysed, in general, using repeated measures ANOVA. Serial measurements will be summarised by AUC. All outcomes are quantitative. The analysis will be supervised by a professional biostatistician.

Reference: Tharakan G, Behary P, Albrechtsen NJW, Chahal H, Kenkre J, Miras AD, et al. Roles of increased glycaemic variability, GLP-1 and glucagon in hypoglycaemia after Roux-en-Y gastric bypass. European Journal of Endocrinology. 2017;177(6):455-64

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
13/06/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 22202 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 37360 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 311112 0
Government body
Name [1] 311112 0
National Health and Medical Research Council
Country [1] 311112 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
Adelaide Health and Medical Science Building
4 North Terrace
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 312445 0
None
Name [1] 312445 0
None
Address [1] 312445 0
Country [1] 312445 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310962 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 310962 0
Ethics committee country [1] 310962 0
Australia
Date submitted for ethics approval [1] 310962 0
23/11/2021
Approval date [1] 310962 0
09/05/2022
Ethics approval number [1] 310962 0
2021/HRE00416

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118370 0
Prof Michael Horowitz
Address 118370 0
Level 5 Adelaide Health and Medical Science Building
4 North Terrace
Adelaide SA 5000
Country 118370 0
Australia
Phone 118370 0
+61 870742673
Fax 118370 0
Email 118370 0
[email protected]
Contact person for public queries
Name 118371 0
Ryan Jalleh
Address 118371 0
Level 5 Adelaide Health and Medical Science Building
4 North Terrace
Adelaide SA 5000
Country 118371 0
Australia
Phone 118371 0
+61 883131393
Fax 118371 0
Email 118371 0
[email protected]
Contact person for scientific queries
Name 118372 0
Ryan Jalleh
Address 118372 0
Level 5 Adelaide Health and Medical Science Building
4 North Terrace
Adelaide SA 5000
Country 118372 0
Australia
Phone 118372 0
+61 883131393
Fax 118372 0
Email 118372 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.