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Trial registered on ANZCTR


Registration number
ACTRN12624000534583
Ethics application status
Approved
Date submitted
19/03/2024
Date registered
30/04/2024
Date last updated
30/04/2024
Date data sharing statement initially provided
30/04/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Evaluating the effects of the gut hormone, glucose-dependent insulinotropic polypeptide (GIP) on stomach emptying, blood pressure, gut blood flow and blood sugar levels in healthy older subjects
Scientific title
Effects of exogenous and endogenous glucose-dependent insulinotropic polypeptide on gastric emptying, blood pressure, splanchnic blood flow and glycaemia in healthy older subjects
Secondary ID [1] 311777 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
postprandial hypotension 333283 0
Condition category
Condition code
Cardiovascular 329975 329975 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will be studied on 3 separate occasions, separated by an intervals of at least 7 days. Participants will be given an intravenous (iv) injection of GIP (1.5 pmol/kg/min), GIP antagonist (800 pmol/kg/min) or 0.9% saline (placebo) at approximately 9.00am (t = -30 min). Thirty minutes after the iv dose, the participant will be given a drink (t = 0 min) comprising 75g glucose and 5g 3-Ortho-Methyl-glucose labelled with 20 MBq 99mTc-calcium phytate, made up to 300ml water. 3-OMG is a non-metabolisable glucose analogue and plasma levels can be used to assess glucose absorption. Gastric emptying, plasma glucose, plasma insulin, blood pressure (BP), heart rate (HR), superior mesenteric artery (SMA) flow and appetite will be monitored for 180 minutes after ingestion of the drink. At t = 180 min, the participants will be presented with a cold, buffet-style meal and be allowed 30 minutes to freely consume food until they are comfortably full. The weight of the food will be recorded before and after it is offered to the subjects and energy intake and macronutrient composition calculated subsequently using commercially available software.

At least one member of the research team will be present at all times to monitor participants and to ensure adherence to the intervention.
Intervention code [1] 328229 0
Treatment: Drugs
Comparator / control treatment
Intravenous infusion of 0.9% saline
Control group
Placebo

Outcomes
Primary outcome [1] 337737 0
To evaluate the effect of the change in systolic blood pressure (BP) after placebo compared to the GIP antagonist and GIP in healthy older people
Timepoint [1] 337737 0
On study days, BP will be measured immediately prior to administration of the study drug (GIP, GIP antagonist or placebo) (t = -33 minutes) and at 3 minute intervals until just prior to ingestion of the drink (ie t = -3 minutes) and then at 5 minute intervals from t = 0 - 180 minutes, using an automated BP device. Measurements will also be taken at -39, -36, -33 minutes prior to administration of study drug (or saline) and the average taken to represent ‘baseline’.
Secondary outcome [1] 433047 0
Area under the systolic BP curve 0-120 min between placebo and the GIP antagonist and GIP
Timepoint [1] 433047 0
On study days, BP will be measured immediately prior to administration of the study drug (GIP, GIP antagonist or placebo) (t = -33 minutes) and at 3 minute intervals until just prior to ingestion of the drink (ie t = -3 minutes) and then at 5 minute intervals from t = 0 - 180 minutes, using an automated BP device. Measurements will also be taken at -39, -36, -33 minutes prior to administration of study drug (or saline) and the average taken to represent ‘baseline’.
Secondary outcome [2] 433049 0
Area under the diastolic BP curve 0-120 min between placebo and the GIP antagonist and GIP
Timepoint [2] 433049 0
On study days, BP and HR will be measured immediately prior to administration of the study drug (GIP, GIP antagonist or placebo) (t = -33 minutes) and at 3 minute intervals until just prior to ingestion of the drink (ie t = -3 minutes) and then at 5 minute intervals from t = 0 - 180 minutes, using an automated BP device. Measurements will also be taken at -39, -36, -33 minutes prior to administration of study drug (or saline) and the average taken to represent ‘baseline’.
Secondary outcome [3] 433050 0
Area under the HR curve 0-120 min between placebo and the GIP antagonist and GIP
Timepoint [3] 433050 0
On study days, HR will be measured immediately prior to administration of the study drug (GIP, GIP antagonist or placebo) (t = -33 minutes) and at 3 minute intervals until just prior to ingestion of the drink (ie t = -3 minutes) and then at 5 minute intervals from t = 0 - 180 minutes, using an automated BP device. Measurements will also be taken at -39, -36, -33 minutes prior to administration of study drug (or saline) and the average taken to represent ‘baseline’.
Secondary outcome [4] 433051 0
Area under the gastric emptying curve 0-180 min between placebo and the GIP antagonist and GIP
Timepoint [4] 433051 0
Gastric emptying will be assessed immediately after drink ingestion (t=0 minutes) in dynamic mode i.e. in 1 min frames for the first 60 minutes and in 3-minute frames thereafter until t=180 minutes.
Secondary outcome [5] 433053 0
Area under the blood glucose curve 0-180 min between placebo and the GIP antagonist and GIP
Timepoint [5] 433053 0
Blood samples (12 ml) will be obtained prior to administration of study drug (t = -33 minutes), 15 minutes into the administration of the study drug (t = -15 minutes), just prior to the ingestion of the drink (ie t = -3 minutes) and then at t = 0, 5, 15, 30, 45, 60, 90, 120, 150 and 180 minutes for measurement of plasma glucose.
Secondary outcome [6] 433054 0
Area under the oral glucose absorption curve 0-180 min between placebo and the GIP antagonist and GIP
Timepoint [6] 433054 0
Blood samples (5 ml) will be collected at t = 5, 15, 30, 60, 90, 120, 150 and 180 minutes for measurement of serum 3-OMG as a measure of oral glucose absorption.
Secondary outcome [7] 433055 0
Area under the SMA blood flow curve 0-180 min between placebo and the GIP antagonist and GIP
Timepoint [7] 433055 0
SMA blood flow will be assessed using a Logiq-9 GE ultrasound system.. SMA blood flow will be measured immediately prior to injection of GIP, GIP antagonist or placebo (t = -33 minutes) and ingestion of the drink (t = -3 minutes) then every 15 minutes until t = 180 minutes.
Secondary outcome [8] 433057 0
Area under the plasma c-peptide curve 0-180 min between placebo and the GIP antagonist and GIP
Timepoint [8] 433057 0
Blood samples (12 ml) will be obtained prior to administration of study drug (t = -33 minutes), 15 minutes into the administration of the study drug (t = -15 minutes), just prior to the ingestion of the drink (ie t = -3 minutes) and then at t = 0, 5, 15, 30, 45, 60, 90, 120, 150 and 180 minutes for measurement of c-peptide.
Secondary outcome [9] 433058 0
Area under the plasma insulin curve 0-180 min between placebo and the GIP antagonist and GIP
Timepoint [9] 433058 0
Blood samples (12 ml) will be obtained prior to administration of study drug (t = -33 minutes), 15 minutes into the administration of the study drug (t = -15 minutes), just prior to the ingestion of the drink (ie t = -3 minutes) and then at t = 0, 5, 15, 30, 45, 60, 90, 120, 150 and 180 minutes for measurement of plasma insulin.
Secondary outcome [10] 433059 0
Area under the plasma GLP-1 curve 0-180 min between placebo and the GIP antagonist and GIP
Timepoint [10] 433059 0
Blood samples (12 ml) will be obtained prior to administration of study drug (t = -33 minutes), 15 minutes into the administration of the study drug (t = -15 minutes), just prior to the ingestion of the drink (ie t = -3 minutes) and then at t = 0, 5, 15, 30, 45, 60, 90, 120, 150 and 180 minutes for measurement of plasma GLP-1.
Secondary outcome [11] 433060 0
Area under the plasma glucagon curve 0-180 min between placebo and the GIP antagonist and GIP
Timepoint [11] 433060 0
Blood samples (12 ml) will be obtained prior to administration of study drug (t = -33 minutes), 15 minutes into the administration of the study drug (t = -15 minutes), just prior to the ingestion of the drink (ie t = -3 minutes) and then at t = 0, 5, 15, 30, 45, 60, 90, 120, 150 and 180 minutes for measurement of plasma glucagon.
Secondary outcome [12] 433061 0
Area under the plasma GIP curve 0-180 min between placebo and the GIP antagonist and GIP
Timepoint [12] 433061 0
Blood samples (12 ml) will be obtained prior to administration of study drug (t = -33 minutes), 15 minutes into the administration of the study drug (t = -15 minutes), just prior to the ingestion of the drink (ie t = -3 minutes) and then at t = 0, 5, 15, 30, 45, 60, 90, 120, 150 and 180 minutes for measurement of plasma GIP.
Secondary outcome [13] 433063 0
Area under the Hunger curve 0-180 min between placebo and the GIP antagonist and GIP
Timepoint [13] 433063 0
Sensations of hunger will be evaluated using a visual analogue scale immediately prior injection of GIP, GIP antagonist or placebo (t = -33 minutes) and ingestion of the drink (t = -3 minutes) then every 15 minutes until t = 180 minutes. A final visual analogue questionnaire will be administered at t=210 min after the buffet meal.
Secondary outcome [14] 433064 0
Area under the Fullness curve 0-180 min between placebo and the GIP antagonist and GIP
Timepoint [14] 433064 0
Sensations of fullness will be evaluated using a visual analogue scale immediately prior injection of GIP, GIP antagonist or placebo (t = -33 minutes) and ingestion of the drink (t = -3 minutes) then every 15 minutes until t = 180 minutes. A final visual analogue questionnaire will be administered at t=210 min after the buffet meal.
Secondary outcome [15] 433065 0
Subsequent food intake at the buffet meal between placebo and the GIP antagonist and GIP
Timepoint [15] 433065 0
Food intake during the period t=180-210 min will be assessed.

Eligibility
Key inclusion criteria
• Male or female healthy participants
• Body Mass Index (BMI) 19 - 35 kg/m²
Minimum age
65 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Participants with diabetes, a history of severe respiratory, cardiovascular, hepatic and/or renal disease (severe in that the social or physical manifestation of the disease, or living with the condition, impact negatively and significantly on the individuals’ ability to lead a normal day to day life), chronic alcohol abuse or epilepsy (excluded by history) or if iron status, or liver function tests are outside the following ranges:
• Alanine aminotransferase (ALT) 0 - 55 U/L
• Alkaline phosphatase 30 - 110 U/L
• Aspartate transaminase 0 - 45 U/L
• Amylase and/or lipase >3 x ULN
• Bilirubin 6 - 24 mmol/L
• Ferritin 15 – 200 ng/mL (Females)
30 – 300 ng/mL (Males)
• Haemoglobin 115 - 155 g/L (Females)
135 – 172 g/L (Males)

• Participants with a creatinine clearance cut-off of < 50 ml/min
Calculated creatinine clearance will be determined as follows (29):
Cr clearance = [140 - age (years) x weight (kg)] / [0.814 x serum creatinine (µmol/L)]
(For female subjects, multiply Cr clearance x 0.85)
• Participants requiring medication likely to influence BP or gastrointestinal function
• Participants with a past history of gastrointestinal disease, including known gastroparesis, significant upper gastrointestinal symptoms and previous gastric surgery
• Participants with a history of unexplained pancreatitis, chronic pancreatitis, pancreatectomy,
• Participants with a current or prior history of c-cell carcinoma
• Smoking > 10 cigarettes/day
• Alcohol consumption > 20 g/day
• Participants who have donated blood in the previous 12 weeks

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The randomisation schedule was generated using a computer generated program. Allocation involved contacting the RAH Pharmacy of the allocation schedule who was "off-site". Study drug was provided in labelled bags for infusion that maintained blinding of the research team and study participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation sequence
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
Twenty healthy participants aged 65 - 80 years will be recruited (to allow for dropouts, which based on our experience approximates 10%). Eighteen participants are required to detect a 7mmHg decrease in the maximum fall in systolic BP after placebo compared to GIP(3-30)NH2, allowing for all possible post hoc tests between the 3 visits (power 80%, significance 5%). Data will be analysed using standardised, non-parametric or parametric statistical methods where appropriate (e.g. repeated measures Analysis of Variance (ANOVA)

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
13/02/2020
Date of last participant enrolment
Anticipated
Actual
24/11/2023
Date of last data collection
Anticipated
Actual
22/12/2023
Sample size
Target
18
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 26289 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 42260 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 316111 0
Hospital
Name [1] 316111 0
Royal Adelaide Hospital
Country [1] 316111 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
Country
Australia
Secondary sponsor category [1] 318288 0
None
Name [1] 318288 0
Address [1] 318288 0
Country [1] 318288 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314942 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 314942 0
Ethics committee country [1] 314942 0
Australia
Date submitted for ethics approval [1] 314942 0
15/05/2018
Approval date [1] 314942 0
14/02/2019
Ethics approval number [1] 314942 0
HREC/18/CALHN/320

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

Contacts
Principal investigator
Name 133194 0
Prof Karen Jones
Address 133194 0
Adelaide Medical School, The University of Adelaide, Level 5, AHMS Building, North Tce, Adelaide, SA, 5000
Country 133194 0
Australia
Phone 133194 0
+61 8 83137821
Fax 133194 0
Email 133194 0
karen.jones@adelaide.edu.au
Contact person for public queries
Name 133195 0
Prof Karen Jones
Address 133195 0
Adelaide Medical School, The University of Adelaide, Level 5, AHMS Building, North Tce, Adelaide, SA, 5000
Country 133195 0
Australia
Phone 133195 0
+61 8 83137821
Fax 133195 0
Email 133195 0
karen.jones@adelaide.edu.au
Contact person for scientific queries
Name 133196 0
Prof Karen Jones
Address 133196 0
Adelaide Medical School, The University of Adelaide, Level 5, AHMS Building, North Tce, Adelaide, SA, 5000
Country 133196 0
Australia
Phone 133196 0
+61 8 83137821
Fax 133196 0
Email 133196 0
karen.jones@adelaide.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The ethical statement and informed consent do not allow for free data 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.