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Trial registered on ANZCTR


Registration number
ACTRN12625000080426
Ethics application status
Approved
Date submitted
11/12/2024
Date registered
24/01/2025
Date last updated
24/01/2025
Date data sharing statement initially provided
24/01/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of the diabetes medication, Ozempic, to reduce blood pressure falls after a meal in older people
Scientific title
Establishing the potential of the long-acting GLP-1 receptor agonist, semaglutide, as a treatment for postprandial hypotension (PPH) in older people – SAGE-PPH.
Secondary ID [1] 295188 0
None
Universal Trial Number (UTN)
Trial acronym
SAGE-PPH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postprandial hypotension 308323 0
Condition category
Condition code
Cardiovascular 307322 307322 0 0
Other cardiovascular diseases
Metabolic and Endocrine 307323 307323 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Semaglutide 0.25-1mg or matching placebo once weekly subcutaneously for 12 weeks. Semaglutide will be uptitrated from 0.25mg for 4 weeks, followed by 0.5mg for 4 weeks and then 1mg for 4 weeks. All weekly injections will be administered by a member of the study team to guarantee adherence to the study medication. The team member will be unblinded to the treatment and not involved in any aspect of the data acquisition.

A gastric emptying study using the gold standard technique (scintigraphy) will be performed by a qualified nuclear medicine technologist, at baseline (ie before treatment), at 12 weeks after commencing semaglutide. Following an overnight fast (14h solids, 12h liquids), participants will consume a 75g glucose drink (300ml) radiolabelled with 20 MBq 99mTc-DTPA to measure gastric emptying using scintigraphy. Fasting requirements will be confirmed prior to administration of the test drink.
Intervention code [1] 301527 0
Treatment: Drugs
Comparator / control treatment
Control group will receive placebo of 0.9% saline in the same volume and frequency as the treatment group, given via subcutaneous injection
Control group
Placebo

Outcomes
Primary outcome [1] 306283 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on postprandial blood pressure (BP) using an automated device (DINAMAP).
Timepoint [1] 306283 0
Blood pressure (BP) will be assessed at baseline (before trial medication) and 12 weeks after trial medication.

On each study day, participants will be allowed a period of 15 min to rest and 3 consecutive BP measurements (spaced at 3-min intervals i.e. t=-9, -6, -3 min) will be taken prior to ingestion of a 75g glucose drink made up to 300ml with water. BP will be subsequently recorded at 5 min intervals until 120 min. The primary outcome [1] measure will be the maximum fall in systolic BP after the glucose drink.
Primary outcome [2] 306285 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on postprandial heart rate (HR) using an automated device (DINAMAP).
Timepoint [2] 306285 0
Heart rate (HR) will be assessed at baseline (before trial medication) and 12 weeks after trial medication.

On each study day, participants will be allowed a period of 15 min to rest and 3 consecutive HR measurements (spaced at 3-min intervals i.e. t=-9, -6, -3 min) will be taken prior to ingestion of a 75g glucose drink made up to 300ml with water. HR will be subsequently recorded at 5 min intervals until 120 min.

The primary outcome [2] measure will be the AUC0-120min.
Secondary outcome [1] 348071 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on gastric emptying of a standardised 75g glucose drink using scintigraphy.
Timepoint [1] 348071 0
Gastric emptying will be assessed at baseline (before trial medication) and 12 weeks after trial medication.

On the day prior to each study visit, participants will be required to eat a standardised meal (McCain's frozen lasagne) with water only in the evening at approximately 7 pm, then fast overnight (14 hours for solids and 12 hours for liquids) for a baseline gastric emptying measurement. Participants will and asked to drink a standardised drink containing 75g glucose made up to 300 ml water and radiolabelled with 20 MBq 99mTc-DTPA Time zero (t=0) will be taken as the time when the participant finishes the test drink.

Gastric emptying data will be acquired in 1-min frames for the first 60 minutes followed by 3-minute frames until t=120 minutes. On one occasion, at t=120 minutes, the
volunteer will drink 100 ml of water labelled with 4MBq of 99mTc-DTPA and a lateral image of the stomach will be acquired to derive correction factors for gamma ray attenuation.

The outcome measure will be the AUC0-120min.
Secondary outcome [2] 348072 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on splanchnic blood flow as assessed with Doppler ultrasound.
Timepoint [2] 348072 0
Splanchnic blood flow will be assessed at baseline (before trial medication) and 12 weeks after trial medication.

Splanchnic blood flow will be assessed using Doppler ultrasound. Blood flow will be measured immediately before the study drink is consumed (t = -5 minutes) and then at t = 15, 30, 45, 60, 90, and 120 minutes using a Logiq e ultrasound system with a 3.5 C broad spectrum 2.5 – 4 MHz convex linear array transducer (GE Healthcare Technologies, Sydney, NSW, Australia).

Th outcome measure will be Auc0-120min.
Secondary outcome [3] 348073 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on plasma glucose using a YSI machine.
Timepoint [3] 348073 0
Plasma glucose will be assessed at baseline (before trial medication) and 12 weeks after trial medication.

Venous blood (0.5ml) will be sampled after the test drink at t = 30, 60, 90, 120 min, where t=0 represents the end of drink ingestion. Blood glucose concentrations will be measured immediately using a glucose oxidase analyser (Yellow Springs Institute, USA).

The outcome measures will be AUC0-120.
Secondary outcome [4] 348074 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on sensations of appetite using a widely used validated 100mm visual analogue scale questionnaire (Sepple CP, Read NW. Gastrointestinal correlates of the development of hunger in man. Appetite. 1989 Dec;13(3):183-91. doi: 10.1016/0195-6663(89)90011-1. PMID: 2596841.)
Timepoint [4] 348074 0
Appetite ratings will be assessed at baseline (before trial medication) and 12 weeks after trial medication.

At the same intervals used for blood sampling, subjects will complete standardised visual analogue questionnaires to score appetite ratings ie sensations of hunger, fullness, desire to eat (t = 30, 60, 90, 120 min).

The outcome measures will be AUC0-120min.
Secondary outcome [5] 348077 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on energy intake at a buffet meal as assessed using Foodworks nutrition analysis software..
Timepoint [5] 348077 0
Energy intake at a buffet meal will be assessed at baseline (before trial medication) and 12 weeks after trial medication.

At t = 120 minutes after ingestion of the radiolablelled glucose drink, 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 (Foodworks 3.01, Xyris Software, Highgate Hill, QLD, Australia).

The outcome measure will be total energy (kcal) consumed at the buffet meal.
Secondary outcome [6] 348078 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on body weight using electronic scales.
Timepoint [6] 348078 0
Body weight will be assessed at baseline (before trial medication) and 12 weeks after trial medication.

On arrival for each visit, the participant will be weighed (days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77 and 84).

The outcome measure will be the change in body weight from day 0 to 12 weeks after trial medication.
Secondary outcome [7] 348079 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on gastrointestinal symptoms using a standardised, validated PAGI-SYM questionnaire.
Timepoint [7] 348079 0
Gastrointestinal symptoms will be assessed at the screening visit (before trial medication) and 12 weeks after trial medication.

Gastrointestinal symptoms will be assessed at the screening visit using a validated PAGI-SYM questionnaire and again after 12 weeks trial medication.

The outcome measure is the change in total symptom score from 0-12 weeks.
Secondary outcome [8] 443457 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on plasma insulin using enzyme-linked immunosorbent assay (ELISA).
Timepoint [8] 443457 0
Plasma insulin will be assessed at baseline (before trial medication) and 12 weeks after trial medication.
Secondary outcome [9] 443458 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on plasma C-peptide using enzyme-linked immunosorbent assay (ELISA).
Timepoint [9] 443458 0
Plasma C-peptide will be assessed at baseline (before trial medication) and 12 weeks after trial medication.
Secondary outcome [10] 443459 0
To compare the effect of 12 weeks treatment with semaglutide QW (once weekly) versus placebo on plasma glucagon using radioimmunoassay.
Timepoint [10] 443459 0
Plasma glucagon will be assessed at baseline (before trial medication) and 12 weeks after trial medication.

Eligibility
Key inclusion criteria
• Male or female participants aged 65 – 80 years
• Body mass index (BMI) 25 – 40 kg/m2
• Haemoglobin and ferritin in the normal range for gender and age.
• Participant has provided written informed consent
Minimum age
65 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Evidence of renal disease (i.e. a creatinine clearance cut-off of < 50 ml/min. Calculated creatinine clearance will be determined as follows using the Cockcroft-Gault equation: Cr clearance = [140 - age (years) x weight (kg)] / [0.814 x serum creatinine (µmol/L)] (For female subjects, multiply Cr clearance x 0.85)(11)
• Diagnosed with Diabetes type 1 or 2 or glycated haemoglobin (HbA1c) >/= 7mmol/L
• Iron stores, or liver function tests outside the following ranges:
Alanine aminotransferase (ALT) < 55 U/L
Alkaline phosphatase (ALP) 30 - 110 U/L
Aspartate transaminase (AST) < 45 U/L
Total bilirubin 6 - 24 µmol/L
Haemoglobin 115 – 155 g/L (Females)
135 – 172 g/L (Males)
Ferritin 15 – 200 µg/L (Females)
30 – 300 µg/L (Males)
• Hepatic or cardiovascular disease, pancreatitis (subjects with past history of acute or chronic pancreatitis, gastric surgery, or known gastroparesis on history or screening biochemistry tests.
• Participants with any history of cancer, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy = 12 months prior to screening or other malignancies treated with apparent success with curative therapy = 5 years prior to screening will be excluded.
• History of any clinically significant disease or disorder which may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer’s ability to participate in the study.
• Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• History of hyperthyroidism or uncontrolled hypothyroidism.
• Chronic gastrointestinal symptoms as assessed by questionnaire.
• Use of drugs potentially affecting gastrointestinal motility (corticosteroids; anti-emetics (dopamine antagonists, 5HT-3 receptor antagonists), laxatives, prokinetic agents, anticholinergic agents, cholinergic agents, opioid medications, erythromycin).
• Current use of anticoagulants.
• Inability to abstain from smoking for 12 hours prior to the gastric emptying tests.
• Consumption of >2 units alcohol daily on a regular basis.
• Known or suspected history of alcohol or drug abuse, as judged by the Investigator.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to semaglutide or drugs with a similar chemical structure or its components.
• Baseline systolic blood pressure (SBP) < /= 100mmHg
• Participation in any research studies involving exposure to ionising radiation exceeding 3.5mSv in the previous 12 months
• Donated blood in the past 3 months

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)
Randomisation will be carried out by the Pharmacy at the Royal Adelaide Hospital (RAH). Allocation will involve contacting the holder of the allocation schedule (RAH Pharmacy) who is at a separate site to provide the medication (so that this is blinded to both the participant and study investigator).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequence generation will be carried out by the Pharmacy at the Royal Adelaide Hospital using simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The two analysis sets include the ‘intervention’ group and the ‘control/placebo’ group. Analysis will be undertaken on a per-protocol basis. Analysis of covariance (ANCOVA) will be used to compare changes in BP, HR, gastric emptying, gut hormones, appetite, energy intake, splanchnic blood flow, gastrointestinal symptoms in each group at 12 weeks, adjusting for baseline values. Secondary endpoints will be analysed in similar fashion, using ANCOVA and mixed models. The data will be analysed in consultation with a biostatistician.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
27/01/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 299774 0
Charities/Societies/Foundations
Name [1] 299774 0
The Hospital Research Foundation
Country [1] 299774 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
NHMRC Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Level 5 Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA 5005
Country
Australia
Secondary sponsor category [1] 299121 0
None
Name [1] 299121 0
Address [1] 299121 0
Country [1] 299121 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300665 0
CALHN Human Research Ethics Committee
Ethics committee address [1] 300665 0
Level 3, Roma Mitchell House 136 North Terrace Adelaide, South Australia, 5000
Ethics committee country [1] 300665 0
Australia
Date submitted for ethics approval [1] 300665 0
18/08/2024
Approval date [1] 300665 0
11/12/2024
Ethics approval number [1] 300665 0
2024/HRE00219

Summary
Brief summary
Falls in blood pressure after a meal (called postprandial hypotension) occurs commonly in people over the age of 65 years and currently has no suitable treatment.

The study will determine the effects of 12 weeks treatment with the 'long-acting' glucagon-like peptide-1 (GLP-1) agonist, semaglutide once weekly (QW), also known as Ozempic, on the rate of stomach emptying, glycaemia, blood pressure (BP) and heart rate (HR) following ingestion of a glucose drink, in people over the age of 65 years who experience postprandial hypotension. This is a randomised parallel designed study. Subjects recruited into the study who pass screening criteria will be randomised to receive semaglutide QW or matching placebo. They will have a gastric emptying study performed using the gold standard technique (scintigraphy) at baseline and 12 weeks. Immediately following the first gastric emptying study they will commence treatment with semaglutide QW or Placebo, administered subcutaneously at weekly intervals. Blood pressure, heart rate, splanchnic blood flow, appetite sensations, blood glucose and gut hormones will be assessed during each of the gastric emptying measurements. Food intake for 30 min at a buffet meal will be assessed immediately following the gastric emptying study ie ~120-150 min after the gastric emptying studies.

This study will help determine if semaglutide (Ozempic) can be useful in treating postprandial hypotension.

We hypothesise that semaglutide (Ozempic) will slow the rate of gastric emptying and, hence, reduce the magnitude of the fall in BP after ingesting a glucose drink.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84394 0
Prof Karen Jones
Address 84394 0
Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Level 5 Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA 5005, Australia
Country 84394 0
Australia
Phone 84394 0
+61 8 83137821
Fax 84394 0
Email 84394 0
[email protected]
Contact person for public queries
Name 84395 0
Karen Jones
Address 84395 0
Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Level 5 Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA 5005, Australia
Country 84395 0
Australia
Phone 84395 0
+61 8 83137821
Fax 84395 0
Email 84395 0
[email protected]
Contact person for scientific queries
Name 84396 0
Karen Jones
Address 84396 0
Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Level 5 Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA 5005, Australia
Country 84396 0
Australia
Phone 84396 0
+61 8 8313 7821
Fax 84396 0
Email 84396 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

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No documents have been uploaded by study researchers.

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No additional documents have been identified.