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Trial registered on ANZCTR


Registration number
ACTRN12623001277639
Ethics application status
Approved
Date submitted
3/10/2023
Date registered
7/12/2023
Date last updated
26/05/2024
Date data sharing statement initially provided
7/12/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of REducing cardiometabolic risk with SEmaglutide in Type 1 diabetes
Scientific title
Evaluating the efficacy of REducing cardiometabolic risk with SEmaglutide by measuring arterial stiffness in overweight and obese adults aged over 25 with Type 1 diabetes
Secondary ID [1] 310665 0
None
Universal Trial Number (UTN)
U1111-1289-8469
Trial acronym
RESET1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
type 1 diabetes 331567 0
Condition category
Condition code
Metabolic and Endocrine 328302 328302 0 0
Diabetes
Cardiovascular 328303 328303 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subcutaneous injection semaglutide, self-administered according to the following dose titration schedule: 0.25mg weekly for 4 weeks, 0.5mg weekly for 4 weeks, then 1mg weekly (or maximum tolerated dose).

Total duration post initiation of treatment 26 weeks (18 weeks at 1mg or maximum tolerated dose).
Intervention code [1] 327071 0
Treatment: Drugs
Comparator / control treatment
placebo subcutaneous injection (0.9% sodium chloride) with matching titration schedule, placebo injections appear identical to semaglutide injections

Sub-study:
an additional group without diabetes will be recruited for baseline studies of carotid femoral pulse wave velocity, pancreatic and gut hormones only, to form a comparison group to those with type 1 diabetes at baseline for these measures.
Control group
Placebo

Outcomes
Primary outcome [1] 336152 0
Change in arterial stiffness
Timepoint [1] 336152 0
baseline, 13 weeks and 26 weeks post initiation of treatment (primary endpoint), 12 weeks post cessation of treatment
Secondary outcome [1] 427099 0
Change in arterial stiffness
Timepoint [1] 427099 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [2] 427100 0
Change in heart rate
Timepoint [2] 427100 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [3] 427101 0
Change in blood pressure
Timepoint [3] 427101 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [4] 427102 0
Change in weight
Timepoint [4] 427102 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [5] 427104 0
Change in waist circumference
Timepoint [5] 427104 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [6] 427105 0
Change in waist:hip ratio
Timepoint [6] 427105 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [7] 427106 0
Change in insulin sensitivity
Timepoint [7] 427106 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [8] 427107 0
Change in fasting free fatty acid profile
Timepoint [8] 427107 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [9] 427108 0
Change in fasting lipid profile
Timepoint [9] 427108 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [10] 427109 0
Change in vascular inflammation
Timepoint [10] 427109 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [11] 427113 0
Change in adiponectin
Timepoint [11] 427113 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [12] 427123 0
Change in high sensitivity C-reactive protein (hsCRP)
Timepoint [12] 427123 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [13] 427127 0
Change in growth differentiation factor 15 (GDF-15)
Timepoint [13] 427127 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [14] 427128 0
Change in energy expenditure
Timepoint [14] 427128 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [15] 427130 0
Change in hepatic steatosis
Timepoint [15] 427130 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [16] 427132 0
Change in visceral adipose tissue
Timepoint [16] 427132 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [17] 427133 0
Change in total fat mass
Timepoint [17] 427133 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [18] 427134 0
Change in fat free mass
Timepoint [18] 427134 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [19] 427135 0
Change in % time in range
Timepoint [19] 427135 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [20] 427136 0
Change in % time in tighter range
Timepoint [20] 427136 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [21] 427137 0
Change in % time below range
Timepoint [21] 427137 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [22] 427138 0
Change in % time above range
Timepoint [22] 427138 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [23] 427139 0
Change in time below 3.0 mmol/L
Timepoint [23] 427139 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [24] 427141 0
Change in HbA1c
Timepoint [24] 427141 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [25] 427142 0
Change in total daily insulin dose
Timepoint [25] 427142 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [26] 427143 0
Change in basal insulin dose
Timepoint [26] 427143 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [27] 427144 0
Change in bolus insulin dose
Timepoint [27] 427144 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [28] 427251 0
Change in glycaemic variability
Timepoint [28] 427251 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [29] 427252 0
Change in C peptide
Timepoint [29] 427252 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [30] 427253 0
Change in glucagon
Timepoint [30] 427253 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [31] 427277 0
Mean 24-hour glucose
Timepoint [31] 427277 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [32] 427278 0
Mean overnight glucose
Timepoint [32] 427278 0
Baseline and 26 weeks post initiation of treatment
Secondary outcome [33] 427279 0
Mean daytime glucose
Timepoint [33] 427279 0
Baseline and 26 weeks post initiation of treatment

Eligibility
Key inclusion criteria
Main study:
1. type 1 diabetes of greater than or equal to 2 years duration
2. body mass index greater than or equal to 25 kg/m2
3. HbA1c greater than or equal to 7.0%
4. at least one cardiovascular risk factor:
- history of microalbuminuria [urinary albumin:creatinine ratio greater than 2.5 mg/mmol for males, greater than 3.5 mg/mmol for females]
- hypertension [Blood pressure (BP) greater than 140/90mmHg] or anti-hypertensive treatment
- hyperlipidemia [Total Cholesterol(TC):High Density Lipoprotein (HDL) ratio greater than 6] or lipid lowering therapy
- current smoking

Sub-study (Pancreatic hormones and carotid femoral pulse wave velocity only in people without diabetes to provide comparative data for baseline measures in type 1 diabetes group):
1. body mass index greater than or equal to 25 kg/m2
Minimum age
25 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Main and sub-study:
1. treatment with a GLP1 receptor agonist, metformin or SGLT2 inhibitor in the last 3 months
2. current or planned treatment with medications that affect glucose metabolism (i.e. glucocorticoids, antipsychotics, immunosuppressants)
3. previous or planned bariatric surgery during study period
4. diabetic ketoacidosis or severe hypoglycaemia in the last 12 months
5. eGFR less than 45 ml/min/1.73m2
6. evidence of significant liver disease (known cirrhosis, LFTs greater than 3x upper limit of normal)
7. known gastroparesis
8. history of pancreatitis or cholecystitis
9. pregnant, breastfeeding or female of childbearing potential not using adequate contraception
10. coronary event or stroke in the last 3 months
11. active or untreated proliferative diabetic retinopathy
12. personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
13. previous adverse reaction to semaglutide necessitating discontinuation

Sub-study:
1. diabetes mellitus

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)
Allocation performed by a physician not involved in the study and communicated to the dispensing pharmacy
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Dynamic random allocation using minimisation
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
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
5/02/2024
Actual
12/03/2024
Date of last participant enrolment
Anticipated
5/01/2026
Actual
Date of last data collection
Anticipated
29/06/2026
Actual
Sample size
Target
76
Accrual to date
7
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 314883 0
Charities/Societies/Foundations
Name [1] 314883 0
Diabetes Australia Research Trust
Country [1] 314883 0
Australia
Funding source category [2] 314911 0
Charities/Societies/Foundations
Name [2] 314911 0
Garvan Research Foundation
Country [2] 314911 0
Australia
Primary sponsor type
Other
Name
Garvan Institute of Medical Research
Address
384 Victoria St Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 316896 0
None
Name [1] 316896 0
Address [1] 316896 0
Country [1] 316896 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313881 0
St Vincent's Hospital Sydney Human Research Ethics Committee
Ethics committee address [1] 313881 0
Ethics committee country [1] 313881 0
Australia
Date submitted for ethics approval [1] 313881 0
28/11/2022
Approval date [1] 313881 0
02/02/2023
Ethics approval number [1] 313881 0

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

Contacts
Principal investigator
Name 129654 0
Prof Jerry Greenfield
Address 129654 0
Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst NSW 2010
Country 129654 0
Australia
Phone 129654 0
+61 2 8382 2622
Fax 129654 0
Email 129654 0
j.greenfield@garvan.org.au
Contact person for public queries
Name 129655 0
Ruth Frampton
Address 129655 0
Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst NSW 2010
Country 129655 0
Australia
Phone 129655 0
+61 0491 731 769
Fax 129655 0
Email 129655 0
RESET1@garvan.org.au
Contact person for scientific queries
Name 129656 0
Ruth Frampton
Address 129656 0
Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst NSW 2010
Country 129656 0
Australia
Phone 129656 0
+61 0491 731 769
Fax 129656 0
Email 129656 0
RESET1@garvan.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All individual participant data collected during the trial, after de-identification.
When will data be available (start and end dates)?
Immediately following publication (ending 5 years following main results publication).
Available to whom?
On a case-by-case basis at the discretion of the primary sponsor and pending ethics committee approval, investigators whose proposed use of the data has been approved by an independent review committee (“learned intermediary”) identified for this purpose.
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Access subject to approvals by the Principal Investigator (Professor Jerry Greenfield). Enquiries should be directed to j.greenfield@garvan.org.au


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.