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Trial registered on ANZCTR


Registration number
ACTRN12624000111572
Ethics application status
Approved
Date submitted
23/12/2023
Date registered
8/02/2024
Date last updated
22/07/2024
Date data sharing statement initially provided
8/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Tirzepatide in Type 1 Diabetes: Cardiometabolic Effects
(TIRTLE)
Scientific title
Assessing the cardiometabolic effects of tirzepatide in people with type 1 diabetes
Secondary ID [1] 311091 0
None
Universal Trial Number (UTN)
U1111-1301-2135
Trial acronym
TIRTLE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes 332244 0
Condition category
Condition code
Metabolic and Endocrine 328959 328959 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
subcutaneous tirzepatide injection 2.5mg once weekly for 4 weeks, then 5.0mg once weekly (or maximum tolerated dose) for 12 weeks post initiation of treatment
Intervention code [1] 327541 0
Treatment: Drugs
Comparator / control treatment
Placebo subcutaneous injection with matching titration schedule. Placebo injections are given as saline.
Control group
Placebo

Outcomes
Primary outcome [1] 336753 0
Weight (kg)
Timepoint [1] 336753 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [1] 429572 0
Arterial stiffness
Timepoint [1] 429572 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [2] 429573 0
Heart rate
Timepoint [2] 429573 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [3] 429574 0
Blood pressure
Timepoint [3] 429574 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [4] 429575 0
waist:hip ratio
Timepoint [4] 429575 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [5] 429576 0
Fasting free fatty acids
Timepoint [5] 429576 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [6] 429577 0
Fasting lipid profile
Timepoint [6] 429577 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [7] 429578 0
Vascular inflammation
Timepoint [7] 429578 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [8] 429579 0
high-sensitivity c-reactive protein
Timepoint [8] 429579 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [9] 429580 0
liver function tests
Timepoint [9] 429580 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [10] 429581 0
energy expenditure (fasting)
Timepoint [10] 429581 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [11] 429584 0
total fat mass
Timepoint [11] 429584 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment t
Secondary outcome [12] 429585 0
fat free mass
Timepoint [12] 429585 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [13] 429586 0
time in range (3.9-10mmol/L)
Timepoint [13] 429586 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [14] 429587 0
glycaemic variability (coefficient of variation)
Timepoint [14] 429587 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [15] 429588 0
time below range (<3.9mmol/L, <3.0mmol/L)
Timepoint [15] 429588 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [16] 429589 0
time above range (>10mmol/L, 13.9mmol/L)
Timepoint [16] 429589 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [17] 429590 0
mean glucose over 24 hours (mmol/L)
Timepoint [17] 429590 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [18] 429591 0
mean overnight glucose (mmol/L between midnight to 0600AM)
Timepoint [18] 429591 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [19] 429592 0
mean daytime glucose (0600AM to midnight)
Timepoint [19] 429592 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [20] 429593 0
HbA1c
Timepoint [20] 429593 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [21] 429594 0
total daily insulin dose (units)
Timepoint [21] 429594 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [22] 429595 0
basal insulin dose (units)
Timepoint [22] 429595 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [23] 429596 0
bolus insulin dose
Timepoint [23] 429596 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [24] 429597 0
fasting c-peptide
Timepoint [24] 429597 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [25] 429598 0
fasting glucagon
Timepoint [25] 429598 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [26] 430824 0
Arterial stiffness
Timepoint [26] 430824 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [27] 437741 0
Total body water
Timepoint [27] 437741 0
Secondary outcome [28] 437742 0
Total body water
Timepoint [28] 437742 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [29] 437743 0
Diet patterns
Timepoint [29] 437743 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [30] 437744 0
Diet patterns
Timepoint [30] 437744 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [31] 437745 0
Eating behaviour
Timepoint [31] 437745 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [32] 437746 0
Eating behaviour
Timepoint [32] 437746 0
Change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [33] 437747 0
Gastrointestinal symptoms
Timepoint [33] 437747 0
Change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [34] 437748 0
Gastrointestinal symptoms
Timepoint [34] 437748 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [35] 437749 0
Fasting GLP1 (glucagon-like peptide 1)
Timepoint [35] 437749 0
change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment
Secondary outcome [36] 437750 0
Fasting GLP1 (glucagon-like peptide 1)
Timepoint [36] 437750 0
Change from baseline (taken prior to commencement of treatment) and after 12 weeks post commencement of treatment

Eligibility
Key inclusion criteria
• age 18-60 years
• 2 years since diagnosis of type 1 diabetes
• BMI greater than or equal to 30 kg/m2
• Willingness to give written informed consent, participate and comply with the study.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• treatment with a glucagon-like peptide-1 (GLP1) receptor agonist, or a sodium-glucose cotransporter 2 (SGLT2) inhibitor in the last 6 weeks
• treatment with glucocorticoids in the last 6 weeks
• previous bariatric surgery or planned during the trial period
• diabetic ketoacidosis or severe hypoglycaemia in the last 3 months
• eGFR <45 ml/min/1.73m2
• evidence of significant liver disease (known cirrhosis, LFTs > 3x upper limit of normal)
• known gastroparesis
• history of pancreatitis or cholecystitis
• pregnant, breastfeeding or female of childbearing potential not using adequate contraception
• coronary event or stroke in the last 3 months
• history of active proliferative diabetic retinopathy or macular oedema
• cognitive impairment or significant psychiatric illness which impairs ability to understand study requirements

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
14/05/2024
Actual
14/05/2024
Date of last participant enrolment
Anticipated
1/08/2024
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
24
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 315350 0
Charities/Societies/Foundations
Name [1] 315350 0
Philanothropic donations to Garvan Institute of Medical Research
Country [1] 315350 0
Australia
Primary sponsor type
Other
Name
Garvan Institute of Medical Research
Address
384 Victoria St Darlinghurst
Country
Australia
Secondary sponsor category [1] 317411 0
None
Name [1] 317411 0
Address [1] 317411 0
Country [1] 317411 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314269 0
St Vincent's Hospital Human Research Ethics Committee (HREC)
Ethics committee address [1] 314269 0
97-105 Boundary Street Darlinghurst NSW 2010
Ethics committee country [1] 314269 0
Australia
Date submitted for ethics approval [1] 314269 0
Approval date [1] 314269 0
01/12/2023
Ethics approval number [1] 314269 0

Summary
Brief summary
Cardiovascular disease and its risk factors are prominent issues in T1D. There is a need to identify therapies that can address weight, glycaemia and other cardiometabolic indices in T1D. In T1D, whether tirzepatide, a dual gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist improves weight, glycaemia and cardiometabolic health has not been previously studied. The TIRTLE study is a randomised controlled clinical trial in adults with type 1 diabetes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130998 0
Dr Jennifer Snaith
Address 130998 0
Garvan Institute of Medical Research, 384 Victoria St Darlinghurst NSW 2010
Country 130998 0
Australia
Phone 130998 0
+61491731769
Fax 130998 0
Email 130998 0
[email protected]
Contact person for public queries
Name 130999 0
Ruth Frampton
Address 130999 0
Garvan Institute of Medical Research, 384 Victoria St Darlinghurst NSW 2010
Country 130999 0
Australia
Phone 130999 0
+61491731769
Fax 130999 0
Email 130999 0
[email protected]
Contact person for scientific queries
Name 131000 0
Jerry Greenfield
Address 131000 0
Garvan Institute of Medical Research, 384 Victoria St Darlinghurst NSW 2010
Country 131000 0
Australia
Phone 131000 0
+61 02 9295 8100
Fax 131000 0
Email 131000 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.