Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001369516
Ethics application status
Approved
Date submitted
25/10/2024
Date registered
18/11/2024
Date last updated
18/11/2024
Date data sharing statement initially provided
18/11/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and Efficacy of Tirzepatide ± Exercise in adults with Obesity and Type 1 Diabetes Mellitus: a pilot 3-arm open-label randomised controlled trial (TEX OB-1)
Scientific title
Safety and Efficacy of Tirzepatide ± Exercise in adults with Obesity and Type 1 Diabetes Mellitus: a pilot 3-arm open-label randomised controlled trial (TEX OB-1)
Secondary ID [1] 293887 0
None
Universal Trial Number (UTN)
Trial acronym
TEX OB-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
type 1 diabetes 335540 0
obesity 335541 0
Condition category
Condition code
Metabolic and Endocrine 332109 332109 0 0
Diabetes
Metabolic and Endocrine 332110 332110 0 0
Metabolic disorders
Physical Medicine / Rehabilitation 332184 332184 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
12 week treatment period:
• Arm 1: receive low dose tirzepatide (2.5mg subcutaneous injection weekly for 4 weeks, then 5mg subcutaneous injection weekly for 8 weeks) in addition to usual care. Tirzepatide adherence will be monitored via used vial/pen return.

• Arm 2: receive low dose tirzepatide (2.5mg subcutaneous injection weekly for 4 weeks, then 5mg subcutaneous injection weekly for 8 weeks) and participate in a tailored exercise program, in addition to usual care. Tirzepatide adherence will be monitored via used vial/pen return. Participants randomised to the tirzepatide + exercise arm will receive at least 1 x 30 to 60 mins 1:1 session with the exercise physiologist at the research clinic for an initial assessment and to receive education on how to complete a tailored exercise program at home consisting of both aerobic exercises (e.g. treadmill) and resistance exercises (e.g. resistance bands, lifting weights). Exercises performed will be tailored to the participant's capabilities and preferences. During the aerobic exercise assessment, the exercise physiologist will assess for suitable "moderate intensity" power and subsequent exercise power will be prescribed based on HR and/or RPE. A brief strength assessment will be used to dictate prescribed load. Participants will be invited to participate in further group sessions with a maximum of 12 participants (30 to 60 mins twice weekly for at least first 2 weeks of program). Adherence will be monitored via attendance records (for sessions with exercise physiologist) as well as Fitbit metrics (for home-based exercise). Participants will be advised to perform 45 to 60 mins of exercise on 3 to 6 days of the week.

• Arm 3: receive usual care. Participants will continue regular consultations with their usual endocrinologist and diabetes educator


12 week follow-up period:
• Arm 1: cease tirzepatide and continue with usual care.

• Arm 2: cease tirzepatide but continue with exercise program in addition to usual care. The exercise program will continue for a total 24 weeks (12 weeks intervention period and 12 weeks follow-up period).

• Arm 3: continue with usual care.
Intervention code [1] 329815 0
Treatment: Drugs
Intervention code [2] 329816 0
Lifestyle
Intervention code [3] 329865 0
Treatment: Other
Comparator / control treatment
Participants in Arm 3 will receive usual care. Participants will continue regular consultations with their usual endocrinologist and diabetes educator.
Control group
Active

Outcomes
Primary outcome [1] 339698 0
Change in body weight (%) as measured using digital scales
Timepoint [1] 339698 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Primary outcome [2] 339699 0
Change in % Time in Range assessed using data from continuous glucose monitoring
Timepoint [2] 339699 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [1] 440934 0
• Change in HbA1c (%) assessed using plasma assay
Timepoint [1] 440934 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [2] 440935 0
• Change in body weight (kg) assessed using digital scales
Timepoint [2] 440935 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [3] 441225 0
• Change in BMI (kg/m2) assessed using digital scales and wall height meter
Timepoint [3] 441225 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [4] 441226 0
• Proportion of patients achieving greater than or equal to 5% reduction to total body weight assessed using digital scales
Timepoint [4] 441226 0
12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [5] 441227 0
• Change in fasting glucose levels assessed using plasma assay and/or data from continuous glucose monitoring
Timepoint [5] 441227 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [6] 441228 0
• Change in % Time Below Range assessed using data from continuous glucose monitoring
Timepoint [6] 441228 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [7] 441229 0
• Change in total daily insulin dose as determined using data from insulin pumps or data on subcutaneous insulin use based on participant report
Timepoint [7] 441229 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [8] 441230 0
• Proportion of patients achieving the target value of HbA1c <7% assessed using plasma assay
Timepoint [8] 441230 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [9] 441231 0
• Change in aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and gamma-glutamyl transpeptidase levels assessed using plasma assay (composite outcome)
Timepoint [9] 441231 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [10] 441232 0
• Change in fasting total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels assessed using plasma assay (composite outcome)
Timepoint [10] 441232 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [11] 441233 0
• Change in urine albumin to creatinine ratio and protein to creatinine ratio assessed using spot urine assays (composite outcome)
Timepoint [11] 441233 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [12] 441234 0
• Change in seated systolic and diastolic blood pressure assessed using a sphygmomanometer (composite outcome)
Timepoint [12] 441234 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [13] 441235 0
• Change in waist circumference (cm) assessed using a tape measure at the midpoint between the lower border of the rib cage and the iliac crest
Timepoint [13] 441235 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [14] 441236 0
• Change in body composition measures including lean mass and fat mass assessed using DEXA and/or BOD POD (composite outcome)
Timepoint [14] 441236 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [15] 441237 0
• Change in NAFLD Fibrosis score
Timepoint [15] 441237 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [16] 441238 0
• Change in FibroScan measures of hepatic stiffness and steatosis (composite outcome)
Timepoint [16] 441238 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [17] 441239 0
• Change in arterial applanation tonometry, flow-mediated dilatation measures assessed using SphygmoCor, duplex ultrasound (composite outcome)
Timepoint [17] 441239 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [18] 441240 0
• Change in electrocardiogram measures and heart rate variability assessed using 3-lead and 12-lead electrocardiogram (composite outcome)
Timepoint [18] 441240 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [19] 441241 0
• Change in CRP and cytokines assessed using plasma assay (composite outcome)
Timepoint [19] 441241 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [20] 441242 0
• Change in diabetes distress using the Type 1 Diabetes Distress Scale (T1-DDS)
Timepoint [20] 441242 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [21] 441243 0
• Change in health-related quality of life using EQ-5D-5L
Timepoint [21] 441243 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [22] 441244 0
• Change in weight-related quality of life using IWQOL-Lite CT
Timepoint [22] 441244 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [23] 441245 0
• Change in weight, physical activity and lifestyle patterns using Weight and Lifestyle Inventory (WALI), International Physical Activity Questionnaire (IPAQ short form), and Modifiable Activity Questionnaire (MAQ) (composite outcome)
Timepoint [23] 441245 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [24] 441246 0
• Change in emotional states of depression, anxiety and stress using Depression Anxiety and Stress Scale 21 (DASS-21) (composite outcome)
Timepoint [24] 441246 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [25] 441247 0
• Change in health tracking metrics including heart rate, exercise, and sleep patterns and food logs derived from Fitbit devices with extraction and analysis via the Fitabase platform as required (composite outcome)
Timepoint [25] 441247 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [26] 441248 0
• Change in measures of cardiorespiratory fitness including VO2peak and 6 minute walk test (composite outcome)
Timepoint [26] 441248 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [27] 441249 0
• Change in measures of muscle strength including 1 repetition max test (leg press and chest press) and hand grip strength (composite outcome)
Timepoint [27] 441249 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [28] 441250 0
• Acceptability of Tirzepatide Questionnaires (designed specifically for this study)
Timepoint [28] 441250 0
12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [29] 441251 0
• Acceptability of Exercise Program Questionnaires (designed specifically for this study)
Timepoint [29] 441251 0
12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [30] 441554 0
• Change in fasting insulin and C-peptide levels (composite outcome)
Timepoint [30] 441554 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [31] 441556 0
• Change in % Time Above Range assessed using data from continuous glucose monitoring
Timepoint [31] 441556 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [32] 441557 0
• Change in Glucose Variability assessed using data from continuous glucose monitoring
Timepoint [32] 441557 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [33] 441558 0
• Change in Glucose Management Index assessed using data from continuous glucose monitoring
Timepoint [33] 441558 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial
Secondary outcome [34] 441565 0
• Change in FIB-4 Index
Timepoint [34] 441565 0
baseline, 12 weeks post-commencement in trial, 24 weeks post-commencement in trial

Eligibility
Key inclusion criteria
• men and women aged 18 to 60 years (inclusive)
• on basal bolus insulin or continuous insulin infusion via a subcutaneous insulin pump.
• able to provide informed consent according to local regulations
• documented diagnosis of type 1 diabetes mellitus (T1DM) using World Health Organization classification criteria or other local guidelines
• body mass index (BMI) greater than or equal to 30 kg/m2 (or greater than or equal to 27.5 kg/m2 in Asians and Indigenous Australians)
• HbA1c 7% to 10% (inclusive) at Visit 1.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• weight loss or weight gain of > 5% of total body weight within the past 3 months
• current use of GLP-1 RAs or anti-obesity drugs
• history of chronic pancreatitis or acute pancreatitis
• history of pancreatic malignancy
• history of pancreas surgery
• known proliferative retinopathy or diabetic maculopathy
• nonproliferative diabetic retinopathy that required acute treatment within the past 12 months
• history of ketoacidosis or hyperosmolar hyperglycaemic state within the past 12 months
• history of severe hypoglycaemia within 3 months prior to Visit 1 (defined as hypoglycaemia requiring assistance from others to treat)
• history of a clinically significant gastric emptying abnormality
• history of bariatric surgery
• chronic use of medications that directly affect gastrointestinal motility
• eGFR < 30 ml/min/1.73 m2
• acute coronary/cerebrovascular event or hospitalisation due to congestive heart failure within previous 3 months prior to enrolment
• planned coronary, carotid, or peripheral artery revascularization
• New York Heart Association (NYHA) Class III or IV Heart Failure
• any liver disease other than metabolic-associated fatty liver disease (MAFLD). Those with end-stage liver disease will be excluded.
• symptomatic gallbladder disease
• prior organ transplant (corneal transplants allowed)
• evidence of a significant and active condition that, in the opinion of the investigator, is likely to require concurrent and/or recurrent treatment with systemic glucocorticoids in the next 12 months
• receiving chronic (> 14 days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, or inhaled preparations) or have received such therapy within 1 month of Visit 1
• have evidence of a significant uncontrolled medical condition in the opinion of the investigator
• known eating disorder or disordered eating behaviours
• personal or family history of Multiple Endocrine Neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma
• personal history of non-familial medullary thyroid carcinoma
• diagnosis of malignant neoplasm in the previous 5 years (except non-metastatic basal cell skin cancer or squamous cell skin cancer)
• women of childbearing potential who are pregnant, breast-feeding, intend to become pregnant during the trial period or 3 months after the last dose of tirzepatide, or does not agree to use adequate contraceptive in the opinion of the investigators.
• unable to use CGM
• unable to test capillary glucose and ketones
• physical disability, cognitive impairment, psychiatric condition, or other reason precluding adequate understanding of, or compliance with, study procedures in the opinion of the investigator
• any other condition (e.g. known illicit drug or alcohol abuse) that in the opinion of the investigator, may preclude the patient from following and completing the protocol



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 concealment via sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/12/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 298510 0
Hospital
Name [1] 298510 0
In-kind support from the Royal Prince Alfred Hospital Diabetes Centre
Country [1] 298510 0
Australia
Primary sponsor type
Government body
Name
Sydney Local health District
Address
Country
Australia
Secondary sponsor category [1] 320051 0
None
Name [1] 320051 0
Address [1] 320051 0
Country [1] 320051 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299489 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 299489 0
Ethics committee country [1] 299489 0
Australia
Date submitted for ethics approval [1] 299489 0
Approval date [1] 299489 0
14/02/2024
Ethics approval number [1] 299489 0

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

Contacts
Principal investigator
Name 80586 0
Dr Xi May Zhen
Address 80586 0
Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, 40 Missenden Road Camperdown NSW Australia 2050
Country 80586 0
Australia
Phone 80586 0
+61 0422899893
Fax 80586 0
Email 80586 0
ximay.zhen@health.nsw.gov.au
Contact person for public queries
Name 80587 0
Xi May Zhen
Address 80587 0
Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, 40 Missenden Road Camperdown NSW Australia 2050
Country 80587 0
Australia
Phone 80587 0
+61 02 9515 5888
Fax 80587 0
Email 80587 0
ximay.zhen@health.nsw.gov.au
Contact person for scientific queries
Name 80588 0
Xi May Zhen
Address 80588 0
Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, 40 Missenden Road Camperdown NSW Australia 2050
Country 80588 0
Australia
Phone 80588 0
+61 02 9515 5888
Fax 80588 0
Email 80588 0
ximay.zhen@health.nsw.gov.au

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.