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Trial registered on ANZCTR

Registration number

ACTRN12624000992505

Ethics application status

Approved

Date submitted

30/07/2024

Date registered

14/08/2024

Date last updated

14/08/2024

Date data sharing statement initially provided

14/08/2024

Type of registration

Prospectively registered

Titles & IDs

Public title

Evaluating Glucose Levels and Risk of Ketoacidosis in People with Type 1 Diabetes Receiving SGLT1/2 inhibitor Therapy Using a Novel Continuous Ketone Sensor; Exercise Sub-Study

Scientific title

Evaluating Glucose Levels and Risk of Ketoacidosis in People with Type 1 Diabetes Receiving SGLT1/2 inhibitor Therapy Using a Novel Continuous Ketone Sensor (PARTNER); Exercise Sub-Study

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

PARTNER sub-study

Linked study record

This record is a sub-study of ACTRN12624000448549.

Health condition

Health condition(s) or problem(s) studied:

Type 1 Diabetes

Condition category

Condition code

Metabolic and Endocrine

Diabetes

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

After screening, participants will undergo a 2-week run-in period where they will wear a continuous glucose monitor and ketone sensor and receive education about management of sustained hyperglycemia/ketosis.
After run-in, participants will be randomized to either the intervention or placebo.
The intervention will be Sotagliflozin 200 mg oral tablet daily for three months.
Adherence to intervention will be monitored by counting number of study drugs returned at the end of intervention.
1 exercise session of 40 minutes will be completed after 6-weeks of each arm, a total of two sessions one during the 12-week sotaglioflozin and one during the placebo treatment period.
The sessions will be conducted between 07:00 and 09:30 in the morning proceeding an overnight fast from the previous evening. The exercise session will be high intensity (80-90% of age predicted max heart rate) interval cardio session on a cycle ergometer. The session will entail 4 x 5min 'hard' intervals ensuring the participant is working between the prescribed heart rate limits. The participant will wear a heart rate monitor to ensure appropriate intensity and these sessions will be supervised by post-doctoral research fellows who have experience conducting clinical research exercise sessions.
Wash-out period is 2 weeks between interventions.
Arm 1: Sotagliflozin for 12 weeks, exercise session post week 6 of intervention. Then cross-over to Placebo for 12 weeks after washout
Arm 2: Placebo for 12 weeks, exercise session post week 6 of intervention. Then cross-over to Sotagliflozin for 12 weeks after washout
Session attendance will be recorded in our database and monitored by investigators to ensure adherence to exercise session requirements within the required timeframes.

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Treatment: Devices

Comparator / control treatment

The control group will be a placebo control group. The placebo tablet will contain the same excipients without the active drug, comprising of croscarmellose sodium, colloidal silicondioxide, microcrystalline cellulose, magnesium stearate, and talc.

Control group

Placebo

Outcomes

Primary outcome [1]

The primary outcome will be total % continuous ketone monitor (CKM) time spent >1.5 mmol/L from exercise onset until 24 hours post-exercise for each study arm.

Timepoint [1]

Exercise onset (T=0), to 24 hours post exercise (T=24)

Secondary outcome [1]

Glycaemic outcome A: Study continuous glucose monitor (CGM) metrics of time in range (% time in range (3.9-10.0mmol/L)) from exercise commencement (t=0) to 2hrs post-exercise (t=2)

Timepoint [1]

Beginning exercise (t=0) to 2 hrs post-exercise (t=2)

Secondary outcome [2]

Percentage time in range (3.9-10.0 mmol/L) on continuous glucose monitor from exercise commencement (t=0) to 24hrs post exercise (t=24)

Timepoint [2]

T=0 to T=24hrs post-exercise

Secondary outcome [3]

Mean glucose on continuous glucose monitor.

Timepoint [3]

Mean glucose will be monitored in the acute post-exercise period from T=0 - T=2 hrs post-exercise.

Secondary outcome [4]

Glucose management indicator on continuous glucose monitor.

Timepoint [4]

Glucose management indicator will be monitored in the acute post-exercise period from T= 0 - T=2 hrs post-exercise.

Secondary outcome [5]

Glycaemic variability on continuous glucose monitor.

Timepoint [5]

Glycaemic variability will be monitored in the acute post-exercise period from T=0 - T=2 hrs post-exercise.

Secondary outcome [6]

Percentage time above range (>13.9 mmol/L) on continuous glucose monitor.

Timepoint [6]

Percentage time above range will be monitored in the acute post-exercise period from T=0 - T=2 hrs post-exercise.

Secondary outcome [7]

Percentage time between range (10.1-13.9 mmol/L) on continuous glucose monitor.

Timepoint [7]

Percentage time between range (10.1-13.9 mmol/L) will be monitored in the acute post-exercise period from T=0 - T=2 hrs post-exercise

Secondary outcome [8]

Percentage time between range (3.0-3.8 mmol/L) on continuous glucose monitor.

Timepoint [8]

Percentage time between (3.0-3.8 mmol/L) range will be monitored in the acute post-exercise period from T=0 - T=2 hrs post-exercise

Secondary outcome [9]

Percentage time below range (<3.0 mmol/L) on continuous glucose monitor.

Timepoint [9]

Percentage time below range will be monitored in the acute post-exercise period from T=0 - T=2 hrs post-exercise.

Secondary outcome [10]

Glycaemic risk index

Timepoint [10]

Glycaemic risk index will be monitored in the acute post-exercise period from T=0 - T=2 hrs post-exercise.

Secondary outcome [11]

Percentage time ketone levels above 0.6 mmol/L

Timepoint [11]

Percentage time ketone levels above (0.6 mmol/L) will be monitored in the acute post-exercise period from T= 0 - T=2 hrs post-exercise.

Secondary outcome [12]

Percentage time ketone levels above 1.5 mmol/L

Timepoint [12]

Percentage time ketone levels above (1.5 mmol/L) will be monitored in the acute post-exercise period from T= 0 - T=2 hrs post-exercise.

Secondary outcome [13]

Percentage time ketone levels above 3.0 mmol/L

Timepoint [13]

Percentage time ketone levels above (3.0 mmol/L) will be monitored in the acute post-exercise period from T= 0 - T=2 hrs post-exercise.

Secondary outcome [14]

Rating of perceived exertion during exercise

Timepoint [14]

Every 10 mins from T=0 - t=40 mins (exercise session completion)

Secondary outcome [15]

Mean glucose on continuous glucose monitor.

Timepoint [15]

Mean glucose will be monitored in the acute post-exercise period from T=0 - T=24 hrs post-exercise.

Secondary outcome [16]

Glucose management indicator on continuous glucose monitor.

Timepoint [16]

Glucose management indicator will be monitored in the acute post-exercise period from T=0 - T= 24 hrs post-exercise

Secondary outcome [17]

Glycaemic variability on continuous glucose monitor.

Timepoint [17]

Glycaemic variability will be monitored in the acute post-exercise period from T=0 - T=24 hrs post-exercise.

Secondary outcome [18]

Percentage time above range (>13.9 mmol/L) on continuous glucose monitor.

Timepoint [18]

Percentage time above range (>13.9 mmol/L) will be monitored in the acute post-exercise period from T=0 - T=24 hrs post-exercise.

Secondary outcome [19]

Percentage time between range (10.1-13.9 mmol/L) on continuous glucose monitor.

Timepoint [19]

Percentage time between range (10.1-13.9 mmol/L) will be monitored in the acute post-exercise period from T=0 - T=24 hrs post-exercise

Secondary outcome [20]

Percentage time between range (3.0-3.8 mmol/L) on continuous glucose monitor.

Timepoint [20]

Percentage time between range ( 3.0-3.8 mmol/L) will be monitored in the acute post-exercise period from T=0 - T=24 hrs post-exercise

Secondary outcome [21]

Percentage time below range (<3.0 mmol/L) on continuous glucose monitor.

Timepoint [21]

Percentage time below range will be monitored in the acute post-exercise period from T=0 - T=24 hrs post-exercise.

Secondary outcome [22]

Glycaemic risk index

Timepoint [22]

Glycaemic risk index will be monitored in the acute post-exercise period from T=0 - T=24 hrs post-exercise.

Secondary outcome [23]

Percentage time ketone levels above 0.6 mmol/L

Timepoint [23]

Percentage time ketone levels above (0.6 mmol/L) will be monitored in the acute post-exercise period from T= 0 - T=24 hrs post-exercise.

Secondary outcome [24]

Percentage time ketone levels above 1.5 mmol/L

Timepoint [24]

Percentage time ketone levels above (1.5 mmol/L) will be monitored in the acute post-exercise period from T= 0 - T=24 hrs post-exercise.

Secondary outcome [25]

Percentage time ketone levels above 3.0 mmol/L

Timepoint [25]

Percentage time ketone levels above (3.0 mmol/L) will be monitored in the acute post-exercise period from T= 0 - T=24 hrs post-exercise.

Eligibility

Key inclusion criteria

Age equal to or greater than 18 years; type 1 diabetes of more than 1 year duration; stable on insulin therapy; HbA1c <10.0%; access to a mobile phone compatible with the ketone monitoring system; willing to adhere to all requirements of the protocol including wearing and responding to information provided by the continuous ketone sensor for the duration of the study.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Pregnancy or planned pregnancy; eGFR<30 ml/minute/1.73m2; a history of diabetic ketoacidosis in the last 3 months; diabetic gastroparesis; tape allergy; unable to exercise; use of low carbohydrate diet; heavy alcohol use; major medical or psychiatric illness that in the opinion of the investigator would interfere with protocol adherence or impact participant safety.

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 will be concealed by bottles that are independently labelled at a central administration site

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

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 administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Crossover

Other design features

Phase

Phase 2

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

2/09/2024

Actual

Date of last participant enrolment

Anticipated

3/03/2025

Actual

Date of last data collection

Anticipated

2/09/2025

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

St Vincent's Private Hospital - Fitzroy

Recruitment hospital [2]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [3]

Royal Melbourne Hospital - Royal Park campus - Parkville

Recruitment postcode(s) [1]

3065 - Fitzroy

Recruitment postcode(s) [2]

3084 - Heidelberg

Recruitment postcode(s) [3]

3052 - Parkville

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

The Australian Centre for Accelerating Diabetes Innovations

Address [1]

Country [1]

Australia

Primary sponsor type

Hospital

Name

St Vincent's Hospital Melbourne

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

St Vincent’s Hospital Human Research Ethics Committee

Ethics committee address [1]

https://svhs.org.au/home/research-education/research-office

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

20/05/2024

Approval date [1]

11/06/2024

Ethics approval number [1]

Summary

Brief summary

When people with Diabetes exercise it can make their blood sugar drop too low, for this doctors recommend ways to adjust insulin before exercising. SGLT Inhibitors can increase the risk of Diabetic Ketoacidosis. The Abbott Sensor-Based Ketone Monitoring system will be used to assess the effect ketone responses during exercise in people with type 1 diabetes. We believe that ketones will risk in individuals that undertake high intensity interval exercise.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof David O'Neal

Address

University of Melbourne Dept of Medicine, St Vincent's Hospital Melbourne, 41 Victoria Parade Fitzroy, VIC, 3065

Country

Australia

Phone

+61 425731665

Fax

[email protected]

Contact person for public queries

Name

Audrey Kong

Address

University of Melbourne Dept of Medicine, St Vincent's Hospital Melbourne, 41 Victoria Parade Fitzroy, VIC, 3065

Country

Australia

Phone

+61 433593020

Fax

[email protected]

Contact person for scientific queries

Name

David O'Neal

Address

University of Melbourne Dept of Medicine, St Vincent's Hospital Melbourne, 41 Victoria Parade Fitzroy, VIC, 3065

Country

Australia

Phone

+61 425731665

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.

Trial Review

Documents added manually

Documents added automatically