Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001304527
Ethics application status
Approved
Date submitted
4/10/2024
Date registered
28/10/2024
Date last updated
28/10/2024
Date data sharing statement initially provided
28/10/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Personalised antioxidant treatment for type 2 diabetes
Scientific title
Investigating the efficacy of personalised antioxidant supplementation for the treatment of type 2 diabetes in participants aged 35 to 75 years
Secondary ID [1] 312419 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 335375 0
Condition category
Condition code
Metabolic and Endocrine 331951 331951 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will assess the effect of targeted and untargeted antioxidant treatments on glycaemic control in people with type 2 diabetes. Eighty individuals with type 2 diabetes will be enrolled in phase 1 of the study (antioxidant screening) to identify individuals with low vitamin C levels, low glutathione levels, and optimal levels of these two antioxidants. Once all 80 participants have been enrolled, blood collection for plasma vitamin C and erythrocyte glutathione measurement will be performed in all participants. Participants will then be allocated into three groups (n = 15 per group) based on their vitamin C and glutathione levels: 1) low vitamin C group (the 15 participants with the lowest vitamin C levels); 2) low glutathione group (the 15 participants with the lowest glutathione levels); 3) control antioxidant group (15 participants with vitamin C and glutathione levels in the top 50%). Participants who are identified as having low levels of both vitamin C and glutathione will be excluded and replaced by the participant with the next lowest antioxidant levels. If the number of participants with vitamin C and glutathione levels in the top 50% does not equal 15, the 15 participants with the highest composite score for these two antioxidants will be selected. Participants who do not fall into one of these three groups will be excluded from the remainder of the study.

In phase 2 of the study (antioxidant treatment), participants in each of the three groups will consume tablets containing vitamin C (1000 mg/day) (arm 1) and N-acetylcysteine (1200 mg/day) (arm 2) for 90 days in a double-blind, randomised, crossover design with a 30-day washout period. N-acetylcysteine is converted to cysteine in the liver, which is used to produce glutathione. The order in which participants complete arms 1 and 2 will be randomised. Adherence to the intervention will be assessed using participant diaries and by oversupplying tablets and counting the tablets remaining at the end of the intervention. Glycaemic control (continuous glucose monitor; CGM and HbA1c), exercise capacity, vascular function, arterial stiffness, blood pressure, body composition (dual-energy x-ray absorptiometry), plasma vitamin C levels, erythrocyte glutathione levels, and oxidative stress (urine F2-isoprostanes) will be assessed before and after vitamin C and N-acetylcysteine supplementation over a 3-day testing period. On day 1, participants will provide a fasted blood and urine sample and have their blood pressure and body composition assessed. Participants will be fitted with a CGM and an activity monitor and will be provided with a standardised diet to consume over the 48-hour period of CGM recording. The standardised diet will include three main meals and two snacks per day. Continuous glucose data collected during the 24 hours commencing at midnight on day 2 will be used for subsequent analysis. On day 3, endothelium-dependent and -independent vascular function will be measured using brachial flow-mediated dilation and sub-lingual glyceryl trinitrate techniques. Arterial stiffness will be assessed non-invasively as carotid-femoral pulse wave velocity via applanation tonometry. Exercise capacity will be assessed determined during a graded exercise test on a stationary bike using open-circuit spirometry with concurrent electrocardiography and blood pressure measurements.
Intervention code [1] 329698 0
Treatment: Other
Comparator / control treatment
Vitamin C treatment (arm 1) will be the comparator/control treatment. The low vitamin C and low glutathione groups will be compared to the control antioxidant group.
Control group
Active

Outcomes
Primary outcome [1] 339561 0
Postprandial glucose incremental area under the curve
Timepoint [1] 339561 0
Before and after vitamin C and N-acetylcysteine supplementation.
Secondary outcome [1] 440432 0
Glycated hemoglobin (HbA1c)
Timepoint [1] 440432 0
Before and after vitamin C and N-acetylcysteine supplementation
Secondary outcome [2] 440433 0
Vascular function
Timepoint [2] 440433 0
Before and after vitamin C and N-acetylcysteine supplementation
Secondary outcome [3] 440434 0
Arterial stiffness
Timepoint [3] 440434 0
Before and after vitamin C and N-acetylcysteine supplementation
Secondary outcome [4] 440435 0
Exercise capacity
Timepoint [4] 440435 0
Before and after vitamin C and N-acetylcysteine supplementation
Secondary outcome [5] 440436 0
Body composition
Timepoint [5] 440436 0
Before and after vitamin C and N-acetylcysteine supplementation
Secondary outcome [6] 440437 0
Plasma vitamin C
Timepoint [6] 440437 0
Before and after vitamin C and N-acetylcysteine supplementation
Secondary outcome [7] 440438 0
Erythrocyte glutathione
Timepoint [7] 440438 0
Before and after vitamin C and N-acetylcysteine supplementation
Secondary outcome [8] 440439 0
Oxidative stress
Timepoint [8] 440439 0
Before and after vitamin C and N-acetylcysteine supplementation

Eligibility
Key inclusion criteria
Aged between 35 and 75 years
Diagnosis of type 2 diabetes
>3 months since type 2 diabetes diagnosis
Management with diet or anti-hyperglycaemic medications excluding insulin
No changes to medication in the previous 3 months
stable HbA1c greater than or equal to 6.5%
Minimum age
35 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Taking insulin
BMI > 35 kg/m2
Systolic BP (SBP) > 160 mm Hg
Diastolic BP (DBP) > 90 mm Hg
Smoker
Heart murmur
Bleeding disorder or haemochromatosis
Renal or liver diseases
Taking antioxidant vitamin supplements
Pregnant or planning a pregnancy

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)
Participants will be given the vitamin C and N-acetylcysteine tablets in numbered containers
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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary outcome of this study will be postprandial glucose incremental area under the curve (iAUC) above basal glucose, assessed as the cumulative total (10.5 hours) of the 3.5-hour postprandial periods after each main meal consumed. Based on published data, the standard deviation for postprandial glucose iAUC is 240 mmol/L/10.5 h. The sample size for this study was determined based on previous research, which showed that 4 weeks of vitamin C supplementation reduced postprandial glucose iAUC by 27%. Using an F-test power analysis to detect differences among the means of multiple groups, the required sample size was calculated using G*Power v3.1 based on an assumed effect size of 0.25 (medium effect size), a significance level of 0.05, and a desired power of 80%. Considering 3 groups with equal sample sizes, the total sample size required was calculated to be 36 participants (12 per group). To account for potential dropout, we increased the sample size by 25% resulting in a sample size of 45 participants (15 per group). 80 participants will be recruited to the study to enable screening for antioxidant levels,

A two-way repeated measures ANOVA [group (control, low vitamin C and low glutathione) × time (pre- and post-supplementation)] will be performed for each antioxidant scheme (i.e., 90 days vitamin C or NAC supplementation) to compare the effect of the antioxidant intervention on glycaemic control, exercise capacity, and vascular function in the three experimental groups.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2025
Actual
Date of last participant enrolment
Anticipated
31/07/2025
Actual
Date of last data collection
Anticipated
1/02/2027
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 316832 0
Charities/Societies/Foundations
Name [1] 316832 0
European Society for Clinical Nutrition and Metabolism
Country [1] 316832 0
France
Primary sponsor type
Charities/Societies/Foundations
Name
European Society for Clinical Nutrition and Metabolism
Address
Country
France
Secondary sponsor category [1] 319867 0
None
Name [1] 319867 0
Address [1] 319867 0
Country [1] 319867 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315600 0
ACU Human Research Ethics Committee
Ethics committee address [1] 315600 0
Ethics committee country [1] 315600 0
Australia
Date submitted for ethics approval [1] 315600 0
09/04/2024
Approval date [1] 315600 0
09/08/2024
Ethics approval number [1] 315600 0
2024-3636HC

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

Contacts
Principal investigator
Name 135206 0
Dr Sophie Broome
Address 135206 0
Australian Catholic University Building 420, Level 5 215 Spring Street, Melbourne, VIC 3000
Country 135206 0
Australia
Phone 135206 0
+61 421717852
Fax 135206 0
Email 135206 0
[email protected]
Contact person for public queries
Name 135207 0
Sophie Broome
Address 135207 0
Australian Catholic University Building 420, Level 5 215 Spring Street, Melbourne, VIC 3000
Country 135207 0
Australia
Phone 135207 0
+61 421717852
Fax 135207 0
Email 135207 0
[email protected]
Contact person for scientific queries
Name 135208 0
Sophie Broome
Address 135208 0
Australian Catholic University Building 420, Level 5 215 Spring Street, Melbourne, VIC 3000
Country 135208 0
Australia
Phone 135208 0
+61 421717852
Fax 135208 0
Email 135208 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.