Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000020684
Ethics application status
Approved
Date submitted
2/11/2022
Date registered
10/01/2023
Date last updated
2/08/2023
Date data sharing statement initially provided
10/01/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Can personalised antioxidant screening and prescription improve cardiovascular and metabolic health in individuals with pre-diabetes and type 2 diabetes: PRESCRIBE.
Scientific title
Can personalised antioxidant screening and prescription improve cardiovascular and metabolic health in individuals with pre-diabetes and type 2 diabetes: PRESCRIBE.
Secondary ID [1] 308310 0
GNT105590
Universal Trial Number (UTN)
U1111-1284-4811
Trial acronym
PRESCRIBE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 328095 0
Vitamin C deficiency 328636 0
Condition category
Condition code
Metabolic and Endocrine 325150 325150 0 0
Diabetes
Diet and Nutrition 325642 325642 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Clinical Trial Registry
This study is a single-site, parallel, randomized controlled trial comparing the effect of 3 months of personalised antioxidant treatment to generic antioxidant treatment and placebo.
Clinical chemistries and anthropometrics: Fasting clinical chemistries (glucose, insulin, lipid profile, HbA1c, lactate) and body composition (height, weight, hip and waist circumferences and lean/fat mass by dual-energy X-ray absorptiometry) will be measured. Medical, lifestyle and dietary questionnaires will be used to assess overall health, physical activity and dietary habits.

Vascular function and metabolic responses to exercise (maximal and functional capacity) and mixed nutrient meal ingestion will be performed before and after the 3-month intervention (personalised antioxidant treatment, generic antioxidant treatment, and placebo).

Maximal and functional exercise capacity: Maximal exercise capacity will be assessed using a symptom limited graded exercise test on a treadmill and standard cardiopulmonary stress equipment. Functional exercise capacity will be assessed with a 6-minute walk test and 2-minute step test.

Mixed nutrient meal test: Participants will be provided a mixed nutrient meal to consume within 5 minutes. The mixed meal constitutes 1256 kJ of total energy (approximately 21.6 g protein, 4.9 g fat, 40 g carbohydrate).

Vascular measures: Resting and post-exercise echocardiographic assessment will be performed using a commercial ultrasound machine. Microvascular blood flow in skeletal muscle will be measured via contrast enhanced ultrasound imaging of the thigh muscle. Femoral artery blood velocity, diameter and flow will be assessed using 2D and Doppler imaging.

Quality of life will be assessed via EuroQol five-dimensional questionnaire (EQ5D) and the 36-Item Short Form Health Survey (SF-36).

3-MONTH INTERVENTION
Vitamin C levels will be assessed during the screening phase. Participants will be classified as having either “low vitamin C” (less than 28 µmol/L) or “normal vitamin C” (greater than or equal to 28 µmol/L) using standard clinical cut-offs for vitamin C levels. Both a low vitamin C group and a normal vitamin C group will be split and randomised to undergo either 3 months of personalised antioxidant treatment, generic antioxidant treatment, or placebo. Groups will be matched for age, BMI, sex, glucose management (HbA1c levels) and exercise capacity (VO2peak). The “low vitamin C” groups that undergo personalised, generic, and placebo treatment, will be counterbalanced to ensure that individuals with a vitamin C deficiency of less than 11 µmol/L will be similar across groups.

Individuals with low vitamin C level will be randomised to:
• Personalised antioxidant treatment (n = 26): Oral vitamin C (2 x 500 mg/day) for 12 weeks, as previously done in healthy adults.
• Placebo treatment (n = 26): Oral placebo capsules containing an inert powder (Avicel) (2 x 500 mg/day).

Individuals with normal vitamin C level will be randomised to:
• Generic antioxidant treatment (n = 26): Oral vitamin C (2 x 500 mg/day) for 12 weeks, as previously done in healthy adults.
• Placebo treatment (n = 26): Oral placebo capsules containing an inert powder (Avicel) (2 x 500 mg/day).

Capsule counting will be conducted to measure compliance of the antioxidant and placebo intervention.

Note: Vitamin C supplementation in individuals with normal vitamin C levels is considered generic treatment as it is not targeting a specific deficiency, and therefore hypothesised to be less effective at improving health outcomes.
Intervention code [1] 324762 0
Treatment: Drugs
Comparator / control treatment
Individuals with low vitamin C levels (n = 26) and normal vitamin C levels (n = 26) randomised to the control group will be treated with oral placebo capsules containing an inert powder (Avicel) (2 x 500 mg/day), for 3 months.
Control group
Placebo

Outcomes
Primary outcome [1] 332999 0
Change in exercise capacity (peak volume of oxygen utilisation) assessed by metabolic cart and oxygen analyser during the graded exercise test..
Timepoint [1] 332999 0
Exercise capacity (peak volume of oxygen utilisation) measured during the graded exercise test both before and after the 3-month intervention.
Secondary outcome [1] 415500 0
Change in functional exercise capacity (distance walked) assessed by the 6-minute walk test.
Timepoint [1] 415500 0
Functional exercise capacity (distance walked) measured after the 6-minute walk test both before and after the 3-month intervention.
Secondary outcome [2] 415501 0
Change in functional exercise capacity (number of steps taken) assessed by the 2-minute step test.
Timepoint [2] 415501 0
Functional exercise capacity (number of steps taken) measured during the 2-minute step test both before and after the 3-month intervention.
Secondary outcome [3] 415502 0
Change in peak post-exercise microvascular blood flow (Arbitrary units) measured by contrast enhanced ultrasound after the 3-month intervention.
Timepoint [3] 415502 0
Peak post-exercise microvascular blood flow measured before and after the 3-month intervention.
Secondary outcome [4] 417251 0
Change in peak meal-induced microvascular blood flow (Arbitrary units) measured by contrast enhanced ultrasound after the 3-month intervention.
Timepoint [4] 417251 0
Peak meal-induced microvascular blood flow measured before and after the 3-month intervention.
Secondary outcome [5] 417252 0
Resting cardiac output measured by echocardiography.
Timepoint [5] 417252 0
Resting cardiac output measured before and after the 3 month intervention.
Secondary outcome [6] 417253 0
Resting left ventricular ejection fraction measured by echocardiography.
Timepoint [6] 417253 0
Resting left ventricular ejection fraction measured before and after the 3 month intervention.
Secondary outcome [7] 417254 0
Post-exercise left ventricular ejection fraction measured by echocardiography.
Timepoint [7] 417254 0
Post-exercise left ventricular ejection fraction measured before and after the 3 month intervention.
Secondary outcome [8] 417255 0
Post-exercise cardiac output measured by echocardiography.
Timepoint [8] 417255 0
Post-exercise cardiac output measured before and after the 3 month intervention.
Secondary outcome [9] 417256 0
Quality of life scores measured by the EQ-5D questionnaire
Timepoint [9] 417256 0
Quality of life scores (EQ-5D) measured before and after the 3 month intervention.
Secondary outcome [10] 417257 0
Quality of life scores measured by the SF-36 questionnaire.
Timepoint [10] 417257 0
Quality of life scores (SF-36) measured before and after the 3 month intervention.
Secondary outcome [11] 417258 0
Femoral artery blood flow measured via ultrasound.
Timepoint [11] 417258 0
Femoral artery blood flow measured before and after the 3 month intervention.
Secondary outcome [12] 417259 0
Femoral artery diameter measured via ultrasound.
Timepoint [12] 417259 0
Femoral artery diameter measured before and after the 3 month intervention.
Secondary outcome [13] 417260 0
Femoral artery blood velocity measured via ultrasound
Timepoint [13] 417260 0
Femoral artery blood velocity measured before and after the 3 month intervention.

Eligibility
Key inclusion criteria
1. Aged 40–80 years.
2. Clinical diagnosis of pre-diabetes (HbA1C greater than or equal to 5.7%) or type 2 diabetes (T2D) (HbA1C greater than or equal to 6.5%)
- Controlled diabetes through diet or medication (excluding insulin) for 8 weeks or longer.
3. Have given signed informed consent to participate in the study.
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:
1. Patients using insulin to control blood sugar levels.
2. Pulmonary hypertension.
3. Atrial fibrillation.
4. Cardiovascular disease including coronary artery disease or heart valve disease.
5. Poor ejection fraction (less than 50%) or elevated left ventricle filling pressure (E/e’ greater than 15).
6. Critical limb ischemia including peripheral artery disease or previous revascularisation or other surgical treatment for peripheral artery disease.
7. History of malignancy within past 5 years (except for non-melanoma skin cancers).
8. Identification of any medical condition requiring immediate therapeutic intervention.
9. Uncontrolled hypertension (resting brachial blood pressure greater than or equal to 160/100 mmHg).
10. Other musculoskeletal conditions and non-cardiovascular barriers to exercise/physical activity.
11. Current or previous smoker with past 12 months.
12. Participation or intention to participate in a structured and/or supervised physical activity program during the study period.
13. History of severe liver disease.
14. History of kidney disease or impaired kidney function.
15. Elective major surgery during the course of the study.
16. Taking medications or supplements that may affect the study outcomes (e.g., vitamin C, E or D).
17. Pregnancy/lactation.

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be first classified and stratified into two groups of either low vitamin C levels or normal vitamin C levels, and subsequently randomised via block randomisation into the two intervention arms (vitamin c treatment or placebo)
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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be checked for normality and analysed using Predictive Analytics Software (PASW v20, SPSS Inc.). Comparison of means between groups will be compared using analysis of variance (ANOVA) and multivariable linear regression where appropriate. Comparison of multiple means will be analysed using a three-way repeated measures ANOVA with time (before and after exercise tests, before and after mixed meal ingestion, and before and after the intervention) as the within-subjects factor, and intervention (vitamin C or placebo) and vitamin C level (low and normal) as the between-subjects factors. Significant interaction and main effects will be explored post-hoc with corrections for multiple comparisons. Planned multiple comparisons will also be conducted between the variables of interest (e.g., delta change in variables between groups). Statistical analysis will be conducted at the 95% level of significance (p = 0.05).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
14/08/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
104
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 312557 0
Charities/Societies/Foundations
Name [1] 312557 0
National Heart Foundation of Australia
Country [1] 312557 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
221 Burwood Hwy, Burwood VIC 3125
Country
Australia
Secondary sponsor category [1] 314162 0
None
Name [1] 314162 0
Address [1] 314162 0
Country [1] 314162 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311884 0
Deakin University Human Research Ethics Committee
Ethics committee address [1] 311884 0
Ethics committee country [1] 311884 0
Australia
Date submitted for ethics approval [1] 311884 0
Approval date [1] 311884 0
23/08/2022
Ethics approval number [1] 311884 0

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

Contacts
Principal investigator
Name 122718 0
Dr Lewan Parker
Address 122718 0
Deakin University, 221 Burwood Highway, Burwood, VIC, 3125
Country 122718 0
Australia
Phone 122718 0
+61 3 9246 8740
Fax 122718 0
Email 122718 0
[email protected]
Contact person for public queries
Name 122719 0
Lewan Parker
Address 122719 0
Deakin University, 221 Burwood Highway, Burwood, VIC, 3125
Country 122719 0
Australia
Phone 122719 0
+61 3 9246 8740
Fax 122719 0
Email 122719 0
[email protected]
Contact person for scientific queries
Name 122720 0
Lewan Parker
Address 122720 0
Deakin University, 221 Burwood Highway, Burwood, VIC, 3125
Country 122720 0
Australia
Phone 122720 0
+61 3 9246 8740
Fax 122720 0
Email 122720 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.