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Trial registered on ANZCTR


Registration number
ACTRN12618001120268
Ethics application status
Approved
Date submitted
29/06/2018
Date registered
6/07/2018
Date last updated
29/01/2019
Date data sharing statement initially provided
29/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Zinc in Preventing the Progression of Pre-Diabetes
Scientific title
Zinc in Preventing the Progression of Pre-Diabetes
Secondary ID [1] 295003 0
None
Universal Trial Number (UTN)
Trial acronym
ZIPPeD Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pre-Diabetes 308586 0
Condition category
Condition code
Metabolic and Endocrine 307539 307539 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Intervention is a zinc gluconate 30mg capsule supplement to be taken once daily for one year. Outcome data for this trial will be ascertained through changes in HbA1c levels at baseline, one month, six months and twelve months, in the two arms of the study.
Participants will be provided a reply paid padded envelope to return the unused capsules, which will be counted for compliance and acceptability of the supplement. All participants will receive standard care with the intervention. Standard care is a NSW health initiative called the "Get Healthy Information and Coaching Service", to improve the lifestyle (smoking, exercise, alcohol use, weight losss) of persons with pre-diabetes.
The "Get Healthy Information and Coaching Service", will provide 13 health motivational phone calls to all participants over a 6 month period.
Intervention code [1] 301685 0
Prevention
Intervention code [2] 301686 0
Treatment: Drugs
Comparator / control treatment
The Placebo is a cellulose capsule and will be a white opaque hard capsule the same size and shape as the active. The control group also receive standard care ("Get Healthy Information and Coaching Service") for 6 months.
Control group
Placebo

Outcomes
Primary outcome [1] 306518 0
Change in HbA1c.
Timepoint [1] 306518 0
1 year post intervention commencement.
Primary outcome [2] 306545 0
Change in insulin sensitivity (as per HOMA model)
Timepoint [2] 306545 0
1 year post-intervention commencement
Secondary outcome [1] 348756 0
progression to diabetes (as per HbA1c)
Timepoint [1] 348756 0
1 year post intervention commencement.
Secondary outcome [2] 348757 0
change in CVD risk factors (as measured by Cholesterol)
Timepoint [2] 348757 0
1 year post intervention commencement.
Secondary outcome [3] 348758 0
change in CVD risk factors (as measured by BMI and waist circumference)
Timepoint [3] 348758 0
1 year post intervention commencement.
Secondary outcome [4] 348759 0
acceptability of supplements (as measured by pill counts)
Timepoint [4] 348759 0
1 year post intervention commencement.

Eligibility
Key inclusion criteria
Prediabetes, defined by a HbA1c of 5.7-6.4 and BMI greater than 28
Minimum age
40 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
One or more of the following:
Taking any other vitamin or mineral supplementation containing zinc;
Currently using weight loss medication;
Pregnancy or lactation for women of child-bearing age;
Impaired hepatic or renal function;
Taking pharmacology agents that may interfere with the intervention (for example, metformin, and complementary medicines).
Any condition that, in the opinion of the investigator, does not justify the patient’s inclusion in the study (current cancer under treatment, terminal cancer, terminal illness).
Persons who are unable to read and understand the information statement and consent form are ineligible. Informed consent must be obtained to be eligible for the study.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Medications labelled A and B by an independent party, and randomisation assigned as A and B by the independent study statistician
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple permuted block randomisation using a randomisation table created by independent study statistician
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
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Analyses will be undertaken in accord with the CONSORT guidelines (http://www.consort-statement.org/) and by an independent statistician at the (CReDITSS) unit.
Effectiveness of zinc (Q1):
Primary analysis: HOMA-derived insulin sensitivity at baseline, 1,3, 6 and 12 months will be plotted to assess response trajectories. We will fit a linear mixed model (LMM) with insulin resistance as the dependent variable, and fixed effects for time (categorical predictor), group, and time by group interaction terms. This will allow us to identify the time points at which maximal group differences are observed. A random intercept will be included to account for repeated measures on participants and the model will be adjusted for baseline age, gender, physical activity, and diet quality. The LMM uses all available values for each participant and provides robust effect estimates assuming data are missing at random. All statistical analyses will observe the intention to treat principle.
Secondary analyses: A similar LMM approach will be used to jointly analyse the baseline, 1, 3, 6 and 12 month for insulin resistance, beta-cell function, FPG, HbA1c, lipids, and other secondary outcomes across the zinc and control groups.
Effectiveness of Get Healthy T2DM Prevention Program (Q2):
Primary analysis: HbA1c values at baseline, 1, 3, 6 and 12 months will also be plotted for the placebo group alone, to allow us to estimate the effect of Get Healthy, without zinc supplementation. We will fit a LMM with fixed effects for time as our categorical predictor and HbA1c as the dependent variable. This will allow us to identify pre vs post differences due to lifestyle changes. A random intercept will be included to account for repeated measures on participants and the model will be adjusted for baseline age, gender, physical activity, and diet quality.
Secondary analyses: A similar LMM approach will be used to jointly analyse the baseline, 1, 3, 6 and 12 month data for BMI, waist/hip ratio, and blood pressure. In addition, completion rates for the Get Healthy program for those referred as part of the study will be benchmarked to current rates for those referred through other sources.
Cost effectiveness of zinc and Get Healthy T2DM Prevention program (Q3):
Direct analyses: The cost effectiveness of zinc supplementation will be assessed in a trial-based analysis. The analysis will adopt a modified societal perspective to account for health care system costs as well as patient costs, which would be incurred if the zinc supplement was an out-of-pocket expense. The incremental cost effectiveness ratio (ICER) will be calculated as the difference in average cost between the zinc supplementation group and placebo group, divided by the difference in average FPG level. Uncertainty intervals for the incremental costs and ICER will be calculated using a non-parametric bootstrap procedure to reflect sampling uncertainty. Sensitivity analysis will examine imputation uncertainty, comparing the reference case results to the analysis of participants with complete data. Additional sensitivity analysis will involve variation in the market price of zinc capsules.
Modelled analyses:
• The results from the trial-based analysis will be extrapolated in a cost-consequence analysis comparing the health care resource use profiles for two cohorts over a five year period: those people with delayed progression to diabetes as a results of zinc supplementation in conjunction with effective lifestyle modification and those people who follow the natural history of diabetes progression.
• A second modelled analysis will extrapolate the results from the trial-based analysis and transform the intermediate, primary trial outcome into a final, patient relevant outcome: quality adjusted life years saved. The cost utility analysis will model costs, expected cost savings and patient outcomes over the lifetime of a hypothetical cohort of prediabetic patients.
Similar direct and modelled analyses will be performed for the evaluation of Get Healthy T2DM Prevention Program, looking at pre- and post- glycaemic markers.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 23146 0
2305 - New Lambton Heights
Recruitment postcode(s) [2] 23147 0
2308 - Newcastle University

Funding & Sponsors
Funding source category [1] 299588 0
Government body
Name [1] 299588 0
NSW Ministry of Health
Address [1] 299588 0
Locked bag 961, North Sydney NSW 2059
Country [1] 299588 0
Australia
Primary sponsor type
Individual
Name
Professsor John Attia
Address
Level 3 The Pod
Hunter Medical Research Institute
1 Kookaburra Ct
New Lambton Heights NSW 2305
Country
Australia
Secondary sponsor category [1] 298903 0
University
Name [1] 298903 0
The University of Newcastle
Address [1] 298903 0
University Drive Callaghan, NSW 2308
Country [1] 298903 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300489 0
Hunter New England Human Research Ethics
Ethics committee address [1] 300489 0
Hunter New England Local Health District
The Lodge, Rankin Park Campus
Locked Bag 1, New Lambton, NSW, 2305
Ethics committee country [1] 300489 0
Date submitted for ethics approval [1] 300489 0
29/06/2018
Approval date [1] 300489 0
27/07/2018
Ethics approval number [1] 300489 0
HNEHREC: 18/07/18/3.03

Summary
Brief summary
The study is a randomised, placebo-controlled, double-blind trial. Participants aged 40-70 with pre-diabetes (as per HbA1c) will be invited to participate through GP Practices involved in the diabetes alliance. Participants will be randomly allocated on a ratio1:1, to receive zinc or control treatment options, and followed up at one month, three months, six months and twelve months. Both treatment arms will have Get Healthy Information and Coaching Service, type 2 diabetes Prevention Program involved in their care for the first six months of the trial.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83822 0
Prof John Attia
Address 83822 0
Level 3, The Pod
HMRI Building
1 Kookaburra Ct
New Lambton Heights 2305 NSW
Country 83822 0
Australia
Phone 83822 0
+61240420500
Fax 83822 0
Email 83822 0
john.attia@newcastle.edu.au
Contact person for public queries
Name 83823 0
Prof John Attia
Address 83823 0
Level 3, The Pod
HMRI Building
1 Kookaburra Ct
New Lambton Heights 2305 NSW
Country 83823 0
Australia
Phone 83823 0
+61240420500
Fax 83823 0
Email 83823 0
john.attia@newcastle.edu.au
Contact person for scientific queries
Name 83824 0
Prof John Attia
Address 83824 0
Level 3, The Pod
HMRI Building
1 Kookaburra Ct
New Lambton Heights 2305 NSW
Country 83824 0
Australia
Phone 83824 0
+61240420500
Fax 83824 0
Email 83824 0
john.attia@newcastle.edu.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?
Ethical approval
How or where can supporting documents be obtained?
Type [1] 211 0
Ethical approval
Citation [1] 211 0
Link [1] 211 0
Email [1] 211 0
Other [1] 211 0
Summary results
No Results