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Trial registered on ANZCTR


Registration number
ACTRN12618000858291
Ethics application status
Approved
Date submitted
15/05/2018
Date registered
22/05/2018
Date last updated
9/03/2020
Date data sharing statement initially provided
9/03/2020
Date results information initially provided
9/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Acute effect of the oral contraceptive pill on glucose regulation
Scientific title
Acute effect of the oral contraceptive pill on glucose homeostasis in healthy women
Secondary ID [1] 294876 0
None
Universal Trial Number (UTN)
U1111-1214-0302
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 307827 0
Obesity 307828 0
Condition category
Condition code
Metabolic and Endocrine 306875 306875 0 0
Diabetes
Diet and Nutrition 306889 306889 0 0
Obesity

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
We will conduct a study of 18 New Zealand healthy women (18 – 40 years old, normal BMI). These women will be regular users of the monophasic combined oral contraceptive pill. We will measure metabolic response to an oral glucose challenge of 60g of glucose dissolved in 490ml water + 10ml of lemon juice administered after a 12 hour fast (water allowed) during both phases of contraceptive pill use (once during the 21 days of hormone-containing pills, and once during the 7 days of non-hormone (sugar) pills).




Intervention code [1] 301225 0
Not applicable
Comparator / control treatment
As we will conduct the oral glucose challenge during during both phases of contraceptive pill use (once during the 21 days of hormone-containing pills, and once during the 7 days of non-hormone (sugar) pills) the women are acting as their own comparator..
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305866 0
Plasma profile of metabolic biomarkers (e.g, glucose, insulin, C-peptide) as assessed by Roche/Hitachi Cobas auto-analyser and multiplex assays.
Timepoint [1] 305866 0
Baseline (Fasted) - T-15 minutes
Post-prandial - T15 minutes, T30 minutes, T60 minutes, T90 minutes, T120 minutes, T180 minutes, T240 minutes

There is no one primary timepoint as we will look at the area under the curve (AUC).
Primary outcome [2] 305867 0
Metabolic rate (energy expenditure) measured by indirect calorimetery using an open-circuit ventilated hood system (Quark, Cosmed srl, Rome, Italy).

Timepoint [2] 305867 0
Baseline (Fasted) - T-45 to T0 minutes
Post-prandial - continuous measurement from T15 minutes to T245 minutes

There is no one primary timepoint as we will look at the area under the curve (AUC).
Secondary outcome [1] 346844 0
Blood pressure as measured byWelch Allyn ProBP 2400 electronic blood pressure device
Timepoint [1] 346844 0
Baseline (Fasted) - T-15 minutes
Post-prandial - T60 minutes, T120 minutes, T180 minutes, T240 minutes, T280 minutes
Secondary outcome [2] 346848 0
Body temperature as measured by tympanic thermometer (Braun Thermoscan Pro 6000)
Timepoint [2] 346848 0
Baseline (Fasted) - T-45 minutes
Post-prandial- T245 minutes and T280 minutes
Secondary outcome [3] 346849 0
Appetite (hunger, fullness, ability to eat, comfort and nausea), as measured by Visual Analogue Scales
Timepoint [3] 346849 0
Baseline (fasted) - T-30 minutes, T-15 minutes, T0 minutes
Post-prandial - T15 minutes, T30 minutes, T60 minutes, T90 minutes, T120 minutes, T180 minutes, T210 minutes, T240 minutes, T280 minutes
Secondary outcome [4] 346850 0
Energy intake as measured by ad lib consumption of a standardised lunch meal. All food items will be double weighed before and after the lunch meal and dietary analysis software (FoodWorks) will be used to calculate the amount of energy consumed.
Timepoint [4] 346850 0
T250 minutes
Secondary outcome [5] 346957 0
Plasma profile of biomarkers of cardiovascular risk (e.g. total cholesterol, triglycerides) as assessed by Roche/Hitachi Cobas auto-analyser and multiplex assays.
Timepoint [5] 346957 0
Baseline (Fasted) - T-15 minutes
Secondary outcome [6] 346958 0
Plasma profile of inflammatory biomarkers (e.g. CRP, TNF-a) as assessed by Roche/Hitachi Cobas auto-analyser and multiplex assays.
Timepoint [6] 346958 0
Baseline (Fasted) - T-15 minutes
Secondary outcome [7] 346959 0
Plasma profile of gut peptides/markers of appetite control (e.g. leptin, GLP-1) as assessed by Roche/Hitachi Cobas auto-analyser and multiplex assays.
Timepoint [7] 346959 0
Baseline (Fasted) - T-15 minutes
Post-prandial - T15 minutes, T30 minutes, T60 minutes, T90 minutes, T120 minutes, T180 minutes, T240 minutes
Secondary outcome [8] 346960 0
Plasma profile of hormones (e.g. cortisol, estrogens, thyroxine) as assessed by Roche/Hitachi Cobas auto-analyser and multiplex assays.
Timepoint [8] 346960 0
Baseline (Fasted) - T-15 minutes
Secondary outcome [9] 346961 0
Heart rate as assessed by chest belt (Garmin).
Timepoint [9] 346961 0
Baseline (Fasted) - T-45 minutes to T0 minutes
Post-prandial - continuous measurement from T15 minutes to T245 minutes

Eligibility
Key inclusion criteria
Provision of informed consent
Female 
Aged 18­-40 years
BMI 18.5 - 24.9 kg/m2
Self­ reported healthy
Combined monophasic oral contraceptive pill use for >3 months
Self-reported with regular menses.
Minimum age
18 Years
Maximum age
40 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Pregnancy or breastfeeding
History of chronic disease
Use of any medication other than the oral contraceptive pill during the last 3 months
Vegetarian
Claustrophobia

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
A sample size of n=16 was determined to be necessary to detect a significant change (0.5mmol/L) in blood glucose (primary variable) and a within-participant variance in blood glucose of 0.4 mmol/L (SD). The sample size will be increased to n=18 to allow for possible dropouts.
Please see: http://hedwig.mgh.harvard.edu/sample_size/js/js_crossover_quant.html
The sample size provides good power to detect differences in energy expenditure (other primary variable) - 8 participants would be required to detect a 5% increase in energy expenditure between contraceptive pill phases, with a standard deviation of 0.05 kcal/min.

Outcome variables will be assessed using a variety of statistical methods including repeated measures ANOVA, Pearson's correlation testing, and mixed-model linear regression analyses.

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 10403 0
New Zealand
State/province [1] 10403 0
Auckland

Funding & Sponsors
Funding source category [1] 299462 0
Government body
Name [1] 299462 0
Health Research Council
Address [1] 299462 0
PO Box 5541,
Wellesley Street,
Auckland 1141
Country [1] 299462 0
New Zealand
Primary sponsor type
Individual
Name
Dr Jennifer Miles-Chan
Address
Senior Lecturer
School of Biological Sciences
University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142

Country
New Zealand
Secondary sponsor category [1] 298760 0
University
Name [1] 298760 0
University of Auckland Research Office
Address [1] 298760 0
Level 10, Building 620,
Symonds Street,
Auckland 1010
Country [1] 298760 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300368 0
Health and Disabilities Ethics Committees (Northern A Committee)
Ethics committee address [1] 300368 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 300368 0
New Zealand
Date submitted for ethics approval [1] 300368 0
13/04/2018
Approval date [1] 300368 0
10/05/2018
Ethics approval number [1] 300368 0
18/NTA/61

Summary
Brief summary
The prevalence of cardiometabolic disease is increasing worldwide, and particularly
amongst young women. Furthermore, the risk posed by these diseases appears to
differ between the sexes, with type 2 diabetes conferring higher risk cardiovascular related
mortality in women. However our understanding of how sex hormone status
influences glucose handling is limited. Moreover, despite decades of consumption,
surprisingly little conclusive research has been conducted on the effects of
exogenous sex hormones (such as those contained within the oral contraceptive pill)
on this relationship.

This project will shed light on the relationship between exogenous hormones and
glucose handling by examining the acute effects that oral contraceptives have on
glucose homeostasis and metabolic profile in women of child bearing age. Oral
contraceptives are known to regulate the menstrual cycle by the use of exogenous
hormones, containing 21 days of active (hormonal) pills, and 7 days of inactive
(placebo) pills. This study will recruit 18 women on the combined oral contraceptive
pill. The women will be between 20 and 40 years of age, and have a “normal” BMI
(18.5 -24.9 kgm-2). These women will undergo testing at the end of both the hormonal
pill phase and the inactive pill phase to determine whether there are differences in
glucose homeostasis and metabolic profile as a result of exogenous hormone use.
An oral glucose tolerance test will be conducted during each phase, along with
concomitant monitoring of energy expenditure and substrate utilisation (by indirect
calorimetry), body temperature, and metabolic profiling in blood.
The results gained from this study will be of importance not only to our understanding
of the relationship between the combined oral contraceptive pill on glucose
homeostasis, but also in terms of the optimisation of standards of care for treatment
of diabetes, with the ultimate aim of tailoring diabetes treatment/prevention strategies
in accordance with hormonal status to their efficacy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83430 0
Dr Jennifer Miles-Chan
Address 83430 0
Senior Lecturer
School of Biological Sciences
University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
Country 83430 0
New Zealand
Phone 83430 0
+64 9 9234322
Fax 83430 0
Email 83430 0
j.miles-chan@auckland.ac.nz
Contact person for public queries
Name 83431 0
Dr Jennifer Miles-Chan
Address 83431 0
Senior Lecturer
School of Biological Sciences
University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
Country 83431 0
New Zealand
Phone 83431 0
+64 9 9234322
Fax 83431 0
Email 83431 0
j.miles-chan@auckland.ac.nz
Contact person for scientific queries
Name 83432 0
Dr Jennifer Miles-Chan
Address 83432 0
Senior Lecturer
School of Biological Sciences
University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
Country 83432 0
New Zealand
Phone 83432 0
+64 9 9234322
Fax 83432 0
Email 83432 0
j.miles-chan@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All individual participant data collected during the trial, after de-identification, underlying published results only.
When will data be available (start and end dates)?
Availability of the above data will start immediately post-publication. No end date is yet determined.
Available to whom?
Case-by-case basis at the discretion of the primary sponsor.
Available for what types of analyses?
Only to achieve aims in the approved proposal.
How or where can data be obtained?
Access subject to approvals by the primary sponsor, with a requirement to sign approved access
agreement. Dr Jennifer Miles-Chan, the primary sponsor, can be contacted on j.mileschan@
auckland.ac.nz or +64 9 923 4322
What supporting documents are/will be available?
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 7286 0
Informed consent form
Citation [1] 7286 0
Link [1] 7286 0
Email [1] 7286 0
j.miles-chan@auckland.ac.nz
Other [1] 7286 0
Attachment [1] 7286 0
Type [2] 7287 0
Ethical approval
Citation [2] 7287 0
Link [2] 7287 0
Email [2] 7287 0
j.miles-chan@auckland.ac.nz
Other [2] 7287 0
Attachment [2] 7287 0
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary