Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000074796
Ethics application status
Not yet submitted
Date submitted
17/01/2013
Date registered
21/01/2013
Date last updated
11/03/2021
Date data sharing statement initially provided
11/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
High intensity intermittent training in Polycystic Ovary Syndrome: A randomised control trial to evaluate clinical and mechanistic improvements in metabolic health.
Scientific title
A randomized control trial comparing the benefits of high intensity intermittent training (HIIT) to current physical activity guidelines minimum exercise recommendations, when integrated with a behavioural lifestyle change intervention, on metabolic, reproductive and psychological health, and sustained exercise engagement in overweight women with Polycystic Ovary Syndrome
Secondary ID [1] 281792 0
Nil
Universal Trial Number (UTN)
U1111-1138-6077
Trial acronym
PCOSHIIE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Polycystic Ovary Syndrome
 288116 0
Insulin Resistance
 288131 0
Obesity 288132 0
Menstrual disturbances and ovulation
 288133 0
Depression
 288134 0
Anxiety
 288135 0
Polycystic Ovary Syndrome Health related quality of life
 288136 0
Barriers and Facilitators to physical activity and lifestyle
288137 0
Condition category
Condition code
Metabolic and Endocrine 288491 288491 0 0
Other metabolic disorders
Reproductive Health and Childbirth 288492 288492 0 0
Other reproductive health and childbirth disorders
Mental Health 288493 288493 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Women will be randomized into the control and 2 exercise intervention groups. Prior to the exercise intervention phase women in both groups will undertake a behavioural lifestyle intervention: an adapted, evidence-based lifestyle behavioural intervention will be provided to all participants to i) ensure exercise is provided in context of combined behavioural and dietary intervention as per guideline recommendations ii) to optimise retention, engagement, motivation and sustainability of exercise. This program and includes provision of healthy eating advice and health promotion behaviour change principles resulting in improved retention (~10% attrition rates in 3 large prior RCT’s compared to standard ~30% dropout rates). This involves 3 x 1 hour group sessions (1 session per week over 3 weeks) focused on diet information and behavioural modification techniques based on social cognitive theory including goal setting, self-monitoring, social support, coping strategies, problem solving and relapse prevention . Non-prescriptive and non-individualised dietary advice is provided consistent with the Australian Dietary and Healthy Eating Guidelines with a focus on healthy food choices, reducing intake of energy-dense and non-core foods and increasing intake of low energy-dense foods. These sessions encourage physical activity (low intensity exercise for 150 minutes/week) but do not include structured exercise. Lifestyle sessions will be provided by trained exercise physiologists.

Exercise interventions (24 weeks): All exercise sessions will be undertaken on cycle ergometers at either Monash University, Victoria University or University of South Australia fitness centres under the supervision of exercise physiologists, who have trained hundreds of overweight & PCOS women. The standard exercise (SE) intervention group is designed to meet the Australian National Physical Activity guidelines of 150 min of exercise per week, while the high-intensity interval exercise group (HIIE) will be matched for weekly energy expenditure.

Standard exercise group(SE)- In addition to behavioural intervention participants will perform 3 supervised low-moderate intensity cycling sessions of 50 minutes at 65-75% of maximal aerobic exercise capacity (using heart rates) per week. This is based on current national and international physical activity guidelines. Exercise sessions will be progressed and adjusted fortnightly to account for individuals exercise capacity and training adaptations.

High intensity intermittent group (HIIE; energy expenditure equivalent to SE-exercise group): In addition to behavioural intervention participants will perform 3 sessions of supervised HIIE cycling sessions/ week. The HIIE sessions entails completing 8-12 x 1min bouts of exercise at 95-100% maximal aerobic capacity (using heart rate) with 1min recovery. HIIE cycling sessions will be progressed and adjusted according to individual capabilities to prevent injury and account for training adaptations. .
Isocaloric balance of HIIE and SE interventions: With cycle ergometry we can determine work done (energy expended)/session and which we will compliment energy expenditure determined from heart rate monitors (Polar [Trademark]) and accelerometers to match work done between groups.
Intervention code [1] 286336 0
Lifestyle
Intervention code [2] 286348 0
Behaviour
Comparator / control treatment
The control group will receive current standard care for women with Polycystic Ovary Syndrome which includes general dietary and exercise advise and undertake the behavioural lifestyle intervention described above Whilst the program has successfully prevented weight gain and has been sustainable, improvements in exercise engagement have been limited. Hence, we do not expect our control group to engage in significant exercise.
Control group
Active

Outcomes
Primary outcome [1] 288648 0
Insulin sensitivity/glucose tolerance by oral glucose tolerance test (OGTT) and hyperinsulinemic euglycemic clamp (subgroup only)
Timepoint [1] 288648 0
OGTT will be assessed before,12 and 24 weeks of exercise, and at the 1 and 2 year follow-up.
Hyperinsulinemic euglycemic clamp (subgroup only) will be assessed before and after the 24 week exercise intervention
Primary outcome [2] 288649 0
Ovulation status by Anti-Mullarian Hormone (AMH) levels, menstrual diaries and urinary pregnadiols
Timepoint [2] 288649 0
AMH will be assessed will be assessed before,12 and 24 weeks of exercise, and at the 1 and 2 year follow-up.
Menstrual diaries and urinary pregnadiols, will only be assessed before and during the 24 week exercise intervention.
Primary outcome [3] 288650 0
Psychological status and exercise behaviours (Depression, Anxiety, Polycystic Ovary Syndrome specific Quality of Life, Physical activity behaviours) using objective physical ativity measures and intrinsic feedback Fitbit® and assocaited applications and validated questionnaires which include: 1) International Physical activity Questionaire 2) Intrinsic Motivation Inventory 3) Behaviour Regulation in exercise questionaire 4) Feeling Scale 5) Polycystic Ovary Syndrome Quality of Life Questionaire 6) Depression Anxiety Stress Scale
Timepoint [3] 288650 0
Psychogical health and exercise behaviours will be assessed via questionnaires before,12 and 24 weeks of exercise, and at the 1 and 2 year follow-up.
Fitbit® generated physical activity will be recorded from 1 week prior to intervention to the end of the 2 year follow-up. This is achieved remotely via the Fitbit® software platform with centralised data logging.
Secondary outcome [1] 300696 0
Molecular changes in skeletal muscle (sub group only) including exercise induced changes in insulin signalling, lipid storage (especiall diacylglycerides and ceramides) and the associated proteins perilipin 2, 3 and 5, muscle tissue fibrosis (mRNA and protein expression). Additional molecular measures will be undertaken which include epigenetic analysis (DNA methylation) and mitochondrial function changes pending tissue availability and funding.
Timepoint [1] 300696 0
Before and after 24 weeks interventions
Secondary outcome [2] 300697 0
Body composition by CT scan including adominal slices for determining viseral fat changes. Additionally, mid-thigh slices to look at global inter- and intra- tissue fat distrubtion as well as non-fat tissue content.
Timepoint [2] 300697 0
Before and after12 and 24 weeks of intervention
Secondary outcome [3] 300698 0
Liver contrbution to insulin senstivity in PCOS and changes indiced by exercise using glucose tracer (sub group undergoing the hyperinsulinemic euglycemic clamp).
Timepoint [3] 300698 0
before and after 24 weeks of intervention

Eligibility
Key inclusion criteria
Must be diagnosed with Polycystic Ovary Syndrome by Rotterdam criteria as recommended criteria by both the NHMRC approved guideline for managing and treating PCOS and a recent NIH workshop with exclusion of other causes of hyperandrogenism (thyroid and prolactin disorders and non-classical congenital adrenal hyperplasia). The diagnostic criteria Polycystic Ovary syndrome include two of (i) irregular menstrual cycles (<21 or >35 days), (ii) clinical (hirsutism, acne) or biochemical (elevation of at least one circulating ovarian androgen) hyperandrogenism and (iii) Polycystic ovaries on ultrasound .
Must have a BMI>25 m/kg2
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Secondary causes of menstrual disturbance and hyperandrogenism, pregnancy (pregnancy test at baseline), smoking, diabetes, uncontrolled hypertension (>160/100), established CVD, renal impairment and malignancy, clinical depression, those on medications that interfere with end-points (e.g. metformin, anti-hypertensives, lipid-lowering agents and oral contraceptive pill) or >75min/week exercise as this is 50% of recommended activity.

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 responding to advertisements placed in local media publications,notice boards, web pages. Once the participant has responded to the advertisement they will be screened via telephone to establish eligibility. Once meeting the criteria they will be sent an study information pack and informed consent forms, and invited to attend a medical screening session to confirm PCOS diagnosis and check health status. Once eligibility is confirmed and informed consent provided the participant will be randomized into either control standard exercise or high intensity exercise groups using a central 24 hour telephone randomization service at the University of Adelaide.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation procedures used will be a simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation). But Participants will be stratified by age and body mass index (BMI)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Measures of insulin sensitivity and other endpoint data will be log-transformed to avoid the problem of heteroscedasticity. The effects of the treatments will be estimated using linear mixed-model procedures with inclusion of covariates as appropriate to estimate effects of moderators and mediators. Additional intention-to-treat analyses will be undertaken as appropriate. Data analysis will be completed by the in-house biostatistician who has reviewed the study design and sample size.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Other reasons/comments
Other reasons
Important changes to protocol before recruitment commenced
Date of first participant enrolment
Anticipated
1/07/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
177
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC

Funding & Sponsors
Funding source category [1] 286575 0
Self funded/Unfunded
Name [1] 286575 0
Country [1] 286575 0
Australia
Primary sponsor type
University
Name
Victoria University
Address
Cnr Geelong and Ballarat Road
Footscray
Victoria
OR
PO Box 14428
Melbourne
8001
Country
Australia
Secondary sponsor category [1] 285359 0
University
Name [1] 285359 0
Monash University
Address [1] 285359 0
Wellington Road
Clayton
Vic 3008
Country [1] 285359 0
Australia
Other collaborator category [1] 277248 0
University
Name [1] 277248 0
University of Adelaide
Address [1] 277248 0
The University of Adelaide
Adelaide, South Australia
5005
Country [1] 277248 0
Australia
Other collaborator category [2] 277249 0
University
Name [2] 277249 0
University of South Australia
Address [2] 277249 0
University of South Australia
GPO Box 2471
Adelaide,
South Australia 5001
Country [2] 277249 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 288651 0
Monash Health and Monash University Human Research Ethics Committee
Ethics committee address [1] 288651 0
Ethics committee country [1] 288651 0
Australia
Date submitted for ethics approval [1] 288651 0
29/08/2014
Approval date [1] 288651 0
Ethics approval number [1] 288651 0
Ethics committee name [2] 288652 0
Victoria University Human Research Ethics Commitee
Ethics committee address [2] 288652 0
Ethics committee country [2] 288652 0
Australia
Date submitted for ethics approval [2] 288652 0
31/10/2014
Approval date [2] 288652 0
Ethics approval number [2] 288652 0
Ethics committee name [3] 288653 0
University of South Australia Human Research Ethics Commitee
Ethics committee address [3] 288653 0
Ethics committee country [3] 288653 0
Australia
Date submitted for ethics approval [3] 288653 0
31/10/2014
Approval date [3] 288653 0
Ethics approval number [3] 288653 0
Ethics committee name [4] 288654 0
The University of Adelaide Human Research Ethics Committee
Ethics committee address [4] 288654 0
Ethics committee country [4] 288654 0
Australia
Date submitted for ethics approval [4] 288654 0
29/08/2014
Approval date [4] 288654 0
Ethics approval number [4] 288654 0

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

Contacts
Principal investigator
Name 37118 0
A/Prof Nigel Stepto
Address 37118 0
College of Sport and Exercise Science
Victoria University
PO Box 14428
Melbourne VIC
8001
Country 37118 0
Australia
Phone 37118 0
+61 3 9919 5416
Fax 37118 0
Email 37118 0
[email protected]
Contact person for public queries
Name 37119 0
Nigel Stepto
Address 37119 0
College of Sport and Exercise Science
Victoria University
PO Box 14428
Melbourne VIC
8001
Country 37119 0
Australia
Phone 37119 0
+61 3 9919 5416
Fax 37119 0
Email 37119 0
[email protected]
Contact person for scientific queries
Name 37120 0
Nigel Stepto
Address 37120 0
College of Sport and Exercise Science
Victoria University
PO Box 14428
Melbourne VIC
8001
Country 37120 0
Australia
Phone 37120 0
+61 3 9919 5416
Fax 37120 0
Email 37120 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.