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Trial registered on ANZCTR


Registration number
ACTRN12617000400369
Ethics application status
Approved
Date submitted
11/03/2017
Date registered
17/03/2017
Date last updated
12/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
PRT MEDIC: Progressive Resistance Training for MEtabolic Syndrome and Depression Integrated Care
Scientific title
Effect of Progressive Resistance Training on insulin resistance and depression in adults with Metabolic Syndrome and Major Depressive Disorder.
Secondary ID [1] 291427 0
Diabetes Australia Research Reference: Y17G-MAVY
Universal Trial Number (UTN)
Trial acronym
PRT MEDIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 302441 0
Metabolic Syndrome 302442 0
Type 2 Diabetes 302484 0
Condition category
Condition code
Mental Health 302010 302010 0 0
Depression
Metabolic and Endocrine 302011 302011 0 0
Metabolic disorders
Metabolic and Endocrine 302044 302044 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Progressive Resistance Training (PRT).
The PRT intervention will include 8 machine-based/free-weight exercises involving the upper and lower body and the trunk. The intervention will be prescribed with a warm-up set followed by 3 sets of 8 repetitions at 80% of their current capacity.

Participants will train 3 days per week, for 12 weeks. Each session will last approximately 45-60 minutes. Participants will exercise in a University based gymnasium, Participants will be fully supervised throughout the whole intervention period.

Exercises will include leg press, knee extension, knee flexion, chest press, seated row, triceps, hip abduction, and plantar flexion initially. Total session time will be approximately 45 min, with a ratio of no more than 1 trainer for 4 participants. Participants will be progressed continuously throughout the intervention, guided by one repetition maximum (1RM) strength testing every 2 weeks to maintain intensity at least 80% of current maximum capacity.

Participants in this group will also remain under the usual care of their GP for the management of their depression and metabolic syndrome
Intervention code [1] 297464 0
Rehabilitation
Intervention code [2] 297496 0
Treatment: Other
Comparator / control treatment
Participants randomised to the control intervention will be referred to their GP for management of their depression and metabolic syndrome.
Control group
Active

Outcomes
Primary outcome [1] 301437 0
Homeostatic Model of Assessment 2 - Insulin Resistance (HOMA2-IR)
Calculated from fasting serum glucose and serum c-peptide
Timepoint [1] 301437 0
Baseline and 12 weeks
Primary outcome [2] 301439 0
Self rated symptoms of depression
- Patient Health Questionnaire 9
- Center for Epidemiologic Studies Depression Scale
Timepoint [2] 301439 0
Baseline and 12 weeks
Primary outcome [3] 301441 0
Therapist-rated depressive symptoms using the Hamilton Depression Rating Scale (HDRS) and the Mini International Neuropsychiatric Interview (MINI) for depression
Timepoint [3] 301441 0
Baseline and 12 weeks
Secondary outcome [1] 332646 0
Cognitive function using NIH toolbox app, administered using an iPad.
Timepoint [1] 332646 0
Baseline and 12 weeks
Secondary outcome [2] 332647 0
Cognitive function; Trail making test A and B
Timepoint [2] 332647 0
Baseline and 12 weeks
Secondary outcome [3] 332648 0
Hamilton Anxiety Rating Scale
Timepoint [3] 332648 0
Baseline and 12 weeks
Secondary outcome [4] 332649 0
Beck Anxiety Inventory
Timepoint [4] 332649 0
Baseline and 12 weeks
Secondary outcome [5] 332650 0
Oxford Happiness Scale
Timepoint [5] 332650 0
Baseline and 12 weeks
Secondary outcome [6] 332651 0
Positive And Negative Affect Scale (PANAS)
Timepoint [6] 332651 0
Baseline and 12 weeks
Secondary outcome [7] 332653 0
Maximal strength assessed using one-repetition maximum (1RM) strength tests
Timepoint [7] 332653 0
Baseline and 12 weeks
Secondary outcome [8] 332654 0
Aerobic capacity using a graded exercise test until voluntary fatigue
Timepoint [8] 332654 0
Baseline and 12 weeks
Secondary outcome [9] 332656 0
Heart Rate Variability, assessed on Sphgmocor XCEL.
Timepoint [9] 332656 0
Baseline and 12 weeks
Secondary outcome [10] 332657 0
Ambulatory blood pressure for 24 hours assessed using Oscar 2 with Sphygmocor Inside
Timepoint [10] 332657 0
Baseline and 12 weeks
Secondary outcome [11] 332658 0
Pittsburgh Sleep Quality Index
Timepoint [11] 332658 0
Baseline and 12 weeks
Secondary outcome [12] 332659 0
Insomnia Severity Index
Timepoint [12] 332659 0
Baseline and 12 weeks
Secondary outcome [13] 332660 0
Objective sleep quality using actigraphy, worn continuously over 7 days.
Timepoint [13] 332660 0
Baseline and 12 weeks
Secondary outcome [14] 332661 0
Objective physical activity using activity monitors (Actigraph) , worn continuously over 7 days.
Timepoint [14] 332661 0
Baseline and 12 weeks
Secondary outcome [15] 332662 0
Physical Activity assessed using the Harvard Alumni Questionnaire
Timepoint [15] 332662 0
Baseline and 12 weeks
Secondary outcome [16] 332663 0
3 day food record. The record will include 2 weekdays and 1 weekend day.
Timepoint [16] 332663 0
Baseline and 12 weeks
Secondary outcome [17] 332664 0
Body Composition assessed using Dual Energy X-Ray Absorptiometry
Timepoint [17] 332664 0
Baseline and 12 weeks
Secondary outcome [18] 332665 0
Waist Circumference using the International Diabetes Federation protocol
Timepoint [18] 332665 0
Baseline and 12 weeks
Secondary outcome [19] 332666 0
Oral Glucose Tolerance Test
- Serum glucose at 0, 30, 60, 90 and 120 minutes
Timepoint [19] 332666 0
Baseline and 12 weeks
Secondary outcome [20] 332741 0
Oral Glucose Tolerance Test
- Serum insulin at 0, 30, 60, 90 and 120 minutes
Timepoint [20] 332741 0
Baseline and 12 weeks
Secondary outcome [21] 332742 0
Physical Activity using the Physical Activity Scale for the Elderly
Timepoint [21] 332742 0
Baseline and 12 weeks
Secondary outcome [22] 332743 0
Pulse Wave Analysis using Sphygmocor XCEL
Timepoint [22] 332743 0
Baseline and 12 weeks
Secondary outcome [23] 332744 0
Pulse Wave Velocity using Sphygmocor XCEL
Timepoint [23] 332744 0
Baseline and 12 weeks
Secondary outcome [24] 332745 0
Fasting blood test - serum cortisol
Timepoint [24] 332745 0
Baseline and 12 weeks
Secondary outcome [25] 332746 0
Fasting blood test - serum C-reactive protein
Timepoint [25] 332746 0
Baseline and 12 weeks
Secondary outcome [26] 332747 0
Fasting blood test - Serum cholesterol
Timepoint [26] 332747 0
Baseline and 12 weeks
Secondary outcome [27] 332748 0
Fasting blood test - serum HDL
Timepoint [27] 332748 0
Baseline and 12 weeks
Secondary outcome [28] 332749 0
Fasting blood test - serum LDL
Timepoint [28] 332749 0
Baseline and 12 weeks
Secondary outcome [29] 332750 0
Fasting blood test - serum triglycerides
Timepoint [29] 332750 0
Baseline and 12 weeks
Secondary outcome [30] 332751 0
Blood Test - Glycated haemoglobin (HbA1c)
Timepoint [30] 332751 0
Baseline and 12 weeks
Secondary outcome [31] 336142 0
Core self evaluation quesstionnaire
Timepoint [31] 336142 0
Baseline

Eligibility
Key inclusion criteria
1. Major Depressive Disorder according to DSM 5 criteria,
*If not receiving any treatment; PHQ-9 of 10 or higher (moderate depression)
*If receiving treatment, PHQ-9 of 5 or higher (mild depression)
2. Metabolic syndrome according to IDF criteria
*Central obesity (Waist circumference Men; greater than or equal to 94 cm men. Women; greater than or equal to 80 cm) and any 2 of the following:
*Raised triglycerides (150 mg/dL (1.7 mmol/L) or higher, or specific treatment for this lipid abnormality)
*Low HDL cholesterol (Less than 40 mg/dL (1.03 mmol/L) in men and less than 50 mg/dL (1.29 mmol/L) in women or specific treatment for this lipid abnormality
*Hypertension (systolic BP of 130 or higher, or diastolic BP of 85 mm Hg or higher, or treatment of previously diagnosed hypertension)
*High fasting plasma glucose ((FPG) of 100 mg/dL (5.6 mmol/L) or higher.

3. at least 40 years of age
4. Not on oral hypoglycaemics or insulin therapy
5. No diagnosis of type 2 diabetes, or not found to have type 2 diabetes during the screening process
6. Sedentary - less than 150 minutes per week of structured moderate or vigorous physical activity.
7. No terminal or rapidly progressing illness, or condition that precludes participation in progressive resistance training


Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Type 2 diabetes or use of oral hypoglycaemic medication or insulin
Suicide ideation
Illegal drug use
Alcohol dependence/abuse (3 or 4 on CAGE questionnaire)
Substance abuse disorder

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)
Randomisation will occur by contacting the holder of the allocation schedule who is at central administration site and not otherwise involved with the study
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
We will use a concealed, computer-generated sequence (www.randomization.com) of randomly permuted variable blocks, stratified by sex, age (40-59; 60+) and current treatment for depression (yes/no). Randomisation will occur at the completion of the baseline assessment.
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
An intention-to-treat analytic strategy will be utilised, inclusive of all participants randomised, regardless of dropout. All outcomes will be analysed using linear mixed effects models with repeated measures. Main effects of PRT, TIME and PRTxTIME will be entered, and models adjusted for covariates selected a priori (age, sex, treatment for major depressive disorder) as well as additional confounders associated with the dependent variable of interest. Significance will be set at a=0.05 for primary and pre-specified secondary outcomes, with unspecified outcomes undergoing Bonferroni adjustment.

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] 15571 0
2141 - Lidcombe

Funding & Sponsors
Funding source category [1] 295895 0
Charities/Societies/Foundations
Name [1] 295895 0
Diabetes Australia Research Trust
Address [1] 295895 0
PO Box 3156
Canberra ACT 2601
Country [1] 295895 0
Australia
Primary sponsor type
Individual
Name
Dr Yorgi Mavros
Address
K214
University of Sydney, Cumberland Campus
75 East Street,
Lidcombe NSW 2141
Country
Australia
Secondary sponsor category [1] 294766 0
Individual
Name [1] 294766 0
Professor Maria Fiatarone Singh
Address [1] 294766 0
University of Sydney, Cumberland Campus
K221, 75 East Street
Lidcombe NSW 2141
Country [1] 294766 0
Australia
Secondary sponsor category [2] 294768 0
Individual
Name [2] 294768 0
Professor Sharon Naismith
Address [2] 294768 0
The Brain and Mind Centre
94-100 Mallett Street
M02F, Camperdown, NSW 2050
Country [2] 294768 0
Australia
Secondary sponsor category [3] 294769 0
Individual
Name [3] 294769 0
Professor Ian Caterson
Address [3] 294769 0
Level 2 Charles Perkins Centre D17
Johns Hopkins Drive (off Missenden Road)
The University of Sydney
Camperdown NSW 2006
Country [3] 294769 0
Australia
Secondary sponsor category [4] 294770 0
Individual
Name [4] 294770 0
Professor David Celermajer
Address [4] 294770 0
Department of Cardiology
RPA Hospital
Missenden Rd.,
Camperdown NSW 2050
Country [4] 294770 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297174 0
University of Sydney Human Research Ethics Committee
Ethics committee address [1] 297174 0
Research Integrity & Ethics Administration
Research Portfolio
Level 2, Margaret Telfer Building (K07)
The University of Sydney
NSW 2006 Australia
Ethics committee country [1] 297174 0
Australia
Date submitted for ethics approval [1] 297174 0
16/01/2017
Approval date [1] 297174 0
07/03/2017
Ethics approval number [1] 297174 0
2017/066

Summary
Brief summary
Individuals with depression and metabolic syndrome are 6.6 times more likely to develop type 2 diabetes within 5 years compared to individuals without either condition. Thus, early, robust and targeted interventions are warranted to alleviate symptoms of depression and improve the metabolic health of these at-risk individuals.
The primary aims of this project are to determine the effects of progressive resistance training on insulin resistance (measured using the Homeostatic Model of Assessment-2) and depressive symptoms [assessor-rated Hamilton Depression Rating Scale (HDRS), Patient Health Questionnaire (PHQ-9) and Center for Epidemiologic Studies Depression Scale (CES-D) in adults with co-existing metabolic syndrome and major depressive disorder. Participants will be randomized to receive either progressive resistance training (PRT), 3 days per week for 12 weeks in addition to usual care from their GP, or referred to their GP for usual care. Participants randomised to the control intervention will be referred to their GP for management of their depression and metabolic syndrome. Blinded assessments will occur pre, and post intervention.

This will be the first trial of PRT for individuals with co-existing major depressive disorder, metabolic syndrome and impaired glucose tolerance, and only the 5th trial of PRT in clinical depression.

Primary Hypotheses
1. 12 weeks of PRT will significantly reduce insulin resistance, measured via Homeostatic Model of Assessment-2 (HOMA2-IR) compared to controls referred for General Practitioner (GP) care.
2. 12 weeks of PRT will significantly improve therapist-rated depressive symptoms [Hamilton Depression Rating Scale (HDRS)] as well as self-rated symptoms [Patient Health Questionnaire (PHQ-9)] and Center for Epidemiologic Studies Depression Scale (CES-D) compared to controls referred for GP care.

Secondary Hypotheses
1. 12 weeks of PRT will significantly reduce glucose and insulin area under the curve during an oral glucose tolerance test (OGTT) compared to controls referred for GP care.
2. 12 weeks of PRT will significantly reduce glycated haemoglobin (HbA1c) compared to controls referred for GP care.
3. 12 weeks of PRT will significantly increase lean body mass (LBM) and decrease central adiposity compared to controls referred for GP care.
4. 12 weeks of PRT sill significantly improve central haemodynamics compared to controls referred for GP care.
4. Reductions in depressive symptoms will be associated with reductions in HOMA2-IR.
5. Improvements in body composition (increases in lean tissue and reductions in central adiposity), and reductions in systemic inflammation and serum cortisol will be independently associated with improvements in metabolic profile and depressive symptoms.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73234 0
Dr Yorgi Mavros
Address 73234 0
University of Sydney, Cumberland Campus
K214, 75 East Street
Lidcombe NSW 2141
Country 73234 0
Australia
Phone 73234 0
+61 02 9351 9279
Fax 73234 0
Email 73234 0
yorgi.mavros@sydney.edu.au
Contact person for public queries
Name 73235 0
Dr Yorgi Mavros
Address 73235 0
University of Sydney, Cumberland Campus
K214, 75 East Street
Lidcombe NSW 2141
Country 73235 0
Australia
Phone 73235 0
+61 02 9351 9279
Fax 73235 0
Email 73235 0
yorgi.mavros@sydney.edu.au
Contact person for scientific queries
Name 73236 0
Dr Yorgi Mavros
Address 73236 0
University of Sydney, Cumberland Campus
K214, 75 East Street
Lidcombe NSW 2141
Country 73236 0
Australia
Phone 73236 0
+61 02 9351 9279
Fax 73236 0
Email 73236 0
yorgi.mavros@sydney.edu.au

No data has been provided for results reporting
Summary results
Not applicable