Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001689864
Ethics application status
Approved
Date submitted
8/11/2021
Date registered
10/12/2021
Date last updated
10/12/2021
Date data sharing statement initially provided
10/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
UPLIFT: Progressive Resistance Training (PRT) as Adjunctive Treatment for Alcohol Use Disorder (AUD)
Scientific title
Progressive Resistance Training as an Adjunct Treatment for Alcohol Use Disorder
Secondary ID [1] 305713 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alcohol use disorder (AUD) 324179 0
Mental illness (co-morbidity) 324180 0
Condition category
Condition code
Mental Health 321653 321653 0 0
Addiction
Mental Health 321654 321654 0 0
Depression
Mental Health 321655 321655 0 0
Anxiety
Mental Health 321656 321656 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Interventional
Description of intervention(s) / exposure 1.Brief Name: High intensity progressive resistance training (PRT) in addition to usual care (please see description of usual care received by the control group).
2.Rationale: PRT or strength training has been reported as the preferred modality of exercise by individuals undergoing substance abuse treatment (Abrantes et al, 2011). To date, only one study of high intensity PRT has been published, and it was found to be superior to aerobic exercise and moderate intensity resistance training (circuit training) in reducing depressive symptoms during rehabilitation for alcohol and substance abuse (Palmer et al, 1995). This is in agreement with the known anti-depressant effects of PRT (Gordon et al, 2018; Cooney et al, 2013; Herring et al, 2012; Singh et al, 2005). However, the effect of PRT on alcohol dependency itself are currently unknown, and so PRT presents a novel and innovative therapy that warrants testing in appropriately designed studies.
3. Materials: Free-weights and Digital K400 Keiser pneumatic resistance machines (Keiser Sports health Equipments, Inc. Fresno, CA)
4. PRT Protocol: The intervention period is 12 weeks in duration and training will be 3 times per week for approximately 45-60 minutes. Week 1 of the intervention will include familiarisation and gradual increase in target intensity from 50%, 60%, 70% 1RM in each successive session. From the first session of week 2, training intensity will be set at 80% 1RM and progressed by a projected gain in strength of 3% 1RM each session, used in conjunction with the Borg Rating of Perceived Exertion Scale. At the start of every 7th session, 1RM will be re-tested and target weight at 80% 1RM will be recalculated based on the new 1RM. Total training volume is 24 repetitions per exercise, set initially at 3 sets of 8 repetitions. However, as intensity is most important, sets and repetitions may be manipulated such that prescribed intensity is adhered to and the total volume remains 24 repetitions per exercise. In addition, assessor observation of pain, accessory muscle use or violations of form will be used to titrate the load. Eight resistance machines will be used and exercises will be completed in the following order; leg press, seated row, knee extension, chest press, knee flexion, tricep pushdown, lateral raises and plantar flexion initially. There will be 2-3 minutes rest between sets to allow sufficient recovery of anaerobic metabolism.
5. Supervision: Subjects will be trained by an exercise physiologist accredited by Exercise and Sport Science Australia in a supervised setting at a ratio of 1 trainer for 4-5 subjects
6. Mode of delivery: Every training session will be supervised face to face.
7. Location: Once patients are discharged into the outpatient program, participants randomly assigned to the intervention group will commence their training at the Faculty of Health Science, Cumberland Campus of the University of Sydney in Lidcombe NSW Australia.
8. Frequency: Participants will train 3 days of the week on non-consecutive days over the 12-week intervention period.
9. Adherence: Session adherence and compliance to the exercise prescription will also be monitored and recorded. Participants will be contacted following any missed sessions, to discuss reasons for absence and to encourage their attendance at subsequent training sessions.

Abrantes, A.M., Battle, C.L., Strong, D.R., Ing, E., Dubreuil, M.E., Gordon, A., & Brown, R.A.(2011). Exercise preferences of patients in substance abuse treatment. Mental Health and Physical Activity, 4(2), 79-87.

Cooney, GM., Dwan, K., Greig, CA., Lawlor, DA., Rimer, J., Waugh, FR., & McMurdo, M. (2013). Exercise for depression. Cochrane Database of Systematic Reviews, (9) Cd004366.

Gordon, BR., McDowell, CP., Hallgren, M., Meyer, JD., Lyons, M., & Herring, MP. (2018). Association of Efficacy of Resistance Exercise Training With Depressive Symptoms: Meta-analysis and Meta-regression Analysis of Randomized Clinical Trials. JAMA Psychiatry, 75(6), 566-576

Herring, MP., Puetz, TW., O’Connor, PJ., & Dishman, RK. (2012). Effect of exercise training on depressive symptoms among patients with a chronic illness: a systematic review and meta-analysis of randomized controlled trials. JAMA Internal Medicine, 172(2), 101-111

Palmer, J.A., Palmer, L.K., Michiels, K., & Thigpen, B. (1995). Effects of type of exercise on depression in recovering substance abusers. Perceptual and Motor Skills, 80, 523-530.

Singh, N.A., Stavrinos, T.M., Scarbek, Y., Galambos, G., Liber, C., & Fiatarone Singh, MA. (2005). A randomized controlled trial of high versus low intensity weight training versus general practitioner care for clinical depression in older adults. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 60(6):768-776.
Intervention code [1] 322098 0
Rehabilitation
Comparator / control treatment
The control group will receive usual care provided by SJoGH within the Alcohol, Drugs and Addictive behaviours outpatient program. The 12-week outpatient program for weekly sessions held on hospital grounds. No structured or supervised exercise will be provided to participants randomised to the control group.
Control group
Active

Outcomes
Primary outcome [1] 329432 0
The number of alcoholic drinks consumed per week, measured using the Timeline Followback method 7-day recall.
Timepoint [1] 329432 0
The baseline assessment will capture alcohol consumption (grams/week) for the first seven days after the patient has been discharged from the hospital. The baseline outcome measurement must be captured by 22 days post discharge.

The follow-up assessment of alcohol consumption (grams/week) will capture the 12th week after randomisation into either the intervention group or the usual care group. This will capture days 77 to 84 postrandomisation. There will be a 4-week window to capture the follow-up assessment of the alcohol consumption..
Secondary outcome [1] 402571 0
Therapist-rated depressive symptoms assessed using the Hamilton Depression Rating Scale for Depression (HAM-D).
Timepoint [1] 402571 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [2] 402572 0
Therapist-rated anxiety symptoms measured using the Hamilton Anxiety Rating Scale-A (HAM-A).
Timepoint [2] 402572 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [3] 402573 0
Sleep quality measured via the Pittsburgh Sleep Quality Index (PSQI)
Timepoint [3] 402573 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [4] 402574 0
Sleep quality - Insomnia severity scale (ISS)
Timepoint [4] 402574 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [5] 402575 0
Functional capacity assessed via a 6-minute walk test.
Timepoint [5] 402575 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [6] 402578 0
Body weight using digital scales
Timepoint [6] 402578 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [7] 402579 0
Waist circumference using Lufkin anthropometry tape-measure, following International Diabetes Federation protocol
Timepoint [7] 402579 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [8] 402580 0
Physical activity levels, measured via using the Havard Alumni Questionnaire 7-¬day recall.
Timepoint [8] 402580 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [9] 402581 0
Alcohol dependency, measured via the Short Alcohol Dependence Data (SADD) questionnaire
Timepoint [9] 402581 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [10] 402583 0
The Penn Alcohol Craving Scale (PACS) measures the frequency, intensity, and duration of craving, the ability to resist drinking, and overall craving levels across 7 days.
Timepoint [10] 402583 0
The baseline assessment of cravings will be completed 7 days after discharge into the outpatient program (to capture the previous 7 days), and post 12 weeks of exercise training or control condition.
Secondary outcome [11] 402584 0
Trails A and B is a neuropsychological test. Cognitive functions assessed include attention, visual search and scanning, sequencing and shifting, psychomotor speed, abstraction, flexibility, and the ability to maintain two trains of thought simultaneously. [1-2]

1. Lezak MD, Howieson DB, Loring DW. Neuropsychological Assessment. 4. Oxford University Press; New York, NY: 2004.

2. Strauss E, Sherman EMS, Spreen O. A compendium of neuropsychological tests: Administration, norms, and commentary. 3. Oxford University Press; New York, NY: 2006.
Timepoint [11] 402584 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [12] 402586 0
Cognitive function - Symbol Digit Modalities Test (SDMT)
Timepoint [12] 402586 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [13] 402587 0
Cognitive function - Montreal Cognitive Assessment (MoCA)
Timepoint [13] 402587 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [14] 402588 0
Blood Pressure using a digital sphygmomanometer (Suntech). Measurements will be taken in a fasted state after lying in a supine position for 10 minutes.
Timepoint [14] 402588 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [15] 402589 0
Pulse Wave Velocity (PWV) obtained using the SphygmoCor Unit and SphygmoCor software.
Timepoint [15] 402589 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [16] 402590 0
Heart rate variability obtained using the SphygmoCor Unit and SphygmoCor software.
Timepoint [16] 402590 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [17] 402591 0
Pulse Wave Analysis (PWA) obtained using the SphygmoCor Unit and SphygmoCor software
Timepoint [17] 402591 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [18] 402592 0
Self-rated depression symptoms [Patient Health Questionnaire (PHQ-9)].
Timepoint [18] 402592 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [19] 402593 0
Self-reported anxiety symptoms measured using the Generalised Anxiety Disorder-7 questionnaire (GAD-7)].
Timepoint [19] 402593 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [20] 403887 0
One-repetition maximum (1RM) - Leg press.
Performed using Digital K400 Keiser pneumatic resistance machines (Keiser Sports health Equipments, Inc. Fresno, CA).
Timepoint [20] 403887 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [21] 403888 0
One-repetition maximum (1RM) - Chest press.
Performed using Digital K400 Keiser pneumatic resistance machines (Keiser Sports health Equipments, Inc. Fresno, CA).
Timepoint [21] 403888 0
Baseline, post 12 weeks of exercise training or control condition.
Secondary outcome [22] 403889 0
One-repetition maximum (1RM) - Knee extension
Performed using Digital K400 Keiser pneumatic resistance machines (Keiser Sports health Equipments, Inc. Fresno, CA).
Timepoint [22] 403889 0
Baseline, post 12 weeks of exercise training or control condition.

Eligibility
Key inclusion criteria
We will recruit men and women, aged 18+, admitted to St John of God (Burwood) hospital, for treatment of an alcohol use disorder. Participants must also have a current co-morbid mental health condition (other than active psychosis). This will be confirmed in one of the following ways:
- Identified when auditing medical records at St John of God Hospital.
- Current pharmacological treatment for a mental health condition identified when auditing medical records,
- Confirmed by general practitioner or psychiatrist.
Individuals who do not satisfy either of the criteria above, may be eligible for inclusion based on a score of greater than 10 on the PHQ-9 (major depressive disorder) or a score greater than 10 on the GAD-7 (anxiety). Diagnosis of depression or anxiety will be confirmed by the study physician. Participants must have completed acute withdrawal treatment for the alcohol or any other substance they have been using before they are approached for recruitment. Participants must have the capacity to consent (assessed by SJoGH admitting staff), competency in English sufficient for assessment and training, and clearance from the study physician to exercise.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded from participation in the study if they present with active suicidal ideation, active psychosis, delirium, dementia, acute withdrawal, unstable cardiovascular disease, unrepaired aortic aneurysm, rapidly progressive or terminal illness and other conditions that would preclude participation in an exercise trial or require urgent psychiatric referral. Participants who are performing greater than 150 minutes per week of moderate intensity or greater intensity planned exercise of any kind, will also be excluded from participation.

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)
A concealed, computer-generation sequence (www.randomization.com) will be used. The randomisation sequence will be generated by a research assistant not involved in assessments or training and will prepare sequential, opaque sealed envelopes. Randomisation will occur once the baseline assessment has been completed.
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). Randomisation will occur at the completion of the baseline assessment. Randomisation will occur in unequal group sizes of 2:1 (intervention to control group), and random blocks of 3 and 6, and will be stratified by age (18-49, 50+) and sex.
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 used, allowing inclusion of all participants regardless of adherence or dropout without need for imputation. A linear mixed model will be used to assess the main effects of changes over time and group x time interactions, adjusted for age, gender, and time since discharge. Other covariates will be identified by association with the primary outcome.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21010 0
St John of God Hospital - Burwood
Recruitment postcode(s) [1] 35844 0
2134 - Burwood

Funding & Sponsors
Funding source category [1] 310070 0
University
Name [1] 310070 0
2018 UNSW Sydney - University of Sydney Seed Funding Scheme: Mental Health, Drug and Alcohol Comorbidity
Country [1] 310070 0
Australia
Funding source category [2] 310314 0
University
Name [2] 310314 0
2018 UNSW Sydney - University of Sydney Seed Funding Scheme: Mental Health, Drug and Alcohol Comorbidity
Country [2] 310314 0
Australia
Primary sponsor type
University
Name
the University of Sydney
Address
The University of Sydney
Sydney, NSW 2006
Australia
Country
Australia
Secondary sponsor category [1] 311122 0
None
Name [1] 311122 0
Address [1] 311122 0
Country [1] 311122 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309762 0
St John of God Health Care Human Research Ethics Committee
Ethics committee address [1] 309762 0
12 Salvado Road,
SUBIACO,
Western Australia, 6008
Ethics committee country [1] 309762 0
Australia
Date submitted for ethics approval [1] 309762 0
12/06/2018
Approval date [1] 309762 0
11/07/2018
Ethics approval number [1] 309762 0
1411

Summary
Brief summary
The primary aims of this project are to determine the effects of high intensity progressive resistance training (PRT) on the number of alcoholic drinks consumed per week, measured using a 7-day recall in adults who have undergone rehabilitation for alcohol use disorder with mental health comorbidities. Participants will be randomised to receive either PRT, 3 days per week for 12 weeks after discharge into the outpatient program in addition to usual care provided in the outpatient program at St John of God (Burwood) Hospital, or usual care in the outpatient program only at St John of God (Burwood) Hospital. Participants randomised to the control intervention will receive usual care in the 12-week Alcohol, Drugs and Addictive Behaviours outpatient program at St John of God (Burwood) Hospital. We will not advise on treatment. Blinded assessments will occur pre-, and post intervention.
Unequal randomisation will be used to minimise drop-out rates, in a ratio of 2 participants randomised to the intervention group and 1 to the control group. For this trial we have conservatively estimated an effect size of 1.1. With a beta 0.8 and alpha of 0.05, a total of 32 participants will need to be recruited, 11 participants in the control group and 21 in the intervention group, to show significant effects for the number of drinks consumed per week.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115302 0
Dr Yorgi Mavros
Address 115302 0
D18 Susan Wakil Health Building
Western Avenue
The University of Sydney
Camperdown NSW 2006
Country 115302 0
Australia
Phone 115302 0
+61 02 93519279
Fax 115302 0
Email 115302 0
[email protected]
Contact person for public queries
Name 115303 0
Dr Yorgi Mavros
Address 115303 0
D18 Susan Wakil Health Building
Western Avenue
The University of Sydney
Camperdown NSW 2006
Country 115303 0
Australia
Phone 115303 0
+61 02 93519279
Fax 115303 0
Email 115303 0
[email protected]
Contact person for scientific queries
Name 115304 0
Dr Yorgi Mavros
Address 115304 0
D18 Susan Wakil Health Building
Western Avenue
The University of Sydney
Camperdown NSW 2006
Country 115304 0
Australia
Phone 115304 0
+61 02 93519279
Fax 115304 0
Email 115304 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.