ANZCTR - Registration

Registration number

ACTRN12623001279617p

Ethics application status

Submitted, not yet approved

Date submitted

11/11/2023

Date registered

8/12/2023

Date last updated

8/12/2023

Date data sharing statement initially provided

8/12/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Effects of combined arm and leg high-intensity interval training on motor and non-motor symptoms in people with mild to moderate Parkinson's disease:
A randomised controlled feasibility trial

Scientific title

Effects of combined arm and leg high-intensity interval training on motor and non-motor symptoms in people with mild to moderate Parkinson's disease:
A randomised controlled feasibility trial

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

PD_HIIT

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Parkinsons Disease

Condition category

Condition code

Neurological

Parkinson's disease

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

A randomized controlled feasibility trial will be conducted to investigate the effects of high intensity interval training (HIIT) in a novel mode of combined arm and leg ergometry, (Rogue Echo) (Rogue Fitness, Columbus, Ohio, U.S.A), on physiological and functional outcomes in individuals with mild to moderate Parkinsons disease (PD). The trial will run for 8 weeks with 24 (1 hour) sessions in total for the intervention group, excluding 3 baseline assessment sessions and one reassessment session at conclusion of the intervention in both groups. Dose exposure intensities will be individualized from initial baseline maximal oxygen consumption, anaerobic capacity tests and utilizing Borg (6-20) rate of perceived exertion scales. Eighty-five (85) % of mean maximal power obtained during a maximal anaerobic capacity test performed on the Rogue Echo will be used to prescribe the workload intensity during the intervention process. A total of 8 rounds with work to rest ratios of 1:3 minute will be implemented. The intervention will consist of HIIT performed on a specialized cycle ergometer that consists of a normal lower limb cycle that has handles for the upper limbs that the participant push and pulls in a liner motion. Sessions are approximately 1 hour within small groups of participants (1-2). The intervention will be added to usual care. Secondary outcomes will also include adherence to both exercise intensity and modality. This will be assessed by measuring time spent at target workload intensity and adherence to volume and duration of exposure. All assessments and interventions will be implemented face to face at the University of Sydney, Susan Wakil health building research spaces, Camperdown, NSW, Australia. Assessment days will vary from a minimum of two to a maximum of four hours (2-4).
All assessments and interventions will be implemented by accredited exercise physiologists.

Intervention code [1]

Rehabilitation

Intervention code [2]

Treatment: Other

Comparator / control treatment

Usual care
Usual care will be defined as no participation in any form of moderate or high-intensity exercise (aerobic or progressive resistance training) or HIIT. Standard or routine medical or pharmacological management of PD symptoms, medical appointments with health care providers (this may include physiotherapy, occupational therapy and other allied health practitioners excluding new regular structured physical activity), general advisory support (this may include nutritional and hydrational support, mobility support), observational/symptomatic support (Parkinsonian symptom support without addition of new treatment of physical/pharmacological intervention, no change in medication for 3 months).
Usual care physical activity will be defined as any standard exercise regimen (at community exercise facilities or via home-based online platforms), designed to maintain current functional status and capacity. This can include community PD specific classes, generally taught by trained exercise physiologists, physiotherapists, or personal trainers. Other modalities might include balance training, PD warrior classes, yoga, tai chi, Pilates, stretching and flexibility training. These structured exercise sessions must be present before the start of the study, and not newly initiated during the study. Any engagement in these activities will be recorded on the weekly status checks.

Control group

Active

Outcomes

Primary outcome [1]

Habitual gait speed will be measured over a straight path of 4 meters and a 2-meter deceleration lane following the 4-meter path. Participants can use any habitual assistive device if relevant. For the test of habitual gait speed, participants will be asked to walk at their normal and comfortable speed. Tools used will be a stopwatch, tape measure and witches hat cones.

Timepoint [1]

The initial baseline measure will be collected pre intervention on the first day of the assessment process and completion measure will be assessed on the final day of assessments with one week of the end of intervention process. (9 weeks post randomization).

Secondary outcome [1]

Cognitive impairment:
Cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA). The MoCA evaluates multiple cognitive domains including attention, executive function, memory, language, visual constructional skills, conceptual thinking, calculations, and orientation. The tool consists of 13 subsets and yields a total score ranging from 0 to 30, with a high score indicative of better cognitive function. A score below 26 is generally considered to signal cognitive impairment and the assessment is utilised to identify mild cognitive dysfunction and track cognitive changes over time.

Timepoint [1]

The initial baseline measure will be collected pre intervention on the first day of the assessment process and completion measure will be assessed on the final day of assessments with one week of the end of intervention process. (9 weeks post randomization)

Secondary outcome [2]

Brain derived neurotrophic factor and other PD biomarkers will be assessed as a composite secondary outcome. The cytokine and inflammatory markers response to intervention is still in the exploratory phase and be finalized closer to the recruitment stage and after discussion with team members.
Blood samples will be collected from participants for future analysis of specific biomarkers, Brain Derived Neurotrophic Factor (BDNF), alpha synuclein, and other cytokines and inflammatory markers, key indicators in understanding PD progression/response to the exercise intervention.

Timepoint [2]

The initial baseline measure will be collected pre intervention on the first day of the assessment process and completion measure will be assessed on the final day of assessments one week within the end of intervention process. (9 weeks post randomization)

Secondary outcome [3]

Orthostatic blood pressure:
Participants will initially be in a supine position for 5 minutes after which their baseline blood pressure and heart rate will be measured. Subsequently, the participant will stand, and measurements will be repeated at 1- and 3-minutes post standing. Orthostatic blood pressure will be evaluated using a standard sphygmomanometer and stethoscope and any symptoms recorded. A significant drop in systolic pressure (>20mmHg) and diastolic pressure (>10mmHg) upon standing is indicative of orthostatic hypotension. This assessment serves to evaluate cardiovascular responses to postural change.

Timepoint [3]

The initial baseline measure will be collected pre intervention on the first day of the assessment process and completion measure will be assessed on the final day of assessments with one week of the end of intervention process. (9 weeks post randomization).

Secondary outcome [4]

Functional Performance (Short Physical Performance Battery):
Functional performance will be measured by the Short Physical Performance Battery (SPPB). The SPPB measures lower limb function across three domains: static balance, gait speed (inclusive of acceleration phase) and strength. Each subset scores 0-4, with a total of 12 points, a higher score indicating better function.

Timepoint [4]

The initial baseline measure will be collected pre intervention on the first day of the assessment process and completion measure will be assessed on the final day of assessments with one week of the end of intervention process. (9 weeks post randomization).

Secondary outcome [5]

The Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS UPDRS):
The (MDS UPDRS) is a comprehensive tool employed by trained clinicians to evaluate the severity of PD symptoms measuring both motor and non-motor symptoms and is divided into four parts. Researchers will utilise both Part II & Part III only in the assessment process.
1. Non-Motor Experiences of Daily Living: Assesses mental functioning, mood, and social interactions through patient and caregiver questionnaires
2. Motor Experiences of Daily Living: Covers motor aspects during daily activities, based on patient reports and caregiver observations
3. Motor Examination: Performed by a trained clinician, this section measures motor function, such as bradykinesia, rigidity, and tremors
4. Motor Complications: Evaluates medication-related motor fluctuations and dyskinesia

A high score is an indication of greater impairment or more severe symptoms. Each of the four parts of the scale has its own scoring system, and these scores are generally summed to provide a total score that represents the overall severity and impact of the disease on the individual's life. A lower score is generally considered to be better, signifying fewer or less severe symptoms.

Timepoint [5]

The initial baseline measure will be collected pre intervention on the first day of the assessment process and completion measure will be assessed on the final day of assessments with one week of the end of intervention process. (9 weeks post randomization).

Secondary outcome [6]

Maximal oxygen consumption test: (VO2 peak)
An incremental ramp protocol will be conducted on a cycle ergometer with 12-lead electrocardiogram (MGC Diagnostics Corporation, USA), and automated blood pressure cuff measurements (Suntech medical, Morrisville, N.C, USA). Participants will be instructed to aim for an RPM of 50 revolutions/minute. After a 5-minute warm up they will begin the protocol at a predetermined load (Watt/kg body weight). The resistance of the flywheel will be increased so that the workload increases in increments of 10-25 Watts every 60 seconds until the participant reaches a state of volitional fatigue or until other established criteria for maximal effort are met. These may include a plateau in oxygen consumption despite an increasing workload, achieving a heart rate within 10 beats of the predicted maximum for their age, respiratory exchange ratio of >1.1, or a RPE greater than 18/20 (Borg scale). Prior to the onset of the assessment, participants will be familiarised with the Borg (6-20) RPE scale, which is a self-reported measure of intensity ranging from 6 (no exertion) to 20 (maximal effort). Integrating heart rate data with RPE enables researchers to precisely customise exercise interventions to facilitate potential intervention outcomes whilst ensuring participant safety. Heart rate, ventilatory and metabolic data will be collected and measured by Medgraphics Ultima CPX breath by breath metabolic cart (MGC Diagnostics Corporation, USA).

Timepoint [6]

The initial baseline measure will be collected pre intervention on the first day of the assessment process and completion measure will be assessed on the final day of assessments with one week of the end of intervention process. (9 weeks post randomization).

Secondary outcome [7]

6-Minute Walk Test:
Functional capacity will be evaluated using the six-minute walk test. To reduce instances of freezing of gait that is associated in People with PD (PwP), participants will perform the walking test in an open outdoor space designed to minimise turning and associated freezing episodes. The goal is to cover as much ground as possible, by walking as fast as possible without running. Participants will be allowed to stop to rest, if necessary, but they will be asked to resume walking as soon as possible. Periods of stopping and freezing episodes will be recorded, as well as any other symptoms. Heart rate will also be collected at the beginning and the end of the test. Standard protocol includes verbal prompting to encourage maximal effort every 30 seconds as well as time checks every 2 minutes. The distance is recorded to the nearest cm using a rolling trundle wheel.

Timepoint [7]

The initial baseline measure will be collected pre intervention on the first day of the assessment process and completion measure will be assessed on the final day of assessments with one week of the end of intervention process. (9 weeks post randomization).

Secondary outcome [8]

Anaerobic capacity testing:
Participants randomised to the intervention will undertake a 60-second anaerobic capacity test on a combined arm and leg ergometer (Rogue Echo) to acquire workloads for the HIIT protocol. (85% average power attained over 60 seconds).

Timepoint [8]

The initial baseline measure will be collected pre intervention during the assessment process.
This test will be repeated at the end of the 4th week to allow for training adaptations and to allow for appropriate training intensities to be maintained.
Post intervention retesting will be assessed on the final day of assessments within one week of the end of intervention process. (9 weeks post randomization).

Secondary outcome [9]

Lower body one-repetition maximum (1RM) testing: (leg press)
Muscular strength assessment will be performed by a 1RM for the lower body using the leg press. Keiser A420 pneumatic resistance training equipment (Keiser Sports Health Equipment, Inc., Fresno, CA 93706, USA) will be used. Prior to attempting heavier loads, a warm-up of 2-4 repetitions with a light load will be performed followed by approximately 2 minutes rest. When lifts beyond an RPE of 15 are attempted, if successful, another lift will be attempted with a heavier load with approximately 1-minute rest between attempts. This will be continued until the participants are unable to complete a lift in good form to full unweighted range of motion twice (i.e., they must fail twice at the highest attempted load), with the 1RM being the heaviest load that was successfully lifted once with good form. The 1RM test will be repeated twice 1 week apart, with the higher of the two values recorded as the baseline 1RM.

Timepoint [9]

The initial baseline measure will be collected pre intervention on the second assessment day and a repeat test on the 3rd day of the assessment process with a completion measure assessed on the final day of assessments within one week of the end of intervention process. (9 weeks post randomization).

Secondary outcome [10]

Upper body one-repetition maximum (1RM) testing: (chest press).
Muscular strength assessment will be performed by a 1RM for the upper body using the chest press. Keiser A420 pneumatic resistance training equipment (Keiser Sports Health Equipment, Inc., Fresno, CA 93706, USA) will be used. Prior to attempting heavier loads, a warm-up of 2-4 repetitions with a light load will be performed followed by approximately 2 minutes rest. When lifts beyond an RPE of 15 are attempted, if successful, another lift will be attempted with a heavier load with approximately 1-minute rest between attempts. This will be continued until the participants are unable to complete a lift in good form to full unweighted range of motion twice (i.e., they must fail twice at the highest attempted load), with the 1RM being the heaviest load that was successfully lifted once with good form. The 1RM test will be repeated twice 1 week apart, with the higher of the two values recorded as the baseline 1RM.

Timepoint [10]

The initial baseline measure will be collected pre intervention on the second assessment day and a repeat test on the 3rd day of the assessment process with a completion measure assessed on the final day of assessments within one week of the end of intervention process. (9 weeks post randomization).

Secondary outcome [11]

Adherence to duration of intervention,
Attendance records will be kept for the number of intervention days attended by each participant.

Timepoint [11]

Each session (24 sessions).

Secondary outcome [12]

Adherence to intensity of intervention.
Participants workloads will be monitored throughout each interval and documented. Targets of 85% of average power obtained during the anaerobic capacity test will be implemented and average power over the total of 8 intervals (each session) calculated and tracked over the 24 sessions.

Timepoint [12]

Each interval (8 intervals per session) averaged over 24 sessions.

Secondary outcome [13]

Maximal gait speed.
For the maximal gait speed test, the participants will walk for four meters as fast as possible without breaking into a run, with a 2 metre acceleration/deceleration stage. The instructions will be “One-two-three-GO!” to prompt maximal effort. The same footwear will be required across all assessment timepoints. Equipment used will be a stopwatch, tape measure and witches hat cones.

Timepoint [13]

The initial baseline measure will be collected pre intervention on the first day of the assessment process and completion measure will be assessed on the final day of assessments with one week of the end of intervention process. (9 weeks post randomization)

Eligibility

Key inclusion criteria

Diagnosis of idiopathic PD with a severity of 3 or less on the Modified Hoehn and Yahr scale.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

Exclusionary criteria: A rating greater than 3 on the Modified Hoehn and Yahr scale or no physician diagnosis of PD. Non-community dwelling residential status. Currently participating in greater than 150 minutes of moderate- to high-intensity exercise training (defined as aerobic, resistance or high-intensity interval training) per week. Individuals with secondary PD or other progressive neurological disease. Unstable medical conditions that would preclude individuals from exercising. Known diagnosis of current or past coronary or cerebral artery disease, symptomatic peripheral vascular or other medical conditions precluding exercise: e.g., congestive heart failure, untreated aneurysms, cardiac arrythmias including atrial fibrillation, moderate-to-severe pulmonary disease, advanced renal disease or permanent non-ambulatory status, retinopathy or history of retinal detachment, a diagnosis of dementia or significant cognitive impairment as defined by a score less than 19 on the Montreal Cognitive Assessment (MoCA) indicating difficulties in aspects such as memory, communication, and ability to focus, medications that could indicate treatment of dementia, medications that could affect neurological function and safety including but not limited to anti-psychotics, sedatives-hypnotics or narcotic analgesics, as determined by the study physician assessment. Current musculoskeletal injuries, conditions, or limitations (e.g., muscle strain/pain and joint instability) of the lower body (i.e., ankle, knee, or hip joints), or current lower back pain. Symptoms consistent with current major depressive episode, suicidality, psychosis, or active substance use disorders, as defined by the Diagnostic and Statistical Manual, version 5R (DSM-5R). Recurrent falls. Non-ambulatory status (use of walker or stick allowed). Recurrent falls. Terminal or rapidly progressive illness.

Study design

Statistical methods / analysis

Descriptive statistics will be calculated for habitual gait speed, aerobic capacity, muscle strength/power, MDS-UPDRS score, functional performance (six-minute walk test and the SPPB), anerobic capacity and cognitive impairment before and after the intervention. The normality of the absolute data will be investigated using the Shapiro–Wilk test, and the Levene’s test will be used to assess the homogeneity of variance. For normally distributed data, means ± standard deviation (SD) and confidence interval (95% CI) will be reported. For non-normally distributed data median and interquartile ranges will be reported. Conditions will be analyzed using repeated measures mixed models for normally distributed data and an appropriate non-parametric test for non-normally distributed data if necessary. The primary analysis of interest is the group x time interaction from the mixed model. Covariates which will be added to the unadjusted model include age, sex, and baseline Modified Hoehn and Yahr rating. The primary analytic strategy will be intention-to-treat (ITT), with all randomised participants included in the models, regardless of adherence or availability of follow-up data. Secondary exploratory analyses will consider those with complete follow-up data (completers analyses) and those with high adherence (per protocol analyses). Statistical significance will be considered at the p<0.05 level. Mean differences, 95% CIs, and Hedges’ bias corrected Effect Sizes will be calculated for all outcomes

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/04/2024

Actual

Date of last participant enrolment

Anticipated

1/07/2025

Actual

Date of last data collection

Anticipated

1/10/2025

Actual

Sample size

Target

30

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Nil funding currently

Country [1]

Primary sponsor type

University

Name

University of Sydney

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Submitted, not yet approved

Ethics committee name [1]

University of Sydney Human research ethics committee

Ethics committee address [1]

University of Sydney, Camperdown campus, Camperdown, NSW

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

09/11/2023

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

An 8-week randomized feasibility trial will be conducted to investigate motor and non-motor responses to high-intensity interval training utilizing a combined arm and leg ergometer in individuals with mild to moderate Parkinson's disease (PD). 
control group will receive usual care.
Primary hypothesis 
High-intensity combined arm and leg ergometry added to usual care will lead to increases in habitual gait speed in people with PD compared to usual care.

Trial website

Public notes

Contacts

Principal investigator

Name

Dr Daniel Hackett

Address

University of Sydney, Susan Wakil Building D18 Camperdown, NSW.

Country

Australia

Phone

+61 424133724

Email

[email protected]

Contact person for public queries

Name

Philippe Jacquot

Address

University of Sydney, Susan Wakil Building D18 Camperdown, NSW.

Country

Australia

Phone

+61 414767925

Email

[email protected]

Contact person for scientific queries

Name

Philippe Jacquot

Address

University of Sydney, Susan Wakil Building D18 Camperdown, NSW.

Country

Australia

Phone

+61 414767925

Email

[email protected]

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
20877	Study protocol					386156-(Uploaded-27-11-2023-07-47-25)-Study-related document.docx
20878	Informed consent form					386156-(Uploaded-10-11-2023-12-28-51)-Study-related document.docx

Trial Review

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