research.tees.ac.uk file · Web viewMarguerite Harvey BSc,1 Kathryn L. Weston PhD,2 William K. Gray PhD,1 Ailish O’Callaghan MD,1,3 Lloyd L. Oates BSc,1 Richard Davidson MBBS1 and

High-intensity interval training in people with Parkinson’s disease: A

randomised, controlled feasibility trial

Marguerite Harvey BSc,1 Kathryn L. Weston PhD,2 William K. Gray PhD,1 Ailish

O’Callaghan MD,1,3 Lloyd L. Oates BSc,1 Richard Davidson MBBS1 and Richard

W. Walker MD1,4

1. Northumbria Healthcare NHS Foundation Trust, North Tyneside General

Hospital, Rake Lane, North Shields, Tyne and Wear, UK.

2. School of Health and Social Care, Teesside University, Middlesbrough,

UK

3. North Cumbria University Hospital NHS Trust, Cumberland Infirmary,

Carlisle, UK

4. Institute of Health and Society, Newcastle University, Newcastle-upon-

Tyne, UK

Correspondence to: Marguerite Harvey, Senior Specialist Physiotherapist,

Northumbria Healthcare NHS Foundation Trust, Jubilee Day Hospital, North

Tyneside General Hospital, Rake Lane, North Shields, NE29 8NH, UK;

telephone and fax: 0191 293 4344

[email protected]

Word count: Main text words 3382, abstract words 250, references 28, tables

4, figures 2, supplementary file 1.

Running Title: High-intensity interval training in Parkinson’s

Key Words: Parkinson’s disease, high-intensity Interval training, physiotherapy,

exercise

1

Declaration of sources of funding

This study was funded by a grant from The Graham Wylie Foundation, UK.

Speedflex Europe Ltd allowed use of their facilities and equipment free of

charge. Neither the Graham Wylie Foundation, Speedflex Europe Ltd nor any

employee of Speedflex Europe Ltd had any role in the design of the study, in

data collection or analysis, in the writing of this manuscript, or in the decision to

submit this manuscript for publication. Northumbria Healthcare NHS Foundation

Trust acknowledges the support of the National Institute of Health Research

Clinical Research Network (NIHR CRN).

Conflicts of interest statement

Dr Kathryn Weston was employed by Speedflex Europe Ltd as an exercise

physiologist from July 2013 to January 2014, but had no involvement with the

company at the time of the study.

Contributionship statement

This study was conceived, organised and managed by MH, RW, WKG, KW and

LO. Data collection was by MH, KW, WKG, RW and RD. Statistical analysis and

writing of the first draft of the paper was done by MH, KW, WKG. All listed

authors were involved in the preparation, review and critique of the final

manuscript.

2

ABSTRACT

Objectives: To investigate whether people with Parkinson’s disease can

exercise at high-intensity across a 12-week intervention and to assess the

impact of the intervention on cardiorespiratory fitness.

Design: A randomised, controlled, feasibility study with waiting list control.

Assessors were blinded to group allocation.

Setting: The intervention took place at an exercise center and assessments at

a district general hospital.

Subjects: Twenty people with idiopathic Parkinson’s disease.

Intervention: Thirty-six exercise sessions over 12 weeks, with each session

lasting ~45 minutes.

Main measures: Maximal heart rates achieved during exercise, recruitment

rate, attendance, drop-out, change in peak oxygen consumption, cardiac output,

cognitive function and quality of life. The study was considered technically

feasible if participants achieved ≥85% of maximal heart rate during exercise.

Results: There were 12 male and 8 female participants; they had a mean age

of 68.5 years (standard deviation 6.825). Two participants were of Hoehn and

Yahr stage I, 11 stage II and 7 stage III. Seventeen participants completed the

intervention. The median (interquartile range) proportion of repetitions delivered

across the intervention which met our high-intensity criterion was 80% (67% to

84%). Mean peak heart rate was 88.8% of maximal. Peak oxygen consumption

increased by 2.8 mL·kg-1·min-1 in the intervention group and 1.5 mL·kg-1·min-1 in

the control group after 12 weeks of exercise. We estimate that a fully powered

randomised controlled trial would require 30 participants per group.

3

Conclusions: High-intensity interval exercise is feasible in people with

Parkinson’s disease. Improvements in cardiorespiratory function are promising.

4

INTRODUCTION

In the past 10 years, evidence that exercise can be effective in improving

functional performance in people with Parkinson’s disease has grown steadily.1-3

However, there is little consensus on the most appropriate form, intensity or

duration of exercise.4

Traditionally, exercise programmes for people with Parkinson’s disease have

incorporated aerobic training and/or resistance training.5 Recently, the benefits

of more intense exercise have been investigated.2, 6 This includes the use of

high-intensity interval training; characterised by short, intermittent bursts of

vigorous exercise, interspersed with periods of recovery.7 However, in people

with Parkinson’s disease, engaging in any type of exercise can be complicated

by gait, balance, dyskinesia, co-ordination problems and autonomic dysfunction.

This can limit the choice of exercise modes and equipment. Therefore,

understanding whether people with Parkinson’s disease can perform high-

intensity interval training is of particular interest.

We aimed to: (1) Examine the extent to which people with Parkinson’s disease

can exercise at a high-intensity across a 12-week high-intensity interval training

intervention (2) Explore the intervention’s effect on clinical outcomes.

METHODS

This study ran from 18th January to 30th September 2016. It was conducted in

accordance with the Declaration of Helsinki, approved by the Newcastle and

North Tyneside Research Ethics Committee (reference number: 15/NE/0257) 5

and registered on the ISRCTN database (ISRCTN75458559). Informed consent

was obtained from each participant by a senior physiotherapist with a specialist

interest in Parkinson’s disease (MH) prior to enrolment. Northumbria

Healthcare NHS Foundation Trust was responsible for study integrity and

conduct and the study was funded by the Graham Wylie Foundation.

This was a technical (can people with Parkinson’s disease exercise at high

intensity) and operational (attendance rates, drop out, adverse events,

successful heart rate monitoring, assessments completed) feasibility study. It

used a randomised controlled design, with a waiting list control group. The

waiting list control group completed all post-intervention assessments.

Potential study participants were invited from the Northumbria Healthcare NHS

Foundation Trust Parkinson’s disease service. All patients known to the

services who had a diagnosis of idiopathic Parkinson’s disease according to the

UK Brain Bank Criteria,8 of Hoehn and Yahr stage I-III,9 had not participated in

an exercise study in the last 12 months, did not have a pacemaker or a history

of a serious cardiac event or of cardiac or cardiorespiratory dysfunction, had

sufficient cognitive ability to follow an exercise protocol (based on physician

assessment), and provided informed consent, were recruited to the study. The

Hoehn and Yahr staging system ranks Parkinson’s disease severity on a scale

from 1 (no/mild disability) to 5 (bed-bound). All participants underwent a

medical assessment by a doctor (RW, RD) prior to cardiopulmonary exercise

tests to assess their suitability for high-intensity interval training. Some of those

recruited were subsequently excluded on medical grounds (see Results).

6

Participants were randomised, using a random number generator by the study

statistician (WKG), to either an immediate start (intervention) or delayed start

(waiting list control) group. Stratification was used during randomisation to

allow an even distribution of ages and sex between the groups, with ages split

into ≤ 70 years and > 70 years. Group allocation was done after baseline

assessments to ensure blinding. At the second assessment point (after the

immediate start intervention group had completed their intervention) assessors

were blinded to group allocation and patients were reminded not to reveal their

allocation. Due to the nature of the intervention, none of the participants or

those supervising the high-intensity interval training sessions could be blinded.

Basic demographic data (age, sex) and disease characteristic (Hoehn and Yahr

stage9) and health status (body mass index, heart rate, blood pressure and

Barthel index10) data were collected on all participants. The Barthel Index

assessed a person’s functional status in basic activities of daily living on a scale

from 0 (severe disability) to 20 (no disability) and includes assessment of

feeding, washing, dressing, continence and mobility. Medication was reviewed

at baseline by a Parkinson’s disease nurse specialist and any changes made at

this point. No changes in medication regimes were made during the study

period.

Assessments were conducted at five timepoints, although not all participants

were assessed at all timepoints, depending on group allocation. At baseline

(before any intervention) and after the immediate start group had completed the

7

intervention all participants were assessed (weeks 13-14). After this, the

delayed start group completed the intervention and were assessed at this point

(week 27-28). In addition, all participants were assessed six-weeks after the

end of the intervention (week 18-19 for immediate start group and week 32-33

for delayed start group).

All assessments were conducted by research nurses, a senior physiotherapist

(MH) and a senior research associate (WKG). A doctor (RW, RD) was available

during all cardiopulmonary exercise tests to monitor cardiac response. Where

possible, tests for each participant were conducted at the same time of day to

comply with medication regimes.

Our primary feasibility outcomes were: the extent to which participants adhered

to our high-intensity exercise criterion of ≥85% of maximal heart rate (HRmax)

achieved during exercise, session attendance, drop out, adverse events, heart

rate recordings successful made and assessments completed. The following

clinical and functional assessments were conducted at all assessment

timepoints: cardiorespiratory function (see below), six-minute walk test (walking

in a clear corridor, turning (clockwise) every 30m around a cone), Montreal

Cognitive Assessment (MoCA)11 and 39-item Parkinson’s Disease

Questionnaire (Parkinson’s diseaseQ-39).12

Cardiorespiratory function was measured during cardiopulmonary exercise

testing of peak oxygen uptake (VO2peak) using a Quark Cardiopulmonary

Exercise testing system (COSMED Srl, Rome, Italy). Participants exercised on

8

a recumbent bicycle using a maximal ramp protocol. At the test onset

participants rested for three minutes on the bicycle. On instruction, they started

cycling with minimal resistance (25 watts) for three minutes, maintaining a

cadence of 55 to 65 revolutions per minute. The resistance was then gradually

increased by 5 watts, every 30 seconds, keeping the cadence at 55 to 65

revolutions per minute, until the patient reached exhaustion (test endpoint). The

study team provided prompts if cadence fell below 55 revolutions and verbal

encouragement as appropriate. Cardiac function was monitored throughout

using an electrocardiograph (ECG) and cardiac output was recorded using a

CHEETAH NICOMTM system (Cheetah Medical Inc., Boston, MA, USA). Key

data collected from the cardiopulmonary exercise testing were: 1) VO2peak

(mL·kg-1·min-1), defined as the highest VO2 obtained over a 30-s period during

the test; 2) HRmax, measured in beats·min-1 (bpm), defined as the highest heart

rate obtained during the cardiopulmonary exercise testing.

The immediate start intervention group exercised from February-May and the

delayed start group (waiting list control) from June-September 2016. Immediate

start participants began their 12-week intervention within seven days of

completing baseline testing. During this time, delayed start participants were

requested to maintain their usual lifestyle and physical activity habits, thus

acting as non-exercise controls. At the end of this period, and after all

participants were re-assessed, delayed start participants began their 12-week

intervention.

9

The senior physiotherapist (MH) and exercise scientist (KW) delivered 45 to 60

minute high-intensity interval training sessions in a private community exercise

facility thrice weekly. All participants were on anti-parkinsonian medication

throughout their 12-week intervention. Each high-intensity interval training

session took place at the same time of day (early afternoon) to comply with

medication regimes. In groups of up to five, participants completed an exercise

circuit designed to elicit a physiological response indicative of high-intensity

exercise (≥85% HRmax). Exercises were performed on double-concentric,

variable resistance Speedflex machines (Speedflex, AlphaTech Inc, Nelson,

NC) (Supplementary File 1). The Speedflex machine has a long arm lever,

which the participant holds onto. The motion of the arm responds to the amount

of force applied by the participant and stops moving when no force is applied.

As the resistance is set in both directions, the machine requires the participant

to apply force throughout an entire exercise. We elected to use the Speedflex

system following positive anecdotal feedback from patients who piloted the

system in the physiotherapy gym of our elderly medical day unit.

The high-intensity interval training sessions were based on a widely cited high-

intensity interval training protocol utilised in clinical populations.13 Each session

began with a 10-minute warm-up, which progressed in intensity and contained

whole-body movements (e.g. power clean and press, step and press, squat,

pulldown to squat, high pull and bent over row; see Supplementary File 1 for

exercise descriptions and images). Participants then completed four 4-minute

high-intensity exercise repetitions, each interspersed with 3.5 minutes recovery.

Repetitions consisted of a combination of four of the exercises described

previously, each performed for 45 s. After each 45-s exercise, participants

10

recovered for 15 s before beginning the next exercise. Participants received

strong verbal encouragement to work at a high-intensity during each repetition.

A 5-minute cool down completed each session. Over the 12-week intervention,

the number of repetitions per session increased by one every four weeks.

Throughout the high-intensity interval training sessions, heart rate was

monitored at 5-s intervals using the Polar Team2 system (Polar Electro,

Kempele, Finland) and participants were continually monitored for signs of

discomfort or distress by a research nurse. Following each session, we derived

the HRpeak for each high-intensity interval training repetition for each participant,

then expressed these as a percentage of the individual’s HRmax. At the

intervention onset, participants’ HRmax were determined as the highest 5-s value

recorded during the baseline cardiopulmonary exercise testing. If a participant

exceeded this value during the high-intensity interval training sessions, HRmax

was amended to the higher observed value.14

The minimum desirable sample size was established based on the likely key

clinical outcome for a future trial, change in VO2peak from baseline to post-

intervention. The minimum clinically important difference in VO2peak was

assumed to be 2 mL·kg-1·min-1, and the standard deviation no greater than 2.4.

Setting significance at 5% and power at 80% indicated a minimum sample size

of 14. Allowing for 20% drop-out rate and a 25% refusal rate in those

approached, required us to approach a minimum of 24 people and recruit 18.

11

Data were analysed using SPSS version 24 (IBM corporation, Armonk, NY).

HRpeak data (expressed as a percentage of HRmax) were analysed using

proportion analysis and linear mixed modelling.15 We determined the proportion

of repetitions in which the high-intensity exercise criterion (≥85% of HRmax) was

attained for each participant; then derived the median and interquartile range of

these individual proportions. As multiple exercise sessions repeated across an

intervention leads to between- and within-subject variability in the exercise

intensity response,15 we applied a linear mixed model to provide the between-

and within-subject variability (expressed as a standard deviation (SD)) in HRpeak

across the high-intensity interval training repetitions. These data are expressed

as mean ± SD, with uncertainty in the estimates expressed as 95% confidence

intervals (CI).

Both per-protocol and intention-to-treat analyses were undertaken for VO2peak

data. For intention-to-treat analysis the carry one forward approach was used,

with the median of all other participants used in the one case where no

assessments were conducted. Given the small sample size, non-parametric

descriptive statistics and inferential tests were used. For VO2peak data the mean

is quoted alongside the median. To compare clinical outcomes between the

immediate start and delayed start groups and from pre- to post-exercise,

standard non-parametric statistical tests were used (Wilcoxon signed-ranks test,

Mann-Whitney U test). Pearson’s correlation coefficient, calculated from the z-

score was used to estimate effect sizes, with cut offs of 0.1 (small effect size),

0.3 (medium) and 0.5 (large) used, as proposed by Cohen.16

12

RESULTS

Participant flow through the study is summarised in Figure 1 and key outcomes

in relation to feasibility are summarised in Table 1. Attendance rates were close

to 80% and only one minor adverse event was observed. Demographic

characteristics of the 20 participants at baseline are presented in Table 2.

Mean heart rates achieved during cardiopulmonary exercise testing and high-

intensity interval training are summarised in Table 1. All but one participant

attained their individual HRpeak from a high-intensity interval training session,

rather than the cardiopulmonary exercise testing. Missing heart rate data were

due to participants’ non-attendance rather than failure of the equipment, as

reflected by the similar proportion of sessions attended and percentage heart

rate data recorded. Participants’ mean HRpeak responses for each week of the

intervention are shown in Figure 2. In linear mixed modelling, with adjustment

for sex, age, disease stage and group allocation, there was an estimated

significant increase of 0.23% (95% CI 0.04 to 0.42, p = 0.019) per week in

mean HRpeak as a percentage of HRmax across the intervention period.

The waiting list control design also allowed us to compare the performance of

the two groups as if for a randomised controlled trial, since delayed start

participants initially acted as waiting list controls, these data are presented in

Table 3 for the VO2max data. Change in clinical and functional outcomes for

immediate and delayed start groups combined pre- to post-high-intensity

interval training and at 6-week follow up are presented in Table 4. There was a

significant improvement in VO2peak pre- to post-high-intensity interval training,

13

with a large effect size. This change was maintained at 6-weeks follow-up. A

future randomised controlled trial with α = 0.05, β = 0.2 and using the data from

Table 3 (combined standard deviation = 3.271), would require 30 participants

per group.

DISCUSSION

Our findings suggest that high-intensity interval training is feasible as an

exercise modality in people with Parkinson’s disease. All participants were able

to consistently exercise at high heart rate across the intervention period, drop-

out rates were relatively low and attendance rates high. We were able to collect

usable heart rate data for the vast majority of repetitions. No serious adverse

events were recorded. Across the whole cohort there was a significant

improvement in VO2peak from pre- to post-intervention and non-significant, but

medium effect size, improvement where the data were viewed as a randomised

controlled trial. No significant improvements in cardiac output, cognitive

function or quality of life were seen.

Interest in the use of high-intensity interval training for people with Parkinson’s

disease has increased in recent years.17-20 Yet comprehensive empirical data

demonstrating that people with Parkinson’s disease can exercise at a high-

intensity are lacking. We aimed to determine whether it was feasible for people

with Parkinson’s disease to exercise at high-intensity consistently. Analysis of

>2300 individual heart rate data points from 17 participants collected throughout

our intervention found the median proportion of exercise repetitions meeting our

high-intensity criterion was 80%. Further, as shown in Table 1, the high-

14

intensity stimulus was achieved across all participants (indicated by the small

between-subject standard deviation), throughout the intervention (indicated by a

small within-subject standard deviation). These data illustrate that participants

consistently reached our high-intensity criterion across their 12-week

programme. Collectively, these comprehensive findings support the use of

supervised high-intensity interval training in people with early- to mid-stage

Parkinson’s disease.

In clinical populations, a lack of data on whether individuals are capable of

exercising at high-intensity could have serious implications for adherence,

clinical outcomes and patient safety. Unfortunately, such omissions are

common across health intervention research, despite the introduction of

guidelines such as the Template of Intervention Description and Replication

(TIDieR) checklist.21 In our study, we have provided a full account of the high-

intensity interval training sessions, through detailed information on the exercises

conducted, the prescribed intensity of the sessions, and the actual intensity

achieved. This level of rigor in reporting and exercise training quantification

strengthens our conclusion that people with early stage Parkinson’s disease are

capable of consistently exercising at a high-intensity.

In line with previous exercise interventions in Parkinson’s disease,18 we

quantified exercise intensity relative to the highest heart rate achieved by each

individual during their cardiopulmonary exercise testing or high-intensity interval

training sessions. This approach is more appropriate than relying on generic

HRmax prediction equations, which do not take into consideration physiological

15

factors influencing heart rate such as gender, ethnicity, weight, fitness levels

and medication use.22 Further, in Parkinson’s disease autonomic dysfunction is

common which can also influence heart regulation.23 Failure to consider these

factors could result in a biased estimate of an individual’s ‘true’ HRmax, which

has implications for safety, physiological adaptations and the participant’s

exercise experience.

In absolute terms, our participants’ HRmax values are comparable to those

reported in other Parkinson’s disease exercise studies utilising incremental tests

to ascertain HRmax (range 132 to 152 bpm).19, 24, 25 Interestingly, in our study all

but one participant achieved their HRmax during a high-intensity interval training

session, supporting our decision to use the highest heart rate recorded across

the intervention for intensity quantification.14 However, this raises questions

over the suitability of a recumbent bicycle cardiopulmonary exercise testing

protocol to elicit maximal cardiovascular responses. Often, cycling protocols are

utilised in exercise studies in Parkinson’s disease due to gait and balance

problems.4 Although cycle ergometers may be preferred from a safety

perspective, it is widely acknowledged that it is more challenging to work

maximally when exercising only the lower limbs, as fatigue within the

quadriceps muscles often occurs prior to cardiovascular exhaustion.26 Although

the recent SPARX trial19 attempted to overcome this by using a treadmill-based

high-intensity interval training protocol, only patients that were drug naïve and of

Hoehn and Yahr stage I-II were recruited. This suggests that any motor

symptoms were very mild and, consequently, that safety issues commonly

associated with treadmill protocols may not have been an issue.

16

Although our study primarily explored feasibility, we also investigated the impact

of high-intensity interval training on clinical and functional outcomes that could

theoretically be altered if a high-intensity exercise stimulus was achieved.

These findings would help inform a future fully-powered trial. Here, we found a

significant improvement in VO2peak pre- to post-high-intensity interval training,

which was maintained at 6-week follow-up. Improvements in gait speed and

cognition were non-significant. When considering the data as that of a

randomised controlled trial, the between group differences, although non-

significant, showed a medium effect size. The recent SPARX study showed

improvements in VO2peak of similar magnitudes to ours, supporting the view that

our findings warrant further investigation through a fully powered trial.19

We acknowledge a number of limitations of our study. Our sample size was

relatively small compared to other high-intensity exercise in Parkinson’s disease

trials (e.g. SPARX19, thus limiting the conclusions able to drawn from the clinical

outcomes. Nevertheless, our primary focus was on feasibility, which could help

inform larger clinical trials. With regards to recruitment, we recognize that our

participants may not be fully representative of people with early- to mid-stage

Parkinson’s disease as only ~68% of those approached to take part consented.

Given the main reasons for non-participation were study length and

employment commitments, response rates could be improved by shortening the

overall intervention and/or conducting exercise sessions at evenings and

weekends. Since an ‘optimal’ dose of high-intensity interval training has yet to

be established for any health outcome in any population,27, 28 future work could

17

explore whether shorter interventions, delivered less frequently are favourable.

With regards to scalability, the Speedflex exercise system may not be

accessible to all Parkinson’s disease populations. Nonetheless, the exercises

were largely whole-body movements, which could be adapted and performed

using other types of equipment. Furthermore, we would caution against

extrapolation of our findings to people with more severe Parkinson’s disease.

In future work, comparison of high-intensity interval training with lower intensity

exercise would be of particular interest. Shulman et al2 reported low-intensity

and higher-intensity exercise regimes in people with Parkinson’s disease to

have similar impacts on cardio-respiratory fitness. However, the higher-intensity

exercise was only designed to elicit 70-80% of HRmax, and so may not fully

represent high-intensity exercise. In contrast, the SPARX study suggested

high-intensity exercise to be superior to moderate-intensity exercise, despite

participants achieving a lower percentage of HRmax (80.2%) during 30 minutes

of continuous exercise than seen in our study.19 As we have provided a fully

transparent and comprehensive overview of our 12-week high-intensity interval

training intervention, this should aid clinicians in their design, implementation

and evaluation of high-intensity interval training trials for people with

Parkinson’s disease. Future studies should also explore the wider impact of

high-intensity interval training on health, fitness and disease outcomes in

Parkinson’s disease populations, and continue to provide detailed intervention

protocol data. An economic analysis of the costs and benefits of such

interventions is also merited. Such information could start to enable questions

18

over the safest, most efficient and most effective way of exercising in people

with Parkinson’s disease to be answered.

Clinical messages

High-intensity interval training appears to be feasible and acceptable in

people with early to mid-stage Parkinson’s disease

Patient were able to consistently exercise at greater than 85% of their

maximal heart rate across the 12 week intervention

Significant improvements in cardiorespiratory fitness were seen across

the intervention period

19

Acknowledgements

We thank all people with Parkinson’s disease who participated in this study. We

would like to thank Steve Dodds, Moire McDonald, Hayley McKie, Kate Howorth

and all members of the Parkinson’s Team and the Research and Development

Department at Northumbria Healthcare NHS Foundation Trust who assisted in

data collection.

Competing interests and sources of funding

This study was funded by a grant from The Graham Wylie Foundation, UK.

Speedflex Europe Ltd allowed use of their facilities and equipment free of

charge. Neither the Graham Wylie Foundation, Speedflex Europe Ltd nor any

employee of Speedflex Europe Ltd had any role in the design of the study, in

data collection or analysis, in the writing of this manuscript, or in the decision to

submit this manuscript for publication. Northumbria Healthcare NHS Foundation

Trust acknowledges the support of the National Institute of Health Research

Clinical Research Network (NIHR CRN). Dr Kathryn Weston was employed by

Speedflex Europe Ltd as an exercise physiologist from July 2013 to January

2014, but had no involvement with the company at the time of the study.

Contributions

This study was conceived, organised and managed by MH, RW, WKG, KW and

LO. Data collection was by MH, KW, WKG, RW and RD. Statistical analysis and

writing of the first draft of the paper was done by MH, KW, WKG. All listed

authors were involved in the preparation, review and critique of the final

manuscript. RW acts as guarantor. 20

21

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26

Table 1: Key outcomes in relation to feasibility

Number recruited from those approached 22 from 32 approached (68.8%)

Started the intervention 20 (90.9%), 2 excluded on medical grounds

Completed the intervention 17 (85.0%)

Full set of assessment data collected on those completing the intervention

15 (88.2%)

Exercise sessions delivered 36

Exercise repetitions 180

Session attendance in those who completed the intervention

484 sessions attended on 612 possible (79.1%)

Adverse events One participant experienced a drop in blood pressure during a session, but was able to continue and did not report dizziness or light headedness

Heart rate data successfully recorded for those completing the intervention

2391 of a possible 3060 (78.1%)

Mean heart rate achieved during cardiopulmonary exercise testing (standard deviation)

121±13 beats per minute

Mean heart rate achieved during high-intensity interval training (standard deviation)

144±11 beats per minute

Mean HRpeak as a percentage of HRmax 88.8% (between-subject standard deviation 2.6% (95% CI 1.8 to 3.8); within-subject standard deviation of 5.0% (4.9 to 5.1)

Median percentage of repetitions where heart rate was ≥85% of HRmax

80.2% (interquartile range 67.1% to 83.8%)

HRmax = maximal heart rate achievable by an individualHRpeak = peak heart rate achieved by an individual during a given exercise session

27

Table 2: Demographic and clinical characteristics of patients at baseline assessment

Immediate start

(n = 10)

Delayed start

(n = 10)

Males 6 (60.0%) 6 (60.0%)

Mean age in years (standard deviation,

range) 68.0 (7.846, 55 to 79) 69.0 (6.018, 61 to 80)

Hoehn and Yahr stage

I 1 (10.0%) 1 (10.0%)

II 6 (60.0%) 5 (50.0%)

III 3 (30.0%) 4 (40.0%)

Mean heart rate beats per minute at rest

(standard deviation, range)

75 (4.57, 67 to 86) 72 (10.68, 68 to 77)

Mean body mass index (standard

deviation, range)

28.4 (4.569, 22.8 to

36.5)

26.4 (3.894, 22.8 to

36.5)

Mean systolic blood pressure at rest

(standard deviation, range)

133.2 (24.371, 101.0

to 176.0)

137.1 (21.294, 111.0

to 169.0)

Mean diastolic blood pressure at rest

(standard deviation, range)

80.2 (13.903, 59.0 to

100.0)

80.5 (12.430, 66.0 to

110.0)

Median Montreal cognitive assessment

score (IQR)

24.5 (21.8 to 25.3,

17.0 to 28.0)

25.5 (22.5 to 28.0,

21.0 to 30.0)

Median Barthel Index score (IQR) 18.5 (17.5 to 20.0,

15.0 to 20.0)

19.5 (18.0 to 20.0,

17.0 to 20.0)

IQR = inter-quartile range

28

Table 3. Outcome data following intervention for the immediate start group and control

condition for the delayed start group (13-14 weeks)

Intervention, n =

8

Control, n = 10 Significance

Median change in

VO2peak from

baseline (mL·kg-

1·min-1)

2.8, IQR 1.4 to

4.5 (mean 3.1,

SD 2.539)

1.5, IQR -3.0 to

3.8 (mean 0.7,

SD 3.555), 1

missing value

Per-protocol: U = 23.0, z = 1.251, p

= 0.236, r = 0.303 (medium effect

size), intention-to-treat: U = 29.0, z

= 1.587, p = 0.112, r = 0.355

(medium effect size)

Median change in

cardiac Index

(L/min/m2)

1.8, IQR -1.8 to

5.2

-0.2, IQR -2.8 to

6.5, 1 missing

value

U = 29.0, z = 0.674, p = 0.541, r =

0.163 (small effect size)

Median change in

six minute walk

test distance

(metres)

15.5, IQR -17.0

to 47.5

48.5, IQR -15.8

to 75.3

U = 32.5, z = 0.667, p = 0.515, r =

0.157 (small effect size)

Median change in

Montreal cognitive

assessment total

3.0, IQR 0.5 to

4.0

2.0, IQR -0.5 to

3.3

U = 30.5, z = 0.857, p = 0.408, r =

0.202 (small effect size)

Median change in

Parkinson’s

disease-39 total

score

1.0, IQR -8.3 to

15.3

-0.5, IQR -5.2 to

5.8

U = 35.0, z = 0.445, p = 0.696, r =

0.164 (small effect size)

SD = standard deviation, IQR = inter-quartile range

29

Table 4: Combined outcome data for all participants pre- and post-intervention

Pre-high-

intensity

interval

training, n 16

Post-high-

intensity

interval

training, n = 16

6-week follow-

up, n = 16

Significance of

change from

pre-high-

intensity

interval

training to

post-high-

intensity

interval

training

Median VO2peak

(mL/min/kg)

20.6 (IQR 19.9

to 26.0), 1

missing value

21.8 (IQR 18.9

to 29.1), 1

missing value

22.7 (IQR 19.2

to 29.6), 1

missing value

Per-protocol: z =

2.045, p =

0.041, r = 0.528

Intention-to-

treat: z = 2.277,

p = 0.023, r =

0.509

Mean VO2peak

(mL/min/kg)

21.9, SD 3.920,

1 missing value

24.0, SD 5.351,

1 missing value

25.5, SD 8.447,

1 missing value

Per-protocol: t =

2.356, p =

0.034, r = 0.532

Intention-to-

treat: t = 2.362,

p = 0.029, r =

0.534

IQR = inter-quartile range, SD = standard deviation, VO2peak (mL/min/kg) = peak oxygen

consumption measured in millilitres per minute per kilogram of body weight

1

Figure 1: CONSORT participant flowchart

1

Invited to participate (n=32)Excluded on medical grounds (n=2)Reason (n): Angina (1), blood pressure response to exercise (1)

Declined to participate (n=10)Reason (n): Work commitments (2), pre-booked vacations (2), length of study too long (6)

Included in clinical outcomes analysis (n=8)

Allocated to immediate start group (n=10) Allocated to delayed start group (n=10)

Included in clinical outcomes analysis as randomised controlled trial (n=9)Included in clinical outcomes analysis as pre- post-intervention study (n=7)Excluded from analysis (n=1)Reason (n): Failure to comply with the cardiopulmonary exercise test protocol due to severe tremor.

Allocation

Analysis

Randomized (n=20)

Enrollment

Assessments

Post intervention assessment (n=8)Not assessed (n=2)Reasons (n): discontinued assessment due to Ill health (1), discontinued assessment due to partner’s ill health (1)

Week 0

Week 13-14

Week 18-19

Baseline assessment (n = 10) Baseline assessment (n = 10)

Post-intervention assessment (n = 8)Not assessed (n = 2)Reasons (n): discontinued intervention due to Ill health (1), did not attend assessment due to ill-health (1)

Re-assessment at end of control period (n = 10)

6 weeks post-intervention assessment (n = 9)

Week 27-28

6 weeks post-intervention assessment (n = 9)Week

32-33

2

Figure 2: Mean (large closed diamonds) and individual participants’ (small

closed circles) heart rate responses for each week of the high-intensity

interval training intervention

3