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Trial registered on ANZCTR

Registration number

ACTRN12616000466448

Ethics application status

Approved

Date submitted

29/03/2016

Date registered

8/04/2016

Date last updated

12/12/2018

Date data sharing statement initially provided

12/12/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

Promoting Independence in Lewy Body Dementia through Exercise

Scientific title

The PRIDE trial: Promoting Independence in Lewy Body Dementia through Exercise

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

The PRIDE trial

Linked study record

Health condition

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

Lewy body dementia

Parkinson's disease dementia

Condition category

Condition code

Physical Medicine / Rehabilitation

Other physical medicine / rehabilitation

Neurological

Dementias

Neurological

Parkinson's disease

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Summary:
The pride trial involves two sections; a cross-sectional baseline study taking place at the place of residence of the participant with LBD, and a 16-week fixed period controlled crossover trial consisting of 8-weeks usual care (baseline control) followed by 8-weeks exercise intervention.

The cross-sectional baseline study will evaluate covariates of functional independence (via the MDS-UPDRS measure) in a cohort of community dwelling and assisted living participant with LBD and aims to identify correlates that are potentially amenable with a targeted exercise intervention. Correlates that will be analysed include assessments of IADLs (ALSAR), ADLs (Bayer-informant), Other measures of functional independence (FIM), demographics (including pet care), body composition (BIA, weight, height, Waist circumference), Orthostatic blood pressure, static (SPPB) and dynamic balance (Tandem walk), gait stability (Axivity, AX3 monitors), gait speed (habitual and fast), walking endurance (6MWT, Step on spot test, 6MWT), physical activity levels and sedentary behaviour (Axivity, AX3 monitors), cognition (PD-CRS, Trail making, reaction time) and visual processing (Hooper Visual integration test, BVRT), upper and lower limb strength and power (Dynamometer assessment of major muscle groups, sit-to-stand test, grip strength), disease status (Clinical dementia rating), medication use, home environment assessment, nutritional assessment (Mini Nutritional assessment) and falls history. Participant Affect, Life-space and Quality of Life (DEM-QOL, GDS, SWLS, LSA) as well as caregiver affect, burden and Quality of life (PANAS, QOLS, NPI, ZARIT-12item) will also be assessed. A subset of these measures will form the primary and secondary outcomes evaluated in the 16-week fixed period controlled crossover trial (detailed in outcomes section).

A community dwelling subset of individuals will then be offered the opportunity to take place in the 16-week fixed period controlled crossover trial involving exercise intervention to evaluate the effects of a targeted exercise intervention on functional independence (MDS-UPDRS) in participants living with LBD.

The exercise intervention will involve cueing, strength, balance, dual-tasking and mindfulness components delivered in the clinic at the Cumberland Campus of the University of Sydney (Lidcombe, NSW) by trained exercise professionals in one hour sessions, 3 sessions/week for 8-weeks This will be supplemented by strategies tailored to each participant to increase incidental physical activity outside of the training sessions.

Intervention specific details:
- Mode of Delivery: Face-to-face sessions delivered in small groups of participants with the assistance of caregivers
- Location of intervention: The Intervention will take place at the Cumberland campus of the University of Sydney in Lidcombe, NSW, Australia. The home baseline cross-sectional assessments will take place at the Individual's place of residence, while all follow up assessments will take place at the Lidcombe campus.
- Materials / equipment used: The Exercise prescription consisting of cueing, balance, strength, dual-tasking and mindfulness components will use Keiser pneumatic strength machines, a clinical treadmill, audio and visual cueing devices such as metronomes, verbal feedback and visual instructions. Additional assessment equipment include ultra-timer gait devices, and dynamometers for measurement of static strength.
- Types of activities: Those activities listed previously will be adjusted to each individual depending on ability and need based upon the individual and cohort results from assessment and current best practice in Parkinson's disease populations. This approach is a 3-tiered approach as described below:
+Tier 1 prescription (modality, duration, etc.) is informed from a literature review of current best practice in Parkinson’s disease as well as dementia populations. No statistical analysis will be performed in this tier. This will occur prior to the PRIDE exercise intervention commencing.
+Tier 2 will be informed from evaluation of linear regression models for each of the co-variables in the baseline cross-sectional study. Those variables with highest correlation with functional independence measures and that are potentially amenable to exercise will provide a priority for the order and focus on modalities used in the intervention. This process will be an ongoing process informed by the gradual addition of data from participants entering the cross-sectional baseline assessment.
+Tier 3 will be fine adjustments for each individual based on medical history, functional capacity and cognitive ability. No statistical analysis will be performed in this tier. This process will be finalised after Baseline assessment and review by Study physician Prof. Fiatarone Singh.

The resultant program will resemble a combination of interventions reported in Parkinson's disease with priority in order given to those that best target the mediating factors identified in the Baseline cross-sectional study. Each program will then be modified to best elicit exercise gains in the individual taking into consideration their current ability and limitations.

Physical activity adoption strategies: This process will be dependent on the results of the cross-sectional baseline study. The levels of physical activity and sedentary times will be analysed during the usual care control period and compared to similar cohorts in Parkinson's disease and healthy age-matched control cohorts. Targets will be set as part of the exercise prescription to increase incidental physical activity using small, but incremental increases in daily PA (i.e. integrating walks into the daily routine, intervening long sedentary periods with shorts periods of standing, etc).

Adherence and Fidelity:
This will be measured through percentage completion of full protocol sessions. We will record attendance at these sessions as well as specific components of adherence including number of exercises performed, amount of weight lifted, difficulty levels of balance exercises, heart rate during aerobic activities and perceived exertion during aerobic and strengthening exercises. We will also record any other open ended feedback on their perceptions of enjoyment or discomfort, etc.

Adverse events:
We will capture all adverse events during the intervention and assessment periods. This will be achieved by weekly questionnaire/interview including proxy information obtained whenever necessary to minimize missing data. Adverse events will include any exacerbation of underlying disease, or new onset musculoskeletal, cardiovascular, or metabolic abnormality attributed directly to study protocols. Specific adverse events that will be routinely monitored include: falls, cardiac events during physical testing and exercise training (angina, arrhythmias, blood pressure excursions, clinically significant ECG changes); fatigue and muscle soreness or musculoskeletal injury following training; In addition, subjects will be asked to report all changes in medication, health care professional visits, new diagnoses, acute illnesses, or any new symptoms.

Intervention code [1]

Treatment: Other

Intervention code [2]

Lifestyle

Intervention code [3]

Rehabilitation

Comparator / control treatment

Baseline control group - non-randomized controlled crossover trial.

Each participant will undergo 8 weeks of usual care prior to starting the exercise intervention. Usual care will be defined as the normal level of medical care provided for the individual since diagnosis inclusive of medical, physical therapy and pharmaceutical treatments.

Control group

Active

Outcomes

Primary outcome [1]

Functional independence of participant:
- Change in Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) subsection and total score

Timepoint [1]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [1]

Functional status:
- ALSAR (IADLs)

Timepoint [1]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [2]

Functional status:
- ALSAR (IADLs)

Timepoint [2]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [3]

Functional independence of participant:
- Functional Independence Measures (FIM)

Timepoint [3]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [4]

Participant QoL:
- DEMQoL (QoL)

Timepoint [4]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [5]

Participant Negative Affect:
- GDS - 15 item (Depression)

Timepoint [5]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [6]

Participant life satisfaction:
- Satisfaction with life scale (SWLS)

Timepoint [6]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [7]

Nutritional status:
Mini Nutritional assessment (MNA)

Timepoint [7]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [8]

Habitual Gait speed - assessed with ultra-timer laser gait device measurement. Average of two trials within 0.02 s of each other used.

Timepoint [8]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [9]

Anthropometry:
- change in fat % via BIA measurement

Timepoint [9]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [10]

Anthropometry:
Body mass index (using height and weight measurements)

Timepoint [10]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover) *Height will only be taken at Baseline.

Secondary outcome [11]

Blood pressure:
- Orthostatic Blood pressure

Timepoint [11]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [12]

Caregiver QoL:
- QOLS (QoL)

Timepoint [12]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [13]

Caregiver Burden:
- ZARIT 12 item (Burden)

Timepoint [13]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [14]

Caregiver life satisfaction:
- SWLS

Timepoint [14]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [15]

Caregiver affect:
- PANAS (positive/negative affect)

Timepoint [15]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [16]

Caregiver perception/rating of Participant behaviour:
- NPI

Timepoint [16]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [17]

Life space assessment:
Life space assessment tool [LSA]

Timepoint [17]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [18]

Anthropometry:
Waist circumference (using tape measure and ISAK measurement method)

Timepoint [18]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [19]

Participant Activity levels / sedentary time / Gait variability:
- AX3 axivity monitoring of participants for 1 week

Timepoint [19]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [20]

Cognition:
PD-CRS (global cognition)

Timepoint [20]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [21]

Cognition:
Trail making (Executive function)

Timepoint [21]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [22]

Physical function:
- Short Physical performance battery (SPPB)

Timepoint [22]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [23]

Physical function:
- Tandem walk

Timepoint [23]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [24]

Physical function:
- 6MWT

Timepoint [24]

Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [25]

Physical function:
- Grip strength

Timepoint [25]

Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [26]

Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - leg press

Timepoint [26]

Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [27]

Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - leg extension

Timepoint [27]

Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [28]

Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - leg flexion

Timepoint [28]

Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [29]

Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - hip abduction

Timepoint [29]

Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [30]

Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - hip extension

Timepoint [30]

Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)

Secondary outcome [31]

Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - triceps extension.

Timepoint [31]

Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)

Eligibility

Key inclusion criteria

Diagnosis of mild LBD (15>MMSE<24), over the age of 55, ambulatory, able to follow rudimentary instructions, able to tolerate functional testing, able to travel to gym facility (with caregiver) and complete 3 sessions/week for 8 weeks of exercise.

Minimum age

55 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Non-English speaking or non-verbal, moderate to severe dementia, wheelchair, chair- or bed-bound, presence of major limiting musculoskeletal, cardiovascular or other neurological condition precluding planned testing and training.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Crossover

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

The required powering of the PRIDE trial is modelled off studies investigating exercise in Parkinson's disease populations employing the MDS-UPDRS as a main outcome measure. To be able to show moderate correlations (r=0.5) with beta=0.20 and alpha=0.05 for the baseline cross-sectional mediation analysis, we calculate a minimum of 30 participants are needed factoring in an expected attrition rate of 15-20% (Norwalk et al. 2001, Moore et al, 2013). The power calculations for the fixed period crossover trial require a minimum of 24 participants to demonstrate significance for an effect size of 0.61 (with Beta=0.20 and alpha=0.05). These calculations are based upon results described in a cohort of individuals with moderate to severe PD trained for 8 weeks with the same primary functional independence outcome measure (MDS-UPDRS) (Rose et al. 2013).

- Data collected from the cross-sectional baseline study will be evaluated through mediation analysis to determine the casual relationship between tested variables (such as strength, affect, sedentary time), and determine the causal effects of select variables on the primary outcomes of functional independence (MDS-UPDRS, FIM, Gait speed). For instance, low knee extensor strength might be found to correlate with high levels of sedentary behaviour, which in turn will impact on the functional independence of an individual.
The above mediation analysis will be performed prior to the start of the exercise intervention.

- The exercise intervention will be informed from evaluation of linear regression models for each of the co-variables in the baseline cross-sectional study. Those variables will highest correlation with functional independence measures and are potentially amenable to exercise will provide a priority for the order and focus on modalities used in the intervention

- The efficacy of the fixed period crossover trial will be measured with a repeated measures analysis of variance on all variables collected during each time point (0wk, 8wk, 16wk), including measures of caregiver stress, burden and QoL.

Recruitment

Recruitment status

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Lack of funding/staff/facilities
Participant recruitment difficulties

Date of first participant enrolment

Anticipated

2/05/2016

Actual

9/08/2016

Date of last participant enrolment

Anticipated

1/01/2018

Actual

27/12/2017

Date of last data collection

Anticipated

Actual

30/03/2018

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Sydney

Address [1]

Exercise, Health, and Performance Faculty Research Group
75 East Street, Lidcombe, NSW, Australia, 2141
Faculty of Health Sciences, University of Sydney

Country [1]

Australia

Primary sponsor type

University

Name

The University of Sydney

Address

Exercise, Health, and Performance Faculty Research Group
75 East Street, Lidcombe, NSW, Australia, 2141
Faculty of Health Sciences, University of Sydney

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Sydney HREC 2

Ethics committee address [1]

Human Ethics Office
Margaret Telfer Building (K07)
University of Sydney
NSW 2006

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

25/02/2016

Approval date [1]

20/04/2016

Ethics approval number [1]

2016/209

Summary

Brief summary

LBD is an aggressive disease with a prevalence of up to 30.5% of all diagnosed dementia cases. Diagnosed individuals not only display symptoms of dementia such as memory loss, dysfunction in problem solving and decision making, but also display symptoms of Parkinsonism such as slow movement (bradykinesia), resting tremor, and freezing of gait while walking. In addition, Individuals with LBD also experience psychotic symptoms such as visual and auditory hallucinations and delusions, as well as autonomic symptoms such as incontinence, orthostatic hypotension (low blood pressure upon standing), and disrupted sleep patterns. The culmination of this cluster of symptoms is a significant reduction in functional independence and a subsequent increase in reliance on caregivers, increasing stress and burden in both individuals. 

Exercise research is scarce in this population, with very limited and low quality data available. In similar cohorts though, Like Parkinson's disease and other types of dementia, exercise of a variety of modalities has shown efficacy in improving physical function among other variables. Further to this, increasing incidental physical activity around the home has also been reported to improve function in individuals with Parkinson's disease. Logically, exercise could show similar benefits in Lewy Body dementia cohorts.

The PRIDE trial will be a world first trial investigating the magnitude of the risk factors that contribute most to a loss in functional independence in individual with LBD, and then using that information in combination with evidence based best practice to design an 8-week exercise intervention to be trailed in community dwelling participants with LBD.

PRIDE will include a cross-sectional baseline study of LBD, followed by a  16-week, fixed-period crossover controlled trial of targeted exercise. Participants will be tested at baseline in a cross-sectional analysis of the most important modifiable factors in LBD mediating functional independence.

 A subset of the recruited cohort who lives in the community will then be enrolled in an 8- wk usual care control period followed by an 8-wk experimental exercise intervention. Randomisation is not possible due to carry- over effects of exercise. All outcomes will be measured at three timepoint: at baseline just before wait-list control period, after 8 weeks of wait-list control, and after 8 weeks of exercise intervention (Week 16) by the same assessor to minimise issues related to inter-rater reliability.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Maria Fiatarone Singh

Address

University of Sydney
K221, Cumberland Campus
75 East Street, Lidcombe, 2141
NSW, Australia

Country

Australia

Phone

+612 9351 9755

Fax

maria.fiataronesingh@sydney.edu.au

Contact person for public queries

Name

Michael Inskip

Address

University of Sydney
K220, Cumberland Campus
75 East Street, Lidcombe, 2141
NSW, Australia

Country

Australia

Phone

+61 2 9351 9138

Fax

michael.inskip@sydney.edu.au

Contact person for scientific queries

Name

Maria Fiatarone Singh

Address

University of Sydney
K221, Cumberland Campus
75 East Street, Lidcombe, 2141
NSW, Australia

Country

Australia

Phone

+612 9351 9755

Fax

maria.fiataronesingh@sydney.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Undecided

No/undecided IPD sharing reason/comment

Still discussing among investigators

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

Source	Title	Year of Publication	DOI
Embase	Promoting independence in Lewy body dementia through exercise (PRIDE) study: Protocol for a pilot study.	2019	https://dx.doi.org/10.1016/j.conctc.2019.100466
Embase	Promoting independence in Lewy body dementia through exercise: the PRIDE study.	2022	https://dx.doi.org/10.1186/s12877-022-03347-2

N.B. These documents automatically identified may not have been verified by the study sponsor.

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