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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
Date results information 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] 288848 0
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 298136 0
Parkinson's disease dementia 298139 0
Condition category
Condition code
Physical Medicine / Rehabilitation 298303 298303 0 0
Other physical medicine / rehabilitation
Neurological 298304 298304 0 0
Dementias
Neurological 298305 298305 0 0
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] 294306 0
Treatment: Other
Intervention code [2] 294307 0
Lifestyle
Intervention code [3] 294338 0
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] 297781 0
Functional independence of participant:
- Change in Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) subsection and total score
Timepoint [1] 297781 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [1] 322210 0
Functional status:
- ALSAR (IADLs)
Timepoint [1] 322210 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [2] 322211 0
Functional status:
- ALSAR (IADLs)
Timepoint [2] 322211 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [3] 322212 0
Functional independence of participant:
- Functional Independence Measures (FIM)
Timepoint [3] 322212 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [4] 322213 0
Participant QoL:
- DEMQoL (QoL)
Timepoint [4] 322213 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [5] 322214 0
Participant Negative Affect:
- GDS - 15 item (Depression)
Timepoint [5] 322214 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [6] 322215 0
Participant life satisfaction:
- Satisfaction with life scale (SWLS)
Timepoint [6] 322215 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [7] 322216 0
Nutritional status:
Mini Nutritional assessment (MNA)
Timepoint [7] 322216 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [8] 322217 0
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] 322217 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [9] 322218 0
Anthropometry:
- change in fat % via BIA measurement
Timepoint [9] 322218 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [10] 322220 0
Anthropometry:
Body mass index (using height and weight measurements)
Timepoint [10] 322220 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover) *Height will only be taken at Baseline.
Secondary outcome [11] 322221 0
Blood pressure:
- Orthostatic Blood pressure

Timepoint [11] 322221 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [12] 322222 0
Caregiver QoL:
- QOLS (QoL)
Timepoint [12] 322222 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [13] 322332 0
Caregiver Burden:
- ZARIT 12 item (Burden)
Timepoint [13] 322332 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [14] 322333 0
Caregiver life satisfaction:
- SWLS
Timepoint [14] 322333 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [15] 322334 0
Caregiver affect:
- PANAS (positive/negative affect)
Timepoint [15] 322334 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [16] 322335 0
Caregiver perception/rating of Participant behaviour:
- NPI
Timepoint [16] 322335 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [17] 322336 0
Life space assessment:
Life space assessment tool [LSA]
Timepoint [17] 322336 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [18] 322337 0
Anthropometry:
Waist circumference (using tape measure and ISAK measurement method)
Timepoint [18] 322337 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [19] 322338 0
Participant Activity levels / sedentary time / Gait variability:
- AX3 axivity monitoring of participants for 1 week
Timepoint [19] 322338 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [20] 322608 0
Cognition:
PD-CRS (global cognition)
Timepoint [20] 322608 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [21] 322609 0
Cognition:
Trail making (Executive function)
Timepoint [21] 322609 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [22] 322610 0
Physical function:
- Short Physical performance battery (SPPB)
Timepoint [22] 322610 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [23] 322611 0
Physical function:
- Tandem walk
Timepoint [23] 322611 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [24] 322612 0
Physical function:
- 6MWT
Timepoint [24] 322612 0
Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [25] 322613 0
Physical function:
- Grip strength
Timepoint [25] 322613 0
Baseline, 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [26] 322617 0
Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - leg press
Timepoint [26] 322617 0
Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [27] 322618 0
Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - leg extension
Timepoint [27] 322618 0
Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [28] 322619 0
Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - leg flexion
Timepoint [28] 322619 0
Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [29] 322620 0
Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - hip abduction
Timepoint [29] 322620 0
Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [30] 322621 0
Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - hip extension
Timepoint [30] 322621 0
Baseline (during third assessment session, which is a visit to Lidcombe campus, 0wk), 8 week (pre-crossover), 16 weeks (post-crossover)
Secondary outcome [31] 322622 0
Strength testing:
Keiser Pneumatic testing of 1RM Isotonic strength and power - triceps extension.
Timepoint [31] 322622 0
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
Gender
Both males and females
Can healthy volunteers participate?
No
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
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 293206 0
University
Name [1] 293206 0
University of Sydney
Address [1] 293206 0
Exercise, Health, and Performance Faculty Research Group
75 East Street, Lidcombe, NSW, Australia, 2141
Faculty of Health Sciences, University of Sydney
Country [1] 293206 0
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] 292008 0
None
Name [1] 292008 0
Address [1] 292008 0
Country [1] 292008 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294690 0
University of Sydney HREC 2
Ethics committee address [1] 294690 0
Human Ethics Office
Margaret Telfer Building (K07)
University of Sydney
NSW 2006
Ethics committee country [1] 294690 0
Australia
Date submitted for ethics approval [1] 294690 0
25/02/2016
Approval date [1] 294690 0
20/04/2016
Ethics approval number [1] 294690 0
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 64678 0
Prof Maria Fiatarone Singh
Address 64678 0
University of Sydney
K221, Cumberland Campus
75 East Street, Lidcombe, 2141
NSW, Australia
Country 64678 0
Australia
Phone 64678 0
+612 9351 9755
Fax 64678 0
Email 64678 0
maria.fiataronesingh@sydney.edu.au
Contact person for public queries
Name 64679 0
Mr Michael Inskip
Address 64679 0
University of Sydney
K220, Cumberland Campus
75 East Street, Lidcombe, 2141
NSW, Australia
Country 64679 0
Australia
Phone 64679 0
+61 2 9351 9138
Fax 64679 0
Email 64679 0
michael.inskip@sydney.edu.au
Contact person for scientific queries
Name 64680 0
Prof Maria Fiatarone Singh
Address 64680 0
University of Sydney
K221, Cumberland Campus
75 East Street, Lidcombe, 2141
NSW, Australia
Country 64680 0
Australia
Phone 64680 0
+612 9351 9755
Fax 64680 0
Email 64680 0
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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary