Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000006842
Ethics application status
Approved
Date submitted
9/10/2020
Date registered
8/01/2021
Date last updated
8/01/2021
Date data sharing statement initially provided
8/01/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Investigating the differences in gut bacteria across ageing and in Parkinson's Disease
Scientific title
A Comparison of Gut Microbiome Profiles in Relation to Cognition and Neuroplasticity across Ageing and Parkinson’s disease
Secondary ID [1] 301091 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's disease 317161 0
Condition category
Condition code
Neurological 315307 315307 0 0
Parkinson's disease
Neurological 317804 317804 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The condition to be observed is Parkinson's disease, in comparison to healthy older adults who are age and sex-matched. Additionally, a group of healthy younger adults will be compared to the older adult group to determine age-related differences in a neurologically healthy population.

Physical activity monitors will be measured by actigraphy, sleep will be measured with a sleep diary and actigraphy, and diet will be assessed through the online ASA24-food recall questionnaire. Cognitive measures include the Montreal Cognitive Assessment (MoCA), National Adult Reading Test (NART), Trail making tests, the Cogstate brief battery, and three n-back tasks (1-, 2- and 3-back) whilst wearing a portable fNIRS (Brite 24 system) device by Artinis to measure the brains haemodynamic responses to the n-back tasks. Transcranial magnetic stimulation (TMS) measures of the Abductor Pollicis brevis and extensor carpi radialis muscles will be taken through a MagStim with BiStim attachment to allow for single-pulse measures of excitability (at 1.2 and 1.4x resting motor threshold) and for paired-pulse measures of inhibition (Short intracortical inhibition). These measures will occur before and after a complex finger-tapping task to determine any use-dependent neuroplasticity effects. Gut bacteria will be assessed through faecal samples collected by participants in their own home, before being sent back to Deakin University where they will be processed and then stored in -80 degrees freezers for later analysis (shotgun analysis). All measures are completely non-invasive.

The cognitive testing and TMS measures will take place prior to the other measures and will be conducted at Deakin University. Total duration for this on-campus session will be approximately 2 hours. All cognitive measures, excluding the MoCA and NART which are paper forms, will be completed on the computer. Specific instructions for the various tests will be communicated to participants on the day of testing. Following these, a screening form will be administered to ensure the participants eligibility to undergo TMS testing. If eligible TMS measures will be undertaken. Once complete, the physical activity monitors, faecal sample collection kit, written instructions, log-on information for the ASA24-diet recall and the sleep diary will be handed to participants along with a pre-paid mail envelope.

The total duration of the assessment sessions for the lifestyle measures of sleep and physical activity will be for 7 days, within this time frame 2 entries will be made to the ASA24-food recall. Faecal sample collection will only occur once within this time frame. There are no follow-up testing sessions or measures. Once complete the participant will return all study equipment and information, along with faecal sample, through the pre-paid envelop slip that was provided.
The measures and tests will be administered by a researcher (PhD candidate).
Intervention code [1] 317398 0
Not applicable
Comparator / control treatment
Control group will be age, and sex-matched healthy older adults (50-80years) free from any neurological condition and without any immediate family members diagnosed with Parkinson's disease. A younger adult group (18-35years) will act as a comparator/control group for the healthy older adult group.
Control group
Active

Outcomes
Primary outcome [1] 323562 0
Alpha-diversity differences of gut bacteria (from faecal sample) between groups, assessed through several alpha-diversity metrics including but not limited to Shannon's, Simpson's, Chao1, Observed Species etc.
Timepoint [1] 323562 0
Timepoint 0 (baseline assessment)
Primary outcome [2] 323563 0
Beta-diversity differences of gut bacteria (from faecal sample) between groups, assessed through several beta-diversity metrics including but not limited to weighted and unweighted UniFrac principle coordinate analysis, Bray-Curtis dissimilarity etc.
Timepoint [2] 323563 0
Timepoint 0 (Baseline Assessment)
Primary outcome [3] 323564 0
Absolute gut bacteria abundance differences between groups (assessed through shotgun metagenomic analysis of faecal samples)
Timepoint [3] 323564 0
Timepoint 0 (Baseline Assessment)
Secondary outcome [1] 382227 0
Sleep, assessed via a self-report sleep diary and actigraphy.
Timepoint [1] 382227 0
Timepoint 0 (Baseline)
Secondary outcome [2] 389252 0
Cognition.
Assessed via the Cogstate Brief battery for which a composite score will be calculated.
Timepoint [2] 389252 0
Timepoint 0 (Baseline).
Secondary outcome [3] 389253 0
Diet.
Measured through the average of 2 separate 24-hour recalls through the ASA-24.
Timepoint [3] 389253 0
Timepoint 0 (baseline)
Secondary outcome [4] 389254 0
Physical Activity assessed through actigraphy across a 7 day period.
Timepoint [4] 389254 0
Timepoint 0 (Baseline)
Secondary outcome [5] 389255 0
Brain haemodynamics.
Measured using fNIRS (Brite 24 system by Artinis) during 1-, 2- and 3-back cognitive tasks.
Timepoint [5] 389255 0
Timeline 0 (Baseline)
Secondary outcome [6] 389256 0
Neurophysiological measures. Transcranial magnetic stimulation will be used pre- and post-a motor training task to investigate neuroplasticity differences across groups.
Timepoint [6] 389256 0
Timepoint 0 (Baseline)

Eligibility
Key inclusion criteria
• 50-80 years for both groups (Healthy older and PD groups) and between 18-35 years for the healthy younger adult group
• Presence of PD, as determined through independent neurologist, for PD group. Level of severity (UPDRS stage II and III) will be determined and mild-moderate PD patients will be included. Note: No early onset PD cases to be included in the study, PD diagnosis has to have occurred at 50 years of age or later.
• For healthy older group, no neurological conditions present and no first-degree relatives with PD (determined through self-report questionnaires). No signs of Parkinsonism or symptoms associated with premotor PD (Assessed through the Unified Parkinson’s Disease Rating Scale (UPDRS stages II and III)
• greater than or equal to 24/30 for the healthy older group on the Montreal Cognitive Assessment (MoCA), greater than or equal to 21 for the PD group on the MoCA

For the healthy younger adult group:
• Aged between 18-35 years
• No neurological/neurodegenerative conditions and no first-degree relatives with PD (determined through self-report questionnaires)
• No signs of Parkinsonism or symptoms associated with premotor PD (Assessed through the Unified Parkinson’s Disease Rating Scale (UPDRS stages II and III)
• greater than or equal to 24/30 on the MoCA

Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Taken prebiotics (fibre supplementation, inulin etc.) or probiotics (Over the counter probiotics, , including Yakult or similar products) within previous 3 months
• Gastrointestinal diseases such as Colitis or Crohn’s disease
• Obesity (BMI greater or equal to 30)
• Drugs/Medication including proton-pump inhibitors and antibiotic use (within the previous 3 months)
• Current drug or alcohol abuse
• Conditions precluding TMS (epilepsy, pacemakers, metal implants etc.)
• PD individuals excluded if they have atypical or secondary Parkinsonism. Additional neurological conditions (i.e. stroke, epilepsy etc. will also be exclusions)
• Clinical diagnosis of depression, or a score of greater than 21 (21-30 indicates moderate depression) as assessed through Beck’s Depression Inventory

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Case control
Timing
Prospective
Statistical methods / analysis
Data will be collated and analysed through various software. Significance will be set at p < 0.05, unless otherwise specified (False Discovery Rate corrected for microbiome differential abundance analyses). Normality and homogeneity of the data will be assessed to determine if data is normally distributed. If data is not normally distributed transformations may be applied, or non-parametric tests utilised, depending on the results of the tests of normality.
Neuroplasticity measures (as determined through changes in the above TMS measures from pre- to post-motor task) will be compared between, and within, the two groups to examine any differences.
Diet (daily intake of nutrients and specific food groups) data obtained from the ASA24 online tool will be averaged across the two measurement days. From this, specific information of interest will be compared across the two groups. Data on sleep duration, as well as sleep efficiency, will be assessed between groups. The measure of physical activity will also be assessed between groups. These lifestyle factors will be compared between groups to determine if statistically significant differences exist.
Measures from the cognitive test battery will be assessed as a composite score of the four tasks to determine between group differences. If significant differences do exist between groups for the lifestyle factors, when assessing the cognitive data, covariates may be included in the regression model. If no significant differences between lifestyle factors exist, covariates will not be included.
Analysis of fNIRS data will involve taking data from the task period and analysing both O2Hb and HHb in relation to the individuals rest period (directly prior to task onset). This will allow for a comparison between groups as the data will be a relative change from rest to task. This information will be analysed to determine if significant differences in cognitive load differ between the groups.
After the generation of the DNA sequence reads bioinformatics analysis will be conducted on the data. This will involve assessing the presence and abundance of gut bacteria, calculating alpha- and beta-diversity, completing weighted and unweighted UniFrac measures and/or principle coordinate analysis (PCoA). Some measures of the gut bacteria may then be used to assess relationships between the gut microbiome and lifestyle factors, as well as with measures of cognition and neuroplasticity across the groups.
Depending on the between group differences for lifestyle factors, and/or various demographic (I.e. education level) data collected, this information may be used as covariates for the statistical tests utilised to assess between and/or within group differences.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
28/05/2019
Date of last participant enrolment
Anticipated
2/08/2021
Actual
Date of last data collection
Anticipated
31/08/2021
Actual
Sample size
Target
144
Accrual to date
53
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 30482 0
3125 - Burwood
Recruitment postcode(s) [2] 30483 0
3000 - Melbourne
Recruitment postcode(s) [3] 30484 0
3220 - Geelong
Recruitment postcode(s) [4] 30485 0
3216 - Waurn Ponds

Funding & Sponsors
Funding source category [1] 305526 0
University
Name [1] 305526 0
Deakin University
Country [1] 305526 0
Australia
Primary sponsor type
Individual
Name
Helen Macpherson
Address
Deakin University
221 Burwood Hwy, Burwood, VIC, 3125
Country
Australia
Secondary sponsor category [1] 305934 0
University
Name [1] 305934 0
Deakin University
Address [1] 305934 0
221 Burwood Hwy, Burwood, VIC, 3125
Country [1] 305934 0
Australia
Secondary sponsor category [2] 307927 0
Individual
Name [2] 307927 0
Nathan Nuzum
Address [2] 307927 0
Deakin University
221 Burwood Hwy, Burwood, VIC, 3125
Country [2] 307927 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305837 0
Deakin University Health Research Ethics Committee
Ethics committee address [1] 305837 0
Ethics committee country [1] 305837 0
Australia
Date submitted for ethics approval [1] 305837 0
03/12/2018
Approval date [1] 305837 0
30/01/2019
Ethics approval number [1] 305837 0
2018-386

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101770 0
Dr Helen Macpherson
Address 101770 0
Deakin University
221 Burwood Highway, Burwood, VIC, 3125
Country 101770 0
Australia
Phone 101770 0
+61 3 924 45317
Fax 101770 0
Email 101770 0
[email protected]
Contact person for public queries
Name 101771 0
Nathan Nuzum
Address 101771 0
Deakin University
221 Burwood Highway, Burwood, VIC, 3125
Country 101771 0
Australia
Phone 101771 0
+61 419 426 566
Fax 101771 0
Email 101771 0
[email protected]
Contact person for scientific queries
Name 101772 0
Nathan Nuzum
Address 101772 0
Deakin University
221 Burwood Highway, Burwood, VIC, 3125
Country 101772 0
Australia
Phone 101772 0
+61 419 426 566
Fax 101772 0
Email 101772 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
In our ethics application, and in Plain language statements to participants, we did not specify that individual participant data (IPD) would be shared. Therefore, we are opting to not share IPD.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.