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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]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Parkinson's disease

Condition category

Condition code

Neurological

Parkinson's disease

Neurological

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]

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]

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]

Timepoint 0 (baseline assessment)

Primary outcome [2]

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]

Timepoint 0 (Baseline Assessment)

Primary outcome [3]

Absolute gut bacteria abundance differences between groups (assessed through shotgun metagenomic analysis of faecal samples)

Timepoint [3]

Timepoint 0 (Baseline Assessment)

Secondary outcome [1]

Sleep, assessed via a self-report sleep diary and actigraphy.

Timepoint [1]

Timepoint 0 (Baseline)

Secondary outcome [2]

Cognition.
Assessed via the Cogstate Brief battery for which a composite score will be calculated.

Timepoint [2]

Timepoint 0 (Baseline).

Secondary outcome [3]

Diet.
Measured through the average of 2 separate 24-hour recalls through the ASA-24.

Timepoint [3]

Timepoint 0 (baseline)

Secondary outcome [4]

Physical Activity assessed through actigraphy across a 7 day period.

Timepoint [4]

Timepoint 0 (Baseline)

Secondary outcome [5]

Brain haemodynamics.
Measured using fNIRS (Brite 24 system by Artinis) during 1-, 2- and 3-back cognitive tasks.

Timepoint [5]

Timeline 0 (Baseline)

Secondary outcome [6]

Neurophysiological measures. Transcranial magnetic stimulation will be used pre- and post-a motor training task to investigate neuroplasticity differences across groups.

Timepoint [6]

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

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment postcode(s) [1]

3125 - Burwood

Recruitment postcode(s) [2]

3000 - Melbourne

Recruitment postcode(s) [3]

3220 - Geelong

Recruitment postcode(s) [4]

3216 - Waurn Ponds

Funding & Sponsors

Funding source category [1]

University

Name [1]

Deakin University

Address [1]

221 Burwood Hwy, Burwood, VIC, 3125

Country [1]

Australia

Primary sponsor type

Individual

Name

Helen Macpherson

Address

Deakin University
221 Burwood Hwy, Burwood, VIC, 3125

Country

Australia

Secondary sponsor category [1]

University

Name [1]

Deakin University

Address [1]

221 Burwood Hwy, Burwood, VIC, 3125

Country [1]

Australia

Secondary sponsor category [2]

Individual

Name [2]

Nathan Nuzum

Address [2]

Deakin University
221 Burwood Hwy, Burwood, VIC, 3125

Country [2]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Deakin University Health Research Ethics Committee

Ethics committee address [1]

Deakin Research Integrity
Deakin University 
221 Burwood Hwy
Burwood, VIC 3125

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

03/12/2018

Approval date [1]

30/01/2019

Ethics approval number [1]

2018-386

Summary

Brief summary

Research has shown differences exist in gut bacteria between people with Parkinson’s disease and those without Parkinson’s disease. This research indicates that specific bacteria, capable of producing beneficial compounds called Short Chain Fatty Acids (SCFAs), are reduced in individuals with Parkinson’s disease. Additional research indicates that the start of Parkinson’s may be in the gut, where it then spreads toward the brain. We wish to investigate this further and want to see if people’s lifestyle factors, like diet, physical activity and sleep, contribute to the difference in gut bacteria between people with Parkinson’s, and people without Parkinson’s. For example, does higher levels of physical activity relate to better gut bacterial health? And how might this differ between the groups? Additionally, we wish to determine what relationship gut bacteria has to participants capability to think, termed cognition, and to participants ability to learn motor tasks, referred to as neuroplasticity, as both factors can be affected in Parkinson’s disease.

Overall, we aim to investigate if/how gut bacteria contributes to Parkinson’s disease progression and what impact lifestyle factors may have on this relationship. Specifically, the primary objective of this study is to assess if differences exist in terms of gut bacteria characteristics, meaning the types and amounts of gut bacteria present, across healthy young and healthy old groups and in PD. Additionally, the relationships between participants gut bacteria and scores of cognition and neuroplasticity will be assessed for any relationships that may indicate involvement of gut bacteria in these factors. Finally, lifestyle factors including diet, physical activity and sleep will be measured to see what effect they have on individuals gut bacteria. 
We expect there to be different gut bacteria characteristics across the groups, with lower amounts of specific and beneficial SCFA producing gut bacteria in the Parkinson’s disease individuals. In addition, we expect healthier lifestyles, based on the three factors measured, to relate to better gut bacteria characteristics, namely an increased number of SCFA producing bacteria. Cognition and neuroplasticity scores will be lower in the older adult groups, and we expect them to be less again in the PD group.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Helen Macpherson

Address

Deakin University
221 Burwood Highway, Burwood, VIC, 3125

Country

Australia

Phone

+61 3 924 45317

Fax

helen.macpherson@deakin.edu.au

Contact person for public queries

Name

Nathan Nuzum

Address

Deakin University
221 Burwood Highway, Burwood, VIC, 3125

Country

Australia

Phone

+61 419 426 566

Fax

n.nuzum@deakin.edu.au

Contact person for scientific queries

Name

Nathan Nuzum

Address

Deakin University
221 Burwood Highway, Burwood, VIC, 3125

Country

Australia

Phone

+61 419 426 566

Fax

n.nuzum@deakin.edu.au

Data sharing statement

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

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

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No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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