Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000891729
Ethics application status
Approved
Date submitted
20/06/2022
Date registered
22/06/2022
Date last updated
15/09/2023
Date data sharing statement initially provided
22/06/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The SAUNA Study: a blood- and stool-based investigation of markers correlating with hallmarks of dementia
Scientific title
SAHMRI Autophagy in Amyloidosis (SAUNA) Study: a blood- and stool-based investigation of markers correlating with hallmarks of dementia
Secondary ID [1] 307223 0
Nil known
Universal Trial Number (UTN)
Trial acronym
SAHMRI Autophagy in Amyloidosis (SAUNA) Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dementia 326639 0
Autophagy 326640 0
Condition category
Condition code
Neurological 323882 323882 0 0
Dementias

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Study design: A cross-sectional study. The exposure will be participants who test positive for amyloid plaques, and the comparator group will be participants who test negative for amyloid plaques. This study will be utilising an existing workflow/recruitment regime, and will not be assigning any form of treatment to individuals. Rather, the study will be recruiting participants as they enroll into the ADNeT program.

Primary aim: to understand if a cellular recycling process called autophagy is different in people who have the molecular hallmarks of Alzheimer’s disease compared with people who do not.
Secondary aim: To determine if the gut microbiome composition and structure, measured in stool samples, is altered in people who have the molecular hallmarks of Alzheimer’s disease.

Setting: The study is a cross-sectional study that will recruit participants from the Australian Dementia Network (ADNet) - Screens and Trials Ready Cohort (TRC). The ADNet TRC is a phase I, multiple site open label study that aims to recruit individuals who have expressed an interest in being involved in dementia research and/or clinical trials to test interventions for Alzheimer's disease and other neurodegenerative diseases causing dementia. Only participants from the South Australian Health and Medical Research Institute (SAHMRI) site in South Australia will be invited to participate in this study.

Recruitment/screening: 160 male and female individuals, of at least 40 years of age, who have been recruited into the ongoing ADNet TRC study. These people will be cognitively intact and will not meet criteria for mild cognitive impairment or dementia.

Blood collection: Venepuncture will be performed as part of the ADNet TRC study. An additional blood collection will be sampled for the SAUNA study during the same venepuncture procedure.

Stool collection: Faecal samples will be entirely optional and not a requirement following blood collection. Willing participants will be provided with a stool collection kit, and will be instructed on how to collect a stool sample by an experienced and qualified staff member. It will be stressed to participants that they are not required to provide a stool sample if they choose to provide blood samples, and that it is an entirely optional and additional investigation. Willing participants will also be provided with a pre-paid postage envelope, so that they may collect their stool sample independently, within the privacy and comfort of their own home, and securely and privately post their samples to the research laboratory, within one week of blood collection.

Randomisation: No randomisation will be performed as this is a cross-sectional study and group membership will be determined according to whether participants have positive amyloid beta PET scans during the ADNet TRC.

Autophagic flux measurement:
Blood samples will be processed immediately after collection for measurement of autophagic flux according to the method developed by our group. Autophagic flux will be determined by the difference in the accumulation of LC3BII over time between blocked and unblocked samples (i.e. what should have been degraded during the one-hour incubation) using the equation deltaLC3II = LC3II+CQ – LC3II-CQ. Autophagic flux will be compared between groups of amyloid positive and amyloid negative individuals.

Plasma hormones, amino acids and lipids:
Plasma will be snap frozen at -80C, for later assessment of blood glucose, insulin, blood lipids, free fatty acids, glucose regulating hormones (e.g.: insulin, C-peptide, adiponectin), inflammatory cytokines (e.g.: C-reactive protein), and appetite-regulating hormones (eg: GLP-1, GIP, Ghrelin) using commercially available kits. Plasma amino acids may be analysed by mass spectrometry. Samples will be compared between groups of amyloid positive and amyloid negative individuals.

Gut microbiome characterisation:
Stool samples will be provided by participants in the comfort and privacy of their own home through the use of stool nucleic acid collection and preservation tubes (Norgen, Biotek, Canada). Stabilised samples will be collected from participants via pre-paid post for sample processing, metagenomic sequencing, and whole genome sequencing, which will be performed at the SAHMRI Microbiome Research Laboratory, using established protocols. Briefly, DNA extraction will be performed, prior to 150 bp paired-end metagenomic shotgun sequencing using the Illumina HiSeq system at the SAHMRI Genomics Core. Sequences will be filtered, human-derived reads removed and destroyed. Importantly, no human DNA sequence that is generated by microbiome characterisation will be analysed as a part of this study. Microbiome characteristics will be compared between groups of amyloid positive and amyloid negative individuals.

Additional data from ADNet TRC
Data collected from ADNet may be used by the SAUNA study to aid interpretation of autophagy measurement in this cohort. This may include age, sex, weight/BMI, data taken from medical history, eligibility assessment, alcohol use tests, memory complaint instruments, mood indexes and scales, sleep indexes and questionnaires, functional independence questionnaires, physical activity questionnaires, diet questionnaires, neuropsychological and cognitive assessment, MRI, amyloid beta PET, and tau PET. Data collected will from recruitment up to 2 years post-enrolment.
Intervention code [1] 323779 0
Not applicable
Comparator / control treatment
Participants who test negative for amyloid plaques.
Control group
Active

Outcomes
Primary outcome [1] 331697 0
Changes in autophagic flux, determined by the accumulation of LC3II measured in blood samples of individuals with and without amyloid beta plaques.
Timepoint [1] 331697 0
At enrolment
Secondary outcome [1] 410815 0
Changes in ß-hexosaminidase activity, measured by enzyme activity assays in blood samples of individuals with and without amyloid beta plaques.
Timepoint [1] 410815 0
At enrolment
Secondary outcome [2] 410816 0
Changes in microbial biodiversity, measured in stool samples, between individuals with and without amyloid beta plaques.
Timepoint [2] 410816 0
At enrolment
Secondary outcome [3] 411073 0
Changes in amino acids/cytokines, measured in blood plasma samples, between individuals with and without amyloid beta plaques.
Timepoint [3] 411073 0
At enrolment

Eligibility
Key inclusion criteria
1. Expressed interest in participation in interventions trials or dementia research projects
2. Age 40 years or older
3. English speaking
4. At least 7 years or more of education
5. Adequate visual and auditory acuity to complete neuropsychological testing
6. Reliable caregiver or study partner capable of providing correct information about the patient’s history and clinical symptoms
7. MMSE score of 15 or higher
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Lifetime history of schizophrenia, schizoaffective disorder, or unstable bipolar disorder
2. Current significant or unstable depression
3. Current drug or alcohol abuse/dependence
4. History of alcohol abuse/dependence within 2 years of the onset of the symptoms of dementia or cognitive impairment
5. History of cancer (other than in-situ skin or in-situ prostate cancer) within the previous 2 years
6. Any significant disease or unstable medical condition that could affect neuropsychological testing (i.e., chronic renal failure, chronic hepatic disease, severe pulmonary disease)
7. Contraindications to brain magnetic resonance imaging (MRI) including, but not limited to, those with a pacemaker, presence of metallic fragments near the brain, eyes or spinal cord, or cochlear implant*
*Participants contraindicated for MRI who have previously been enrolled in longitudinal dementia research cohorts (e.g. AIBL, PISA, etc.) are excepted from this exclusion criterion

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
This is a pilot study, and since it is the first time autophagic flux will be measured in a human cohort that investigates autophagy with regards to amyloid plaque burden, a proper power calculation is technically not possible. However, based on prior experiments conducted when investigating this method in people with atherosclerosis, we can estimate an inter-individual variability and an expected change. We have previously observed that people with stable atherosclerosis had on average 3.1 fold more autophagy than people with unstable atherosclerosis (myocardial infarction). For autophagic flux measurements taken from 28 control individuals, the standard deviation (SD) measured was 0.202.
We are expecting a two-fold decrease in autophagy in people with amyloid plaques compared with people who do not have amyloid plaques. Positivity for amyloid plaques will be determined based on PET imaging for Aß (the scan will be read as positive when there is visual evidence of increased tracer binding in more than one of the following areas – inferior frontal cortex, lateral parietal cortex, precuneus/posterior cingulate gyrus region or lateral or medial temporal cortex).
With an alpha risk of 0.05 and a power of 0.8 we would need 160 participants to detect a difference of a two-fold reduction in autophagy in amyloid-positive people using a t test.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/06/2022
Actual
2/09/2022
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
30/06/2025
Actual
Sample size
Target
160
Accrual to date
32
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 22555 0
South Australian Health and Medical Research Institute (SAHMRI) - Adelaide
Recruitment postcode(s) [1] 37804 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 311521 0
Other Collaborative groups
Name [1] 311521 0
South Australian Health and Medical Research Institute (SAHMRI)
Country [1] 311521 0
Australia
Funding source category [2] 311637 0
Charities/Societies/Foundations
Name [2] 311637 0
Dementia Australia Research Foundation
Country [2] 311637 0
Australia
Primary sponsor type
Other Collaborative groups
Name
South Australian Health and Medical Research Institute (SAHMRI)
Address
SAHMRI, North Terrace, Adelaide SA 5000 Australia.
PO Box 11060, Adelaide SA 5001
Country
Australia
Secondary sponsor category [1] 313076 0
University
Name [1] 313076 0
University of Adelaide
Address [1] 313076 0
The University of Adelaide, Level 4, Rundle Mall Plaza, 50 Rundle Mall, Adelaide, SA 5000.
Australia
Country [1] 313076 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310980 0
University of Adelaide Human Research Ethics Committee
Ethics committee address [1] 310980 0
Ethics committee country [1] 310980 0
Australia
Date submitted for ethics approval [1] 310980 0
Approval date [1] 310980 0
07/06/2022
Ethics approval number [1] 310980 0
H-2022-036

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

Contacts
Principal investigator
Name 119574 0
Dr Timothy Sargeant
Address 119574 0
Lysosomal Health in Ageing, Hopwood Centre for Neurobiology, Lifelong Health, South Australian Health and Medical Research Institute.
North Terrace, Adelaide
SA 5000.
Country 119574 0
Australia
Phone 119574 0
+61 0426827689
Fax 119574 0
Email 119574 0
[email protected]
Contact person for public queries
Name 119575 0
Timothy Sargeant
Address 119575 0
Lysosomal Health in Ageing, Hopwood Centre for Neurobiology, Lifelong Health, South Australian Health and Medical Research Institute.
North Terrace, Adelaide
SA 5000.
Country 119575 0
Australia
Phone 119575 0
+61 0426827689
Fax 119575 0
Email 119575 0
[email protected]
Contact person for scientific queries
Name 119576 0
Timothy Sargeant
Address 119576 0
Lysosomal Health in Ageing, Hopwood Centre for Neurobiology, Lifelong Health, South Australian Health and Medical Research Institute.
North Terrace, Adelaide
SA 5000.
Country 119576 0
Australia
Phone 119576 0
+61 0426827689
Fax 119576 0
Email 119576 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data underlying published results, after de-identification.
When will data be available (start and end dates)?
Immediately following publication, no end date.
Available to whom?
Case-by-case basis at the discretion of the Primary Sponsor.
Available for what types of analyses?
For purposes linked to the aims in the approved proposal, and for meta-analyses.
How or where can data be obtained?
Access subject to approvals by the Principal Investigator ([email protected]).


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.