Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001727134
Ethics application status
Approved
Date submitted
21/11/2019
Date registered
9/12/2019
Date last updated
3/03/2020
Date data sharing statement initially provided
9/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Gut flora profiling in people with cardiovascular disease
Scientific title
Microbiota Profile in Acute Coronary Syndrome
Secondary ID [1] 299879 0
Nil known
Universal Trial Number (UTN)
Trial acronym
MPACS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cardiovascular disease 315289 0
Condition category
Condition code
Cardiovascular 313590 313590 0 0
Coronary heart disease
Cardiovascular 313591 313591 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Acute coronary syndrome (ACS) is a set of symptoms, such as chest pain, nausea and
sweating, caused from decreased blood flow in the coronary arteries which supply
blood to the heart. It is the unstable form of cardiovascular disease (CVD). Chronic stable angina, on the other hand, has similar symptoms, but these symptoms ease with rest, unlike ACS. So, chronic stable angina is the stable form of this CVD.

The aim of this study is to profile the gut microbiome, from dental scrapings, saliva, blood and faecal samples in people with acute coronary syndrome, chronic stable angina and healthy individuals. This is important as many studies have established that normal people have a certain gut microbiome profile compared to people with cardiovascular disease. In addition to gut microbiome profiling, the information gathered from the results of this study may be beneficial in a clinical setting. Given the prevalence of cardiovascular disease and the large interest in the microbiome field, the findings of this study will allow a greater understanding of the role of the microbiome in cardiovascular disease, which will have important clinical implications. It may also facilitate the future development of different therapeutic strategies to target and/or change the microbiome, which will be explored through intervention studies.

Dental, stool, saliva and blood samples will be obtained in the hospital at baseline (time zero) and again at follow-up (6 months).
Intervention code [1] 316144 0
Not applicable
Comparator / control treatment
Healthy relatives of acute coronary syndrome and chronic stable angina groups will be recruited as healthy environmental controls.
Control group
Active

Outcomes
Primary outcome [1] 322041 0
Stool microbiome as assessed by 16S rRNA gene sequencing analysis of stool sample
Timepoint [1] 322041 0
Stool sample provided at baseline (time zero) and 6 month follow-up.
Primary outcome [2] 322127 0
Plasma short-chain fatty acids (SFCAs) as assessed by GCMS of plasma samples
Timepoint [2] 322127 0
Plasma samples provided at baseline (time zero) and 6 month follow-up.
Secondary outcome [1] 377134 0
Medication usage as assessed by study-specific questionnaire
Timepoint [1] 377134 0
Study specific questionnaire completed at baseline (time zero).
Secondary outcome [2] 377434 0
Diet in relation to changes in gut microbiome as assessed by study-specific questionnaire
Timepoint [2] 377434 0
Study specific questionnaire completed at baseline (time zero).

Eligibility
Key inclusion criteria
Men and women between the age of 40– 80 years of age presenting to FSH with acute
coronary syndrome or chronic stable angina will be recruited for the study. Healthy family
members of patients will be invited to take part in the study and will act as environmental
controls and will be age matched where possible.
Inclusion criteria:
• The participant to present to FSH with acute coronary syndrome or chronic stable
angina.
• Healthy participants will be relatives of ACS patients and are defined as individuals
with no clinically relevant abnormalities identified by a detailed medical history, full
physical examination including blood pressure, heart rate, clinical lab tests from a
fasting blood sample
• Evidence of a personally signed and dated informed consent document indicating that
the participant has been informed of all pertinent aspects of the trial
• Willing and able to comply with study procedures, i.e. sample collection
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants will be excluded from the study:
• If there are circumstances that interfere with the participant’s ability to give informed
consent (e.g. diminished understanding, or proficiency in English language and an
interpreter unavailable)
• Participants taking probiotics, antibiotics or antivirals which may disrupt gut
microbiota environment, current or recent <3 months.
• Major chronic disease e.g. cancer or dementia
• Healthy participants will be excluded if they have a history of major chronic disease
(including cardiovascular disease, psychiatric illness, cancer, diabetes), BMI <18 or
>35 kg/m2, current or recent (<12 months) smoking, current or recent (<6 months)
significant weight loss or gain (>6% body weight), alcohol intake >280g p/week for
men and >210g p/week for women.
• Inability to comply with study procedure

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
The primary outcome will be assessed from the stool and plasma samples collected for batch analysis at the completion of the study. All stool samples will undergo 16S rRNA analysis for microbiome profiling. DNA will be isolated from the sample using QIAamp Fast DNA Mini Kit and subsequent 16S rRNA gene sequencing performed using the MiSeq desktop sequencer (Illumina) with microbiome analysis conducted using SILVAngs pipeline data analysis and The R project for Statistical Computing (version 3.2.4), as previously described (Caparros-Martin et al, 2017). Analysis will include; multivariate analysis to determine diet clusters and gut community composition in response to the different diets, diversity indexes to determine the diversity and dominance of gut bacteria, microbial taxonomic composition by phylum and family, and Tax4Fun analysis, a prediction tool to infer the functional capabilities of the bacterial community. To investigate the functional significance of alterations in the microbiome patterns and gain insight into the mechanistic handle linking the microbiome coronary health axis, we will utilise virtual metagenomics and function software platforms. In addition, products of bacterial digestion including plasma and stool SCFAs, TMAO and BAs will be analysed using in house GCMS methods. In the final analysis, participants with ACS will be age matched with healthy controls.
Secondary outcomes will be associations with family history, medication use, diet and
clinical outcomes. These will be done using patient medical records and discharge notes, a
validated food frequency questionnaire to ascertain macro and micronutrient intake and
patient follow-up. All ACS patients will be followed up at 6 months when they present to the
Department of Cardiology, where updated information on medication use, blood pressure and clinical outcomes will be gathered, in addition to follow up dental, oral, blood and stool
samples for analysis of microbiota profile, SCFA, TMAO and BA. This will allow us to
determine if microbiota composition and functionality stabilises as the disease status
stabilises.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
9/03/2020
Actual
Date of last participant enrolment
Anticipated
1/07/2021
Actual
Date of last data collection
Anticipated
1/07/2024
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 15279 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 28589 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 304338 0
Other Collaborative groups
Name [1] 304338 0
Harry Perkins Institute of Medical Research
Country [1] 304338 0
Australia
Primary sponsor type
Individual
Name
Girish Dwivedi
Address
Harry Perkins Institute of Medical Research
5 Robin Warren Dr, Murdoch WA 6150
Country
Australia
Secondary sponsor category [1] 304586 0
Individual
Name [1] 304586 0
Natalie Ward
Address [1] 304586 0
Medical Research Foundation, Royal Perth Hospital
Rear 50 Murray Street, Perth, 6000
Western Australia
Country [1] 304586 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304789 0
South Metropolitan Health Service
Ethics committee address [1] 304789 0
Ethics committee country [1] 304789 0
Australia
Date submitted for ethics approval [1] 304789 0
01/04/2019
Approval date [1] 304789 0
11/10/2019
Ethics approval number [1] 304789 0
RGS0000003402

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

Contacts
Principal investigator
Name 98210 0
Prof Girish Dwivedi
Address 98210 0
Harry Perkins Institute of Medical Research
5 Robin Warren Dr, Murdoch WA 6150
Country 98210 0
Australia
Phone 98210 0
+61861511211
Fax 98210 0
Email 98210 0
[email protected]
Contact person for public queries
Name 98211 0
Adilah Ahmad
Address 98211 0
Harry Perkins Institute of Medical Research
5 Robin Warren Dr, Murdoch WA 6150
Country 98211 0
Australia
Phone 98211 0
+61401506287
Fax 98211 0
Email 98211 0
[email protected]
Contact person for scientific queries
Name 98212 0
Adilah Ahmad
Address 98212 0
Harry Perkins Institute of Medical Research
5 Robin Warren Dr, Murdoch WA 6150
Country 98212 0
Australia
Phone 98212 0
+61401506287
Fax 98212 0
Email 98212 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
Patient confidentiality and health care reasons


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
5798Study protocol    378788-(Uploaded-02-03-2020-10-58-44)-Study-related document.docx
5799Ethical approval    378788-(Uploaded-02-03-2020-11-01-16)-Study-related document.pdf



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.