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Trial registered on ANZCTR


Registration number
ACTRN12619001758190
Ethics application status
Approved
Date submitted
5/12/2019
Date registered
11/12/2019
Date last updated
11/12/2019
Date data sharing statement initially provided
11/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Gut flora profiling in heart failure patients
Scientific title
Microbiota Profile in Heart Failure and Heart Transplant
Secondary ID [1] 300020 0
None
Universal Trial Number (UTN)
Trial acronym
MPHFHT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular disease 315515 0
Heart failure 315516 0
Heart transplant 315553 0
Condition category
Condition code
Cardiovascular 313802 313802 0 0
Other cardiovascular diseases
Oral and Gastrointestinal 313841 313841 0 0
Normal oral and gastrointestinal development and function

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Heart failure is a chronic condition, with symptoms such as shortness of breath, fatigue, dizziness and oedema, and signs, such as increased venous pressure and pulmonary crackles, occurring when the heart cannot pump blood effectively around the whole body due to a weak or stiff heart muscle.

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] 316291 0
Not applicable
Comparator / control treatment
Healthy relatives of heart failure patients will be recruited as healthy environmental controls.
Control group
Active

Outcomes
Primary outcome [1] 322206 0
Stool microbiome as assessed by 16S rRNA gene sequencing analysis of stool sample
Timepoint [1] 322206 0
Stool sample provided at baseline (time zero) and 6 month follow-up.
Primary outcome [2] 322207 0
Plasma short-chain fatty acids (SFCAs) as assessed by GCMS of plasma samples.
Timepoint [2] 322207 0
Plasma samples provided at baseline (time zero) and 6 month follow-up.
Secondary outcome [1] 377720 0
Medication usage as assessed by study-specific questionnaire.
Timepoint [1] 377720 0
Study specific questionnaire completed at baseline (time zero).
Secondary outcome [2] 377721 0
Diet in relation to changes in gut microbiome as assessed by study-specific questionnaire
Timepoint [2] 377721 0
Study specific questionnaire completed at baseline (time zero).

Eligibility
Key inclusion criteria
Men and women between 40– 80 years of age presenting to Fiona Stanley Hospital with heart failure 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 heart failure
• Healthy participants will be relatives of heart failure 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
Gender
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
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)
WA
Recruitment hospital [1] 15422 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 28743 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 304474 0
Other Collaborative groups
Name [1] 304474 0
Harry Perkins Institute of Medical Research
Address [1] 304474 0
5 Robin Warren Dr, Murdoch WA 6150
Country [1] 304474 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] 304743 0
Individual
Name [1] 304743 0
Natalie Ward
Address [1] 304743 0
Medical Research Foundation, Royal Perth Hospital
Rear 50 Murray Street, Perth, 6000
Western Australia
Country [1] 304743 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304905 0
SOUTH METROPOLITAN HEALTH SERVICE
Ethics committee address [1] 304905 0
14 Barry Marshall Parade, Murdoch WA 6150
Ethics committee country [1] 304905 0
Australia
Date submitted for ethics approval [1] 304905 0
14/10/2019
Approval date [1] 304905 0
13/11/2019
Ethics approval number [1] 304905 0
RGS0000003481

Summary
Brief summary
In this study we aim to collect dental, saliva, blood and stool samples to characterise the gut microbiome profile of individuals with cardiovascular disease, specifically heart failure patients which include those requiring placement of a ventricular assist device or a heart transplant and compare their microbiome profile to that of healthy individuals. Individuals with cardiovascular disease will have an alteration in the composition and functionality of their gut microbiome compared to healthy individuals.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98602 0
Prof Girish Dwivedi
Address 98602 0
Harry Perkins Institute of Medical Research
5 Robin Warren Dr, Murdoch WA 6150
Country 98602 0
Australia
Phone 98602 0
+61861511211
Fax 98602 0
Email 98602 0
girish.dwivedi@perkins.uwa.edu.au
Contact person for public queries
Name 98603 0
Ms Adilah Ahmad
Address 98603 0
Harry Perkins Institute of Medical Research
5 Robin Warren Dr, Murdoch WA 6150
Country 98603 0
Australia
Phone 98603 0
+61401506287
Fax 98603 0
Email 98603 0
adilah.ahmadharithas@research.uwa.edu.au
Contact person for scientific queries
Name 98604 0
Ms Adilah Ahmad
Address 98604 0
Harry Perkins Institute of Medical Research
5 Robin Warren Dr, Murdoch WA 6150
Country 98604 0
Australia
Phone 98604 0
+61401506287
Fax 98604 0
Email 98604 0
adilah.ahmadharithas@research.uwa.edu.au

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?
Study protocol
Ethical approval
How or where can supporting documents be obtained?
Type [1] 6051 0
Study protocol
Citation [1] 6051 0
Link [1] 6051 0
Email [1] 6051 0
Other [1] 6051 0
Type [2] 6052 0
Ethical approval
Citation [2] 6052 0
Link [2] 6052 0
Email [2] 6052 0
Other [2] 6052 0
Summary results
No Results