ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

Trial acronym

MPHFHT

Linked study record

Health condition

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

Cardiovascular disease

Heart failure

Heart transplant

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Oral and Gastrointestinal

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]

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]

Stool microbiome as assessed by 16S rRNA gene sequencing analysis of stool sample

Timepoint [1]

Stool sample provided at baseline (time zero) and 6 month follow-up.

Primary outcome [2]

Plasma short-chain fatty acids (SFCAs) as assessed by GCMS of plasma samples.

Timepoint [2]

Plasma samples provided at baseline (time zero) and 6 month follow-up.

Secondary outcome [1]

Medication usage as assessed by study-specific questionnaire.

Timepoint [1]

Study specific questionnaire completed at baseline (time zero).

Secondary outcome [2]

Diet in relation to changes in gut microbiome as assessed by study-specific questionnaire

Timepoint [2]

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

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

1/01/2020

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)

Recruitment hospital [1]

Fiona Stanley Hospital - Murdoch

Recruitment postcode(s) [1]

6150 - Murdoch

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Harry Perkins Institute of Medical Research

Address [1]

5 Robin Warren Dr, Murdoch WA 6150

Country [1]

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]

Individual

Name [1]

Natalie Ward

Address [1]

Medical Research Foundation, Royal Perth Hospital
Rear 50 Murray Street, Perth, 6000
Western Australia

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

SOUTH METROPOLITAN HEALTH SERVICE

Ethics committee address [1]

14 Barry Marshall Parade, Murdoch WA 6150

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

14/10/2019

Approval date [1]

13/11/2019

Ethics approval number [1]

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

Prof Girish Dwivedi

Address

Harry Perkins Institute of Medical Research
5 Robin Warren Dr, Murdoch WA 6150

Country

Australia

Phone

+61861511211

Fax

[email protected]

Contact person for public queries

Name

Adilah Ahmad

Address

Harry Perkins Institute of Medical Research
5 Robin Warren Dr, Murdoch WA 6150

Country

Australia

Phone

+61401506287

Fax

[email protected]

Contact person for scientific queries

Name

Adilah Ahmad

Address

Harry Perkins Institute of Medical Research
5 Robin Warren Dr, Murdoch WA 6150

Country

Australia

Phone

+61401506287

Fax

[email protected]

Data sharing statement

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

No/undecided IPD sharing reason/comment

Patient confidentiality and health care reasons

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
6051	Study protocol					378886-(Uploaded-05-12-2019-15-28-15)-Study-related document.docx
6052	Ethical approval					378886-(Uploaded-05-12-2019-15-29-09)-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

Source	Title	Year of Publication	DOI
Embase	Insights into the associations between the gut microbiome, its metabolites, and heart failure.	2023	https://dx.doi.org/10.1152/ajpheart.00436.2023

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically