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Trial registered on ANZCTR

Registration number

ACTRN12624000424505

Ethics application status

Approved

Date submitted

13/03/2024

Date registered

8/04/2024

Date last updated

18/08/2024

Date data sharing statement initially provided

8/04/2024

Type of registration

Prospectively registered

Titles & IDs

Public title

Mushrooms and their potential health effect on blood cholesterol

Scientific title

Investigating the effects of mushrooms compared to non-starchy vegetables on low-density lipoprotein cholesterol (LDL-C) in adults with mild hypercholesterolaemia – a randomised controlled cross-over trial

Secondary ID [1]

None

Universal Trial Number (UTN)

None

Trial acronym

Linked study record

Health condition

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

Hypercholesterolemia

Condition category

Condition code

Cardiovascular

Coronary heart disease

Cardiovascular

Other cardiovascular diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Mushroom intervention: 200 g of Agaricus bisporus white button mushrooms (raw weight) per day replacing 200 g of usual vegetable intake for 4 weeks.
Foods and supplements high in beta-glucan or other substances that may affect cholesterol levels will be excluded from the diet and replaced with suitable alternatives (e.g. oats at breakfast could be replaced with cereal flakes or pearl barley could be replaced by brown rice).
At the beginning of the mushroom intervention phase during a ~25 min in-person consultation with a research dietitian/nutritionist, either at the baseline or visit 3, the participant will be provided with tailored advice (based on their usual diet) about how to include the mushrooms into their usual diet. Participants will also be provided with an instruction manual including information about the study design, the diet protocol, purchasing of mushrooms, monitoring of compliance, foods to avoid and alternatives, cooking ideas, recipes and frequently asked questions.
Participants will be provided with a voucher to purchase mushrooms weekly from a local supermarket chain (Coles Supermarket, that have stores spread out across Adelaide). The instruction manual will include clear instructions of where and the type of mushrooms to purchase. Note, mushrooms sold at all Coles stores in Adelaide are supplied by one mushroom producer.
To assess compliance, participants will complete a daily log about their consumption of mushrooms and excluded foods. The information will also be logged via a weekly online survey.
A cross-over study design will be followed. Washout period in-between interventions will be two weeks.

Intervention code [1]

Treatment: Other

Intervention code [2]

Lifestyle

Comparator / control treatment

Control intervention: 200 g of non-starchy vegetables per day replacing 200 g of normal vegetable intake excluding mushrooms.
Foods and supplements high in beta-glucan or other substances that may affect cholesterol levels will be excluded from the diet and replaced with suitable alternatives (the same alternatives as for the mushroom intervention).
At the beginning of the control intervention phase during a ~25 min in-person consultation with a research dietitian/nutritionist, either at the baseline or visit 3, the participant will be provided with tailored advice (based on their usual diet) about how to include non-starchy vegetables into their usual diet. Participants will also be provided with an instruction manual including information about the study design, the diet protocol, purchasing of non-starchy vegetables including a list of vegetable options, monitoring of compliance, foods to avoid and alternatives, cooking ideas, recipes and frequently asked questions.
Participants will be provided with a voucher to purchase non-starchy vegetables weekly from a local supermarket chain (Coles Supermarket, that have stores spread out across Adelaide). The instruction manual will include clear instructions of where and the type of vegetables to purchase.
To assess compliance, participants will complete a daily log about their consumption of non-starch vegetables and excluded foods. The information will also be logged via a weekly online survey.
A cross-over study design will be followed. Washout period in-between interventions will be two weeks.

Control group

Active

Outcomes

Primary outcome [1]

Low-density lipoprotein cholesterol (LDL-C)

Timepoint [1]

Baseline and end of each intervention period: visits 1 (day 0), 2 (day 28±3, primary timepoint), 3 (day 42±3) and 4 (day 70±3, primary timepoint) post commencement of dietary intervention.

Secondary outcome [1]

Total cholesterol

Timepoint [1]

Baseline and end of each intervention period: visits 1 (day 0), 2 (day 28±3), 3 (day 42±3) and 4 (day 70±3) post commencement of dietary intervention

Secondary outcome [2]

High-density lipoprotein cholesterol (HDL-C)

Timepoint [2]

Baseline and end of each intervention period: visits 1 (day 0), 2 (day 28±3), 3 (day 42±3) and 4 (day 70±3) post commencement of dietary intervention

Secondary outcome [3]

Triglycerides

Timepoint [3]

Baseline and end of each intervention period: visits 1 (day 0), 2 (day 28±3), 3 (day 42±3) and 4 (day 70±3) post commencement of dietary intervention

Secondary outcome [4]

Non-HDL-C

Timepoint [4]

Baseline and end of each intervention period: visits 1 (day 0), 2 (day 28±3), 3 (day 42±3) and 4 (day 70±3) post commencement of dietary intervention

Secondary outcome [5]

Total cholesterol : HDL-C ratio

Timepoint [5]

Baseline and end of each intervention period: visits 1 (day 0), 2 (day 28±3), 3 (day 42±3) and 4 (day 70±3) post commencement of dietary intervention

Secondary outcome [6]

Dietary intake

Timepoint [6]

Two 24-hour recalls will be completed before commencement of dietary intervention (day -7 - -1); end of 1st intervention phase (days 21-27 post commencement of dietary intervention); end of washout period (days 35-41 post commencement of dietary intervention); end of 2nd intervention phase (days 63-69 post commencement of dietary intervention)

Secondary outcome [7]

Body mass index (BMI)

Timepoint [7]

Baseline and end of each intervention period: visits 1 (day 0), 2 (day 28±3), 3 (day 42±3) and 4 (day 70±3) post commencement of dietary intervention

Secondary outcome [8]

Participant perceptions and experience of the mushroom intervention.

Timepoint [8]

End of mushroom intervention period: visits 2 (day 28±3 post commencement of dietary intervention), and 4 (day 70±3 post commencement of dietary intervention)

Secondary outcome [9]

Safety outcome: vital signs (blood pressure, heart rate, respiratory rate, temperature)

Timepoint [9]

Baseline and end of each intervention period: visits 1 (day 0), 2 (day 28±3), 3 (day 42±3) and 4 (day 70±3) post commencement of dietary intervention

Secondary outcome [10]

Safety outcome: Adverse events

Timepoint [10]

Throughout the intervention with follow-up at each study visit: visits 2 (day 28±3), 3 (day 42±3) and 4 (day 70±3) post commencement of dietary intervention

Secondary outcome [11]

Safety outcome: Concomitant medications

Timepoint [11]

Throughout the intervention with follow-up at each study visit: visits 2 (day 28±3), 3 (day 42±3) and 4 (day 70±3) post commencement of dietary intervention,

Eligibility

Key inclusion criteria

INCLUSION CRITERIA:
1. Willing and able to provide written Informed Consent
2. Access to a personal email inbox
3. Male or Female individuals
4. Aged > or equal to 18 & <66 years of age at clinic screening
5. BMI > or equal to 18.5 kg/m2 and <35 kg/m2 at time of clinic screening
6. Low cardiovascular disease (CVD) risk score in individuals aged > or equal to 45 years of <5% estimated 5-year CVD risk determined using the Australian CVD risk calculator (cvdcheck.org.au)
7. Fasting LDL-cholesterol > or equal to 3.0 mmol/L and < or equal to 5 mmol/L confirmed at clinic screening (plasma)
8. Have access to a Coles supermarket
9. Ability to refrigerate mushrooms/vegetables and have the facilities to prepare and cook them

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

EXCLUSION CRITERIA:
1. Use of and not prepared to abstain from marine and algae derived omega-3 supplements at high dose (>900 mg/day of docosahexaenoic acid (DHA) / eicosapentaenoic acid (EPA)) or marine and algae derived omega 3 fortified foods that may, in the opinion of the PI or designee, affect lipid concentrations, within the 84 days of Day 0
2. Use of lipid lowering medications (e.g. statins, metformin, fibrates, cholesterol absorption inhibitors, nicotinic acid) or lipid raising medications (eg. Beta blockers, steroids, amiodarone, diuretics) within 28 days of Day 0.
3. Use of and not prepared to abstain from supplements, or foods containing ß-glucan (oats, barley, rye, nutritional yeast, mushrooms other than study mushrooms) or other substances (e.g. psyllium, plant sterol fortified foods and supplements, curcumin, turmeric) that may, in the opinion of the PI or designee, affect lipid concentrations within 14 days of Day 0
4. Previous diagnosis of chronic disease such as CVD, diabetes
(Type I, Type II, and/or Gestational Diabetes), cancer, familial hypercholesterolaemia, kidney disease, liver disease
5. Smoking (i.e., history of smoking within the last six months)
6. Serum triglycerides >4.5mmol/L (LDL-cholesterol concentrations are unreliable in the presence of high triglyceride levels) confirmed at clinic screening (using capillary plasma)
7. Hypertension (blood pressure > or equal to 140/90mmHg)
8. Suspected aversion and/or intolerance to mushrooms
9. Unwilling or unable to maintain usual levels of physical activity or dietary intake for the duration of the study
10. Currently pregnant and/or nursing (lactating), self-reported by the applicant
11. Currently hospitalised or any planned hospitalisations during the study that may affect the applicant’s ability to comply with the study in the opinion of the PI or designee
12. Received an investigational drug within 90 days of Day 0, that in the opinion of the PI or designee may affect the outcome of the study
13. Unable to comply, experience distress with study procedures, or has a medical condition and/or receiving medical treatments (including medications) that in the opinion of the PI or designee, may affect the outcome of the study
14. Travel which may interfere with complying to the study diet guidelines

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation is not concealed.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Simple randomisation using a randomisation table created by computer software.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Crossover

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

A sample size of 42 participants will provide 80% statistical power at a=0.05 (two-tailed) and account for a dropout rate of 20%, to detect an LDL-C effect size of ~0.25 mmol/L,
Prior to database lock, a final detailed Statistical Analysis Plan (SAP) will be available.
In brief, statistical analysis will be performed using SPSS software. Comparisons between interventions for continues outcome variables will be analysed using linear mixed models for repeated measures. In cases where significant intervention x time interactions are observed post-hoc analyses with Bonferroni adjustments will be conducted. The data will be examined for interaction effects due to the order in which the meals were consumed. A p-value <0.05 will be considered significant.

Recruitment

Recruitment status

Withdrawn

Reason for early stopping/withdrawal

Lack of funding/staff/facilities

Date of first participant enrolment

Anticipated

8/04/2024

Actual

Date of last participant enrolment

Anticipated

30/08/2024

Actual

Date of last data collection

Anticipated

29/11/2024

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

CSIRO Nutrition & Health Research Clinic - Adelaide

Recruitment postcode(s) [1]

5000 - Adelaide

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Horticultural Innovation

Address [1]

Country [1]

Australia

Primary sponsor type

Government body

Name

Commonwealth Scientific and Industrial Research Organisation (CSIRO)

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

CSIRO Health and Medical Human Research Ethics Committee

Ethics committee address [1]

https://www.csiro.au/en/about/Policies/Ethical-human-research

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

14/11/2023

Approval date [1]

05/02/2024

Ethics approval number [1]

2023_068_HREC

Summary

Brief summary

Reducing blood cholesterol is one of the key strategies to reduce cardiovascular disease risk (CVD), the leading cause of mortality worldwide. While the evidence for the cholesterol lowering effects of ß-glucan from oats and barley are well established, there is less evidence for ß-glucan from other dietary sources such as fungi, yeast and algae. 
The aim of the current study is to investigate the effects of consuming 200 g/day of white button mushrooms (Agaricus bisporus) (raw weight) on serum LDL-cholesterol in adults with mild hypercholesterolaemia compared to 200 g/day non-starchy vegetables over four weeks.

Trial website

The trial website is still under development

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Welma Stonehouse

Address

CSIRO, South Australian Medical Research Institute Building, North Terrace, Adelaide SA 5000

Country

Australia

Phone

+61 08 83038919

Fax

[email protected]

Contact person for public queries

Name

Brooke Wymond

Address

CSIRO, South Australian Medical Research Institute Building, North Terrace, Adelaide SA 5000

Country

Australia

Phone

+61 08 83038856

Fax

[email protected]

Contact person for scientific queries

Name

Welma Stonehouse

Address

CSIRO, South Australian Medical Research Institute Building, North Terrace, Adelaide SA 5000

Country

Australia

Phone

+61 08 83038919

Fax

[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?

All of the individual participant data collected during the trial, after de-identification.

When will data be available (start and end dates)?

Following publication, no end date

Available to whom?

Researchers who request access to the data and provide a proposal with sound rationale and methodology and pending Principal Investigator and Human Research Ethics Committee approval.

Available for what types of analyses?

Any purpose.

How or where can data be obtained?

CSIRO Data Access Portal (DAP) - access is subject to CSIRO and Human Research Ethics Commitee approval. Access to the portal may be requested by emailing the principal investigator ([email protected]).

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
21854	Analytic code			[email protected]
21855	Data dictionary			[email protected]

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.

Trial Review

Documents added manually

Documents added automatically