ANZCTR - Registration

Registration number

ACTRN12618000283279

Ethics application status

Approved

Date submitted

9/02/2018

Date registered

23/02/2018

Date last updated

23/02/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

A double blind, randomized, placebo controlled, cross-over trial investigating the effect of High Amylose Maize Starch (HAMS) supplementation on fecal microbiological and inflammatory outcomes in individuals with Cystic Fibrosis and Healthy Volunteers.

Scientific title

A double blind, randomized, placebo controlled, cross-over trial investigating the effect of High Amylose Maize Starch (HAMS) supplementation on fecal microbiological and inflammatory outcomes in individuals with Cystic Fibrosis and Healthy Volunteers.

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

CF HAMS STUDY

Linked study record

Health condition

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

Cystic Fibrosis

Condition category

Condition code

Respiratory

Other respiratory disorders / diseases

Human Genetics and Inherited Disorders

Cystic fibrosis

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Participants will be asked to consume prepacked 40g/d high amylose maize starch (HAMS) or 40g/day regular maize starch (RMS - Placebo) in a cross over fashion. Participants will consume the investigational product for 2 weeks, followed by a 2 week wash out prior to completing 2 further weeks of the alternate product.

Each participant will act as their own control and the CF group will be compared to a Healthy control group undergoing the same intervention.

HAMS is a well-described food supplement which contains approximately 70% amylose. It is used in a variety of food applications. It is generally regarded as safe (GRAF) by the FDA and has been used in healthy participants in clinical trials.
HAMS and RMS will be provided in pre-packaged sachets. Participants will be asked to mix the supplement with 250 mL of liquid (for example milk, orange juice or water) and consume 40g/d in single, or in 2 divided doses.
The resistant starch to be used is a standard food additive which is widely used globally. The constituents will be drug or food grade and supplied as follows:
• HAMS = Hylon VII from Ingredion
• RMS/Placebo = Mazaca 3401X from Ingredion,
Both are drug grade products as specified by WHO and sourced by GD Pharma, a sterile pharmaceutical facility with TGA and cGMP accreditation.

Adherence to the intervention will be monitored via packets returned at each visit. This will be monitored by both the dispensing pharmacy and the study coordinators

Intervention code [1]

Treatment: Other

Comparator / control treatment

Participants will be asked to consume prepacked 40g/d high amylose maize starch (HAMS) or 40g/day regular maize starch (RMS - Placebo) in a cross over fashion. Participants will consume the investigational product for 2 weeks, followed by a 2 week wash out prior to completing 2 further weeks of the alternate product.

Each participant will act as their own control and the CF group will be compared to a Healthy control group undergoing the same intervention.

HAMS is a well-described food supplement which contains approximately 70% amylose. It is used in a variety of food applications. It is generally regarded as safe (GRAF) by the FDA and has been used in healthy participants in clinical trials.
HAMS and RMS will be provided in pre-packaged sachets. Participants will be asked to mix the supplement with 250 mL of liquid (for example milk, orange juice or water) and consume 40g/d in single, or in 2 divided doses.
The resistant starch to be used is a standard food additive which is widely used globally. The constituents will be drug or food grade and supplied as follows:
• HAMS = Hylon VII from Ingredion
• RMS/Placebo = Mazaca 3401X from Ingredion,
Both are drug grade products as specified by WHO and sourced by GD Pharma, a sterile pharmaceutical facility with TGA and cGMP accreditation.

Adherence to the intervention will be monitored via packets returned at each visit. This will be monitored by both the dispensing pharmacy and the study coordinators

Control group

Placebo

Outcomes

Primary outcome [1]

The primary outcome will be to determine whether supplementation with HAMS improves dysbiosis in the CF gut compared with regular maize starch as assessed by V4 paired-read 16S ribosomal RNA gene sequencing, and sequence bioinformatic processing.

Timepoint [1]

This will be measured after 2 weeks (day 14) of HAMS/RMS supplementation and compared with a baseline measurement taken at time point 0

Primary outcome [2]

The co-primary outcome will be to determine whether supplementation with HAMS increases fecal and blood SCFA levels, compared with regular maize starch.

Timepoint [2]

This will be measured after 2 weeks (day 14) of HAMS/RMS supplementation and compared with a baseline measurement taken at time point 0

Secondary outcome [1]

Secondary outcomes include tolerability of supplementation, as assessed by GI symptoms questionnaires including the CFQ-R and the PROMIS questionnaires.

Timepoint [1]

This will be measured after 2 weeks (day 14) of HAMS/RMS supplementation and compared with a baseline measurement taken at time point 0

Secondary outcome [2]

Changes in metabolic markers as assessed by serum and stool levels of SCFAs, microbe synthesised vitamins, metabolic (fecal calproectin, CRP, white cell differential) and inflammatory markers (Interleukins including IL-17, 22, 10, 6, 6 and 1). This is a composite outcome.

Timepoint [2]

This will be measured after 2 weeks (day 14) of HAMS/RMS supplementation and compared with a baseline measurement taken at time point 0

Eligibility

Key inclusion criteria

CF participants who meet all of the following inclusion criteria will be eligible:
1. Participated in the CF DYSBIOSIS study AND:
2. Subjects aged 18 years or older with a diagnosis of CF as defined by:
a. Presence of known CF causing genetic mutations in the CFTR OR
b. Sweat chloride value >60 mmol/L OR
c. Sweat chloride value <60 mmol/L must have documented evidence of chronic sinopulmonary disease manifested by (but not limited to):
i. Persistent colonization/infection with typical CF pathogens, including Staphylococcus aureus, Haemophilus influenzae, and mucoid and nonmucoid Pseudomonas aeruginosa
ii. Chronic cough and sputum production
iii. Persistent chest radiograph abnormalities
3. Nasal polyps, chronic sinusitis
4. Able to provide informed consent.
5. Willing and able to provide a stool sample and record a diet history.
6. Stable CF disease as judged by the investigator.

Healthy control participants who meet all of the following inclusion criteria will be eligible:
1. Participation in the CF DYSBIOSIS study AND
2. No chronic respiratory disease, excepting well-controlled asthma (such subjects may be prescribed inhaled bronchodilators of any class, and/ or inhaled corticosteroids provided it is in low-dose, no more than 500 mcg/ day beclomethasone dose-equivalent).
3. No antibiotic use (any class) in the prior 3 months.
4. Able to provide informed consent.
5. Willing and able to provide a stool sample and record a diet history.

Minimum age

18 Years

Maximum age

85 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

CF participants will be considered ineligible to participate if:
• Did not participate in the CF DYSBIOSIS study.
• Have a toxigenic producing strain of C. difficile.
• Unable to provide informed consent due to:
o Diminished understanding or comprehension.
• Evidence of active mucosal bowel disease
• Intolerance to high-fibre foods
• Any perceived contraindication to consumption of the test products.
• Additional antibiotic use in the last 1 month (above and beyond regular, baseline antibiotics and rotating nebulized antibiotics)
• Unwilling to provide consent.

Healthy Control participants will be considered ineligible to participate if:
• Did not participate in the CF DYSBIOSIS study.
• A chronic respiratory disease other than well-controlled asthma.
• Consumption of any antibiotic in the prior 3 months.
• Unable to provide informed consent due to:
o Diminished understanding or comprehension.
• Evidence of active mucosal bowel disease
• Intolerance to high-fibre foods
• Any perceived contraindication to consumption of the test products.
• Unwilling to provide consent.

Study design

Statistical methods / analysis

Comparison of the intervention both within subject and between a CF population and a Healthy population as assessed by the statistical difference between outcomes for each population.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

9/04/2018

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

20

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Mater Adult Hospital - South Brisbane

Recruitment postcode(s) [1]

4101 - South Brisbane

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Mater Misericordiae Ltd

Country [1]

Australia

Primary sponsor type

Hospital

Name

Mater Misericordiae Ltd

Country

Australia

Secondary sponsor category [1]

None

Name [1]

N/A

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Mater Misericordiae Human Ethics Committee

Ethics committee address [1]

Mater Research
Level 2 Aubigny place
Raymond Terrace
South Brisbane QLD 4101

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

04/12/2017

Approval date [1]

08/02/2018

Ethics approval number [1]

HREC/17/MHS/144

Summary

Brief summary

Cystic Fibrosis (CF) is associated with a significant increase in gut dysbiosis. Exposure to multiple courses of antibiotics as well as an inherently inflammatory gut contributes to this. We have shown that there are significant differences between the CF gut and healthy volunteers in these respects. High amylose maize starch (HAMS) is a pre-biotic food stuff produced in such a way as to encourage the production of beneficial, anti-inflammatory compounds. In laboratory culture, we have shown that HAMS increases the production of these compounds. What is not clear however is whether this laboratory data translates to a clinical benefit. This study will attempt to understand the impact of HAMS supplementation on the bacteria in the gut and the ability of the gut to make anti-inflammatory compounds, in adult patients with CF as well as in healthy control subjects.

Trial website

Public notes

Attachments [1]

/AnzctrAttachments/374471-CF HAMS PROTOCOL V1 JAN 2018 - CLEAN.docx (Protocol)

Contacts

Principal investigator

Name

Dr Lucy D Burr

Address

Respiratory Research Unit
Mater Research
Level 3 Aubigny Place
Raymond Terrace
South Brisbane QLD 4101

Country

Australia

Phone

+61731632128

Email

[email protected]

Contact person for public queries

Name

Megan L Martin

Address

Respiratory Research Unit
Mater Research
Level 3 Aubigny Place
Raymond Terrace
South Brisbane QLD 4101

Country

Australia

Phone

+61731632128

Email

[email protected]

Contact person for scientific queries

Name

Lucy Burr

Address

Respiratory Research Unit
Mater Research
Level 3 Aubigny Place
Raymond Terrace
South Brisbane QLD 4101

Country

Australia

Phone

+61731632128

Email

[email protected]

Trial Review

Documents added manually

Documents added automatically