Trial Review

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Trial registered on ANZCTR


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] 294004 0
None
Universal Trial Number (UTN)
Trial acronym
CF HAMS STUDY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 306517 0
Condition category
Condition code
Respiratory 305625 305625 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 305650 305650 0 0
Cystic fibrosis
Oral and Gastrointestinal 305651 305651 0 0
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] 300275 0
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] 304737 0
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] 304737 0
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] 304763 0
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] 304763 0
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] 342985 0
Secondary outcomes include tolerability of supplementation, as assessed by GI symptoms questionnaires including the CFQ-R and the PROMIS questionnaires.
Timepoint [1] 342985 0
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] 343037 0
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] 343037 0
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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
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] 9995 0
Mater Adult Hospital - South Brisbane
Recruitment postcode(s) [1] 18834 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 298630 0
Hospital
Name [1] 298630 0
Mater Misericordiae Ltd
Country [1] 298630 0
Australia
Primary sponsor type
Hospital
Name
Mater Misericordiae Ltd
Address
Respiratory Research Unit
Mater Research
Level 3 Aubigny Place
Raymond Terrace, South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 297795 0
None
Name [1] 297795 0
N/A
Address [1] 297795 0
N/A
Country [1] 297795 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299589 0
Mater Misericordiae Human Ethics Committee
Ethics committee address [1] 299589 0
Mater Research
Level 2 Aubigny place
Raymond Terrace
South Brisbane QLD 4101
Ethics committee country [1] 299589 0
Australia
Date submitted for ethics approval [1] 299589 0
04/12/2017
Approval date [1] 299589 0
08/02/2018
Ethics approval number [1] 299589 0
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
Trial related presentations / publications
Public notes
Attachments [1] 2424 2424 0 0
/AnzctrAttachments/374471-CF HAMS PROTOCOL V1 JAN 2018 - CLEAN.docx (Protocol)

Contacts
Principal investigator
Name 80942 0
Dr Lucy D Burr
Address 80942 0
Respiratory Research Unit
Mater Research
Level 3 Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Country 80942 0
Australia
Phone 80942 0
+61731632128
Fax 80942 0
+61731638519
Email 80942 0
[email protected]
Contact person for public queries
Name 80943 0
Ms Megan L Martin
Address 80943 0
Respiratory Research Unit
Mater Research
Level 3 Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Country 80943 0
Australia
Phone 80943 0
+61731632128
Fax 80943 0
+61731638519
Email 80943 0
[email protected]
Contact person for scientific queries
Name 80944 0
Dr Lucy Burr
Address 80944 0
Respiratory Research Unit
Mater Research
Level 3 Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Country 80944 0
Australia
Phone 80944 0
+61731632128
Fax 80944 0
Email 80944 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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