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Trial registered on ANZCTR


Registration number
ACTRN12616000185460
Ethics application status
Approved
Date submitted
10/02/2016
Date registered
12/02/2016
Date last updated
3/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of Garlic on Gut microbiota, Inflammation & Cognition in hypertensives: The GarGIC trial
Scientific title
The effect of Kyolic aged garlic extract on gut microbiota, inflammation and cognition in hypertensive adults: a 3-month randomised placebo-controlled trial
Secondary ID [1] 288516 0
Nil
Universal Trial Number (UTN)
Trial acronym
GarGIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
hypertension 297589 0
Condition category
Condition code
Cardiovascular 297784 297784 0 0
Hypertension
Alternative and Complementary Medicine 297785 297785 0 0
Herbal remedies
Inflammatory and Immune System 297786 297786 0 0
Normal development and function of the immune system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Our study will comprise a double-blind parallel randomised placebo-controlled trial of 12 weeks duration investigating the effect of Kyolic aged garlic extract on gut microbiota, inflammatory markers, and cognitive function in patients with high blood pressure. The active treatment group will be allocated to two daily capsules of aged garlic extract (1.2 g Kyolic Reserve, 1.2 mg S-allylcysteine).

Compliance will be assessed by return of trial capsules, as well as diary entries.
Intervention code [1] 293879 0
Treatment: Other
Comparator / control treatment
The control group will be allocated to two daily placebo capsules (microcrystalline cellulose) matched in appearance and size to the active treatment capsules. Capsules will be packaged in identical opaque containers including a sachet of activated carbon to eliminate any odour.
Control group
Placebo

Outcomes
Primary outcome [1] 297312 0
Clinical blood pressure
A trained research assistant will use a validated and calibrated digital sphygmomanometer with appropriate sized cuffs. The display of the sphygmomanometer is to be positioned away from the patient to assure blinding to the BP readings. BP measurement to be taken with patient in seated position with arm supported at heart level, after 5 min rest, after abstinence from food, nutritional supplements, caffeinated beverages, and smoking for a minimum of 2 hours prior to BP measurement at approximately the same time/day of the week. BP will be recorded as three serial measurements at intervals of 30 seconds. The mean of the three BP measurements will be used in the analysis.
Timepoint [1] 297312 0
12 weeks compared to baseline
Primary outcome [2] 297313 0
Stool test
Enrolled patients will be provided with a test kit from Genova (www.gtx.com, USA) via Nutripath, Melbourne, Australia at their first appointment for baseline testing, and will be instructed to collect a stool sample as close as possible to their baseline appointment and sent the kit to Genova for a Microbial Ecological Profile (GI Effects Stool Profile), providing a comprehensive profile of commensal bacterial species in colony-forming-units (CFU)/g stool by PCR-DNA analysis. PCR-DNA analysis offers a more accurate result than standard culturing technologies. The report will be used to calculate Chaos diversity, Shannon diversity index, and Firmicute/Bacteroides ratio and relevant correlations.
Timepoint [2] 297313 0
12 weeks compared to baseline
Primary outcome [3] 297314 0
Central hemodynamic measures
Pulse Wave velocity (PWV)is a strong predictor of cardiovascular morbidity, and is most reliably measured by a comparison of carotid to femoral pulse wave. The SphygmoCor Xcel device (Atcor Medical) provides the gold standard validated instrument.
Timepoint [3] 297314 0
12 weeks compared to baseline
Secondary outcome [1] 320693 0
Inflammatory markers
The research assistant, trained in phlebotomy, will take a fasted blood sample for testing of inflammatory markers TNF-alpha and interleukin-6 or interleukin-10.
Timepoint [1] 320693 0
12 weeks compared to baseline
Secondary outcome [2] 320694 0
Cognitive function testing
Patients will undergo the Swinburne University Computerised Cognitive Assessment Battery (SUCCAB) test in the NIIM cognitive function labs. The SUCCAB test consists of eight computer-based tasks assessing speed and accuracy, shown to correlate to cognitive decline through ageing, with a difference in 60 milliseconds in speed correlating to about 10 years of ageing.
Our research team has been collaborating closely with the ‘inventor’ of the computerised test in a number of projects, and NIIM has recently built the laboratory facilities to undertake the testing in a controlled environment.
Testing takes about 30 minutes including a practice session of about 10 minutes for the participant to familiarise themselves with the equipment and the task battery.
Timepoint [2] 320694 0
12 weeks compared to baseline

Eligibility
Key inclusion criteria
Inclusion criteria
- Essential hypertension: Mean systolic SBP >=140 mm Hg or diastolic blood pressure >=90 mm Hg to be confirmed under trial conditions at the screening appointment (at screening mean DBP of >=88 / SBP >=135 mm Hg will be included)
- Either not on blood pressure medication, or on established plan of blood pressure medication (one or more classes) for at least 2 months
- The patient’s doctor is not planning to change current treatment during the 3 month trial
- Able to give informed consent
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria
- Poor comprehension of written or spoken English
- Current or previous antibiotic treatment within the last 2 months of study enrolment
- Currently taking anti-inflammatory agents, glucocorticoids or other immune regulating prescription medication
- Currently taking probiotics
- Currently taking garlic supplements
- History of intestinal surgery, inflammatory bowel disease, celiac disease, lactose intolerance, chronic pancreatitis, or diagnosed malabsorption disorder
- Planning surgery in the next 3-4 months
- Unstable other medical conditions or serious illness, at the discretion of the GP, e.g. dementia, terminal illness, recent bereavement, secondary hypertension, recent significant medical diagnosis, and pregnancy
- Severe hypertension (mean sitting SBP>=180 mm Hg and DBP >=110 mm Hg) at enrolment or subsequent visits during the study. Patients with severe hypertension will be referred back to their doctor for further management

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)
Active and placebo capsules will be packaged offsite in identical opaque containers containing each a sachet with activated carbon to remove the garlic smell. Patients, as well as investigators and research assistants will be blinded to the group allocation. Blinding success of patients will be evaluated at the end of the trial by questionnaire.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated permuted block randomisation schedule will be used to allocate patients to garlic or placebo groups within each recruitment site. The randomisation schedule will be generated by an independent researcher not involved in patient recruitment, patient care, data collection, and follow-up.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
STATISTICAL ANALYSIS
Primary outcome measures are blood pressure change over time (SBP/DBP); and gut microbiota change measured by microbial richness and diversity (Chao richness, Shannon diversity, F/B ratio).
Secondary outcomes are gut microbiota change as Firmicute/Bacteroides ratio (F/B ratio adults/elderly (n=21/20): ratio 12.5/2.5);22 changes in inflammatory markers TNF-alpha (garlic/placebo n=31/27: change 203 fg/ml, p=0.05)3 and IL-6 or IL-10; and changes in cognitive function assessed by the SUCCAB test.

Analyses
Continuous variables will be analysed by student t-test and analysis-of-covariance (ANCOVA), and categorical variables will be analysed by Chi-square test.
Subgroup analyses will be undertaken in responders (BP change in the garlic group) and non-responders (no significant BP change).
Correlations between BP change and gut microbiota change, inflammatory marker change or cognition change, will be analysed using Pearson correlation model.

Sample size
A sample size of 50 patients was calculated based on the following assumptions:
a) To detect a difference of 8 mmHg BP (SD=9) in BP change between the active treatment (n=25) and control (n=25) with 80% power and 95% confidence; b) to account for 10% drop-out or non-attendance at all appointments.
b) To detect a difference of 400 points in Chao richness in the garlic group compared to placebo at 3 months compared to placebo with 80% power and 95% confidence (n=17 hypertensives/10 control , p=0.05).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/03/2016
Actual
31/03/2016
Date of last participant enrolment
Anticipated
30/09/2016
Actual
30/09/2016
Date of last data collection
Anticipated
Actual
31/01/2017
Sample size
Target
50
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 12719 0
3122 - Hawthorn
Recruitment postcode(s) [2] 12720 0
3123 - Hawthorn East
Recruitment postcode(s) [3] 12721 0
3124 - Camberwell

Funding & Sponsors
Funding source category [1] 292862 0
Commercial sector/Industry
Name [1] 292862 0
Wakunaga of America Co Ltd
Country [1] 292862 0
United States of America
Primary sponsor type
Individual
Name
A/Prof Dr Karin Ried
Address
National Institute of Integrative Medicine
21 Burwood Rd
Hawthorn, VIC 3122
Country
Australia
Secondary sponsor category [1] 291608 0
None
Name [1] 291608 0
nil
Address [1] 291608 0
n/a
Country [1] 291608 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294363 0
National Institute of Integrative Medicine Human Research Ethics Committee
Ethics committee address [1] 294363 0
Ethics committee country [1] 294363 0
Australia
Date submitted for ethics approval [1] 294363 0
09/02/2016
Approval date [1] 294363 0
16/02/2016
Ethics approval number [1] 294363 0
0029N_2016

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63442 0
A/Prof Karin Ried
Address 63442 0
National Institute of Integrative Medicine
21 Burwood Rd
Hawthorn, VIC 3122
Country 63442 0
Australia
Phone 63442 0
+61 3 9912 9545
Fax 63442 0
Email 63442 0
karinried@niim.com.au
Contact person for public queries
Name 63443 0
Karin Ried
Address 63443 0
National Institute of Integrative Medicine
21 Burwood Rd
Hawthorn, VIC 3122
Country 63443 0
Australia
Phone 63443 0
+61 3 9912 9545
Fax 63443 0
Email 63443 0
karinried@niim.com.au
Contact person for scientific queries
Name 63444 0
Karin Ried
Address 63444 0
National Institute of Integrative Medicine
21 Burwood Rd
Hawthorn, VIC 3122
Country 63444 0
Australia
Phone 63444 0
+61 3 9912 9545
Fax 63444 0
Email 63444 0
karinried@niim.com.au

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

Documents added manually
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