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Trial registered on ANZCTR


Registration number
ACTRN12614000079640
Ethics application status
Approved
Date submitted
12/12/2013
Date registered
22/01/2014
Date last updated
6/03/2019
Date data sharing statement initially provided
6/03/2019
Date results information initially provided
6/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Fruit and vegetable supplement study in obese adults aged 50 years or older
Scientific title
Randomised Controlled Trial to examine the effects of a Fruit and Vegetable Supplement vs placebo on gene expression of inflammatory pathways, systemic inflammation, lipid metabolism, insulin resistance, CVD risk and plasma antioxidant levels, in obese adults aged 50 years or older
Secondary ID [1] 283648 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 290595 0
Condition category
Condition code
Inflammatory and Immune System 290982 290982 0 0
Normal development and function of the immune system
Diet and Nutrition 291308 291308 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
An 8-week double-blinded, parallel, placebo-controlled RCT to examine the effects of a fruit and vegetable supplement vs placebo (3 capsules twice daily with meals) on gene expression of inflammatory pathways, systemic inflammation, lipid metabolism, insulin resistance, CVD risk and plasma antioxidant levels, in obese adults aged 50 years or older.

Participants will be screened for study eligibility, including medical history, medication usage, blood pressure and blood chemistry. Blood samples will be obtained by venepuncture by trained personnel for determination of full blood count, liver function tests and electrolytes, urea, creatinine.

Once the screening blood test results have been received, eligible participants will be booked in and given advice on how to restrict fruit and vegetable intake to no more than three serves per day from two weeks prior to visit 1.

Visit 1: This is the study randomisation visit. Participants will arrive at the HMRI clinic after a 12-hour overnight fast. They will have a fasting venous blood sample collected, and their weight and waist circumference measured. Blood samples will be collected, and blood pressure and pulse wave velocity (arterial stiffness) will be recorded. Participants will complete quality of life, food frequency and 24-hour food recall questionnaires, and medication use and medical history will be checked. Body composition will be measured by full body dual-energy x-ray absorptiometry (DEXA). At the completion of this visit, participants will receive capsules: fruit and vegetable supplement, or placebo. Participants will be instructed to take 3 capsules twice daily with meals. Participants will be advised to continue their usual diet, noting that they will need to continue to restrict fruit and vegetable intake to no more than three serves each day for the study duration. Subjects who have a higher regular fruit and vegetable intake will receive advice on suitable substitutions, to assist them with adherence. Participants will also receive a pill diary to record supplements use daily for the 8 weeks.

Phone call 1, 2 and 3: During the intervention period, subjects will be telephoned fortnightly for motivational purposes, to collect information on compliance with the supplements and dietary restriction, and to establish whether any side effects have been experienced.

Visit 2: Visit 2 will be conducted eight weeks after visit 1. Participants will arrive at the HMRI clinic after a 12-hour overnight fast. They will have a fasting venous blood sample collected, and their weight and waist circumference measured. Blood pressure and pulse wave velocity (arterial stiffness) will be recorded. Body composition will be measured by a full body dual-energy x-ray absorptiometry (DEXA) scan. Participants will complete quality of life and 24-hour food recall questionnaires, and medication use and medical history will be checked. Participants will return any unused capsules and their completed pill diary, and will be instructed to resume their usual diet.

Investigational Product
The active supplement capsules used in this study contain mostly fruit and vegetable juice powder and pulp, resembling fine, brown, granular powder in an opaque gelatine capsule. The supplements are made from fruits, vegetables and other ingredients intended for human consumption, commonly consumed by humans for many years. The fruits and vegetables are cleaned, washed and chilled before juicing. The chilled juices are dried using a proprietary drying process.

Ingredients:
Fruit juice powder and pulp from: Acerola cherry, apple, artichoke, beet, bilberry, blackberry, black currant, blueberry, broccoli, cabbage, carrot, cocoa, concord grape, cranberry, date, elderberry, garlic, grape seed extract, green tea, kale, oat bran, orange, papaya, parsley, peach, pineapple, pomegranate, raspberry, red currant, rice bran, spinach, tomato.

Other ingredients: Gelatin, glucomannan, bromelain, calcium ascorbate, citrus pectin, beetroot powder, citrus bioflavonoids from tangerine, mixed tocoperhols, calcium carbonate, garlic powder, Spirulina pacifica, magnesium oxide, natural mixed carotenoids, natural enzyme blend, papain, sugar beet fibre, oat bran fibre, date fibre, prune fibre, rice bran, silicon dioxide, Lactobacillus acidophilus, vegetable derived magnesium stearate, folic acid.

Clinical Test Product Representative Nutritional Values, per 6 capsules daily dose
Nutrient
beta-carotene 3.4 mg/ 5835 IU
Vitamin E 2.8 mg/ 4 IU
Vitamin C 300mcg
Folate 200mcg
Intervention code [1] 288349 0
Treatment: Drugs
Comparator / control treatment
Placebo capsules: three capsules twice daily for 8 weeks.
The placebo capsules contain microcrystalline cellulose, dicalcium phosphate, magnesium stearate and FD&C yellow #6.
Control group
Placebo

Outcomes
Primary outcome [1] 290968 0
Gene expression of inflammatory pathways including NFKB, MAPK & AMPK.
Microarray analysis will be used in the discovery phase to identify pathways of interest.
Real-time PCR will be performed on genes which demonstrate the greatest fold difference in expressions up to a maximum of 10 genes.
Timepoint [1] 290968 0
Baseline versus week 8 (end of treatment)
Secondary outcome [1] 305697 0
Plasma cytokines (TNF-a, sTNFR1, sTNFR2, CRP, IL-10) and lipid metabolism/insulin resistance (cholesterol, triglycerides, LDL, HDL, HbA1c, oxidised LDL) will be analysed.
Cholesterol, triglycerides, LDL, HDL, HbA1c, oxidised LDL and CRP will measured by the Hunter Area Pathology Service.
TNF-a, sTNFR1, sTNFR2, CRP and IL-10 will be measured in our laboratory in plasma using commercial ELISA assay kits.
Timepoint [1] 305697 0
Baseline versus week 8 (end of treatment)
Secondary outcome [2] 305704 0
Arterial stiffness measured by pulse wave velocity using the
SphygmoCor Pulse Wave Velocity System SCOR-Vx (AtCor Medical, Sydney, Australia).
Timepoint [2] 305704 0
Baseline versus week 8 (end of treatment)
Secondary outcome [3] 305705 0
Serial Blood pressure measurements (mmHg) using an automatic sphygmomanometer (Welch Allyn 6000 Series).
Timepoint [3] 305705 0
Baseline versus week 8 (end of treatment)
Secondary outcome [4] 305706 0
Plasma antioxidant levels (alpha-carotene, beta-carotene, lutein, lycopene, beta-cryptoxanthin) will be analysed by reverse phase HPLC, using methods established in our laboratory
Timepoint [4] 305706 0
Baseline versus week 8 (end of treatment)

Eligibility
Key inclusion criteria
Males and females aged >=50 years; obese (BMI >=30kg/m2); absence / irregular menses in females; non-smokers.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unwilling or unable to limit intake of fruit and vegetables to no more than 3 serves per day; dietary or nutritional supplement use within the previous 4 weeks; current smokers; chronic excessive alcohol consumption; current participation in a weight management program or actively attempting to lose weight; current use of any medication known to significantly influence inflammation and allergy to fruit or vegetables.

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)
Computer-generated randomisation code held by an independent statistician. Allocation will be concealed from investigators, until each subject has entered the trial and received a randomisation code.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation.
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
Triple blinded.
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on our previous studies of expression of multiple genes involved in inflammatory pathways, we can calculate an appropriate sample size using RT-PCR confirmation of gene expression data. In order to have 80% power to detect a mean difference of 20%, with SD = 30%, we will need n=26 subjects per group. Allowing for 20% dropouts, we need to recruit 32 subjects per group, a total of n=64 participants.
Baseline data: (demographics, biomarkers, dietary intake) will be compared using the unpaired Student’s t test (parametric data) or Mann Whitney U test (non-parametric data).
Intervention results: Following the intervention, study outcomes will be analysed using analysis of covariance (ANCOVA) to test for differences between treatment groups after adjusting for baseline values.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/03/2014
Actual
2/04/2014
Date of last participant enrolment
Anticipated
Actual
15/10/2014
Date of last data collection
Anticipated
Actual
16/12/2014
Sample size
Target
64
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 288327 0
Commercial sector/Industry
Name [1] 288327 0
NSA, LLC
Country [1] 288327 0
United States of America
Primary sponsor type
University
Name
University of Newcastle
Address
University Drive, Callaghan, NSW, 2308.
Country
Australia
Secondary sponsor category [1] 287043 0
None
Name [1] 287043 0
Address [1] 287043 0
Country [1] 287043 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290220 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 290220 0
Hunter New England Research Ethics & Governance Unit
Locked Bag No 1
New Lambton NSW 2305
Ethics committee country [1] 290220 0
Australia
Date submitted for ethics approval [1] 290220 0
13/01/2014
Approval date [1] 290220 0
03/03/2014
Ethics approval number [1] 290220 0
14/02/19/3.01

Summary
Brief summary
This study will investigate the molecular mechanisms by which a fruit and vegetable supplement modulates systemic inflammation. Based on previous studies utilising fruit and vegetable supplements and our own fruit and vegetable withdrawal study, we hypothesise that the extract will modify systemic inflammatory pathways, including NF-kappaB, AMPK, MAPK, PPARalpha/gamma and TLR2/4, among others. In addition, various proteins associated with inflammation, lipid metabolism and insulin resistance will be improved. Determining whether the supplement is an effective treatment for reducing systemic inflammation in obesity and identifying the mechanisms involved may assist in reducing the risk of chronic diseases, including CVD and diabetes. This is critically important for reducing the burden of disease in this subgroup of the population for whom weight management/ weight loss has not been achievable.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44522 0
Prof Lisa Wood
Address 44522 0
Centre for Asthma and Respiratory Diseases
Level 2 West Wing, HMRI Building
Lot 1 Kookaburra Circuit
New Lambton Heights NSW 2305
Country 44522 0
Australia
Phone 44522 0
+61 2 4042 0147
Fax 44522 0
+61 2 4042 0046
Email 44522 0
[email protected]
Contact person for public queries
Name 44523 0
Lisa Wood
Address 44523 0
Centre for Asthma and Respiratory Diseases
Level 2 West Wing, HMRI Building
Lot 1 Kookaburra Circuit
New Lambton Heights NSW 2305
Country 44523 0
Australia
Phone 44523 0
+61 2 4042 0147
Fax 44523 0
+61 2 4042 0046
Email 44523 0
[email protected]
Contact person for scientific queries
Name 44524 0
Lisa Wood
Address 44524 0
Centre for Asthma and Respiratory Diseases
Level 2 West Wing, HMRI Building
Lot 1 Kookaburra Circuit
New Lambton Heights NSW 2305
Country 44524 0
Australia
Phone 44524 0
+61 2 4042 0147
Fax 44524 0
+61 2 4042 0046
Email 44524 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
There is no plan for IPD sharing for this trial


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Williams, E.; Baines, K.; Berthon, B.; Wood, L. Ef... [More Details]
Conference abstractNo Williams EJ, Baines KJ, Berthon BS, Wood LG. Effec... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffects of an encapsulated fruit and vegetable juice concentrate on obesity-induced systemic inflammation: A randomised controlled trial.2017https://dx.doi.org/10.3390/nu9020116
N.B. These documents automatically identified may not have been verified by the study sponsor.