Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001561875
Ethics application status
Approved
Date submitted
4/10/2021
Date registered
17/11/2021
Date last updated
18/10/2022
Date data sharing statement initially provided
17/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of a formulation containing blackcurrant powder, L-theanine and pine bark extract on immune responses to influenza vaccine in older healthy adults
Scientific title
Effect of a formulation containing blackcurrant powder, L-theanine and pine bark extract on immune responses to influenza vaccine in older healthy adults
A multi-centred, randomised, double blind, placebo controlled, parallel study
Secondary ID [1] 305456 0
None
Universal Trial Number (UTN)
U1111-1269-7833
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Immune response to influenza vaccine 323835 0
Older age 323836 0
Condition category
Condition code
Infection 321343 321343 0 0
Other infectious diseases
Inflammatory and Immune System 321614 321614 0 0
Normal development and function of the immune system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Freeze-dried blackcurrants (with a minimum serve of 3.2 mg/kg anthocyanin) with 150 mg L-theanine and 150 mg pine bark extract added. The formulations will be a powder which will be mixed with 250 ml water and will be given daily for 12 weeks. Participants will be asked to fill out a short daily health questionnaire during the intervention period asking if the intervention has been consumed, which will serve as a reminder to take their intervention. In addition a weekly SMS/E-mail reminder will be sent. A one-week wash-out period will precede the intervention stage, where participants will be asked to avoid high-polyphenolic contain foods, such as excessive caffeine or chocolate. A SMS/E-mail reminder will be sent and a 3-day diet record will be taken during this week to assess baseline diet. After 4 weeks of intervention participants will be vaccinated with the influenza vaccine developed according to World Health Organisation (WHO) guidelines for 2022 and approved by Medsafe, New Zealand. Vaccines will be administered intramuscularly in the deltoid region of the arm by a qualified nurse (Life Care Consultants, New Zealand) as part of this study.
Intervention code [1] 321854 0
Treatment: Other
Comparator / control treatment
A placebo powder is used as a control and will be weight matched to the active intervention and served with 250 ml water. The control contains no known bioactive ingredients and is matched for appearance, texture and flavour. The placebo powder is commercially supplied by Sensient Technologies and contains a base of citrus fibre, maltodextrin and sugar. The placebo powder will be given daily for 12 weeks. Participants will be asked to fill out a short daily health questionnaire during the intervention period asking if the intervention has been consumed, which will serve as a reminder to take their intervention. In addition a weekly SMS/E-mail reminder will be sent. Participants assigned to the placebo intervention will be subject to the same trial activities as the active intervention. Such as, a one-week wash-out period will precede the intervention stage, where participants will be asked to avoid high-polyphenolic contain foods, such as excessive caffeine or chocolate. A SMS/E-mail reminder will be sent and a 3-day diet record will be taken during this week to assess baseline diet. After 4 weeks of intervention participants will be vaccinated with the influenza vaccine developed according to World Health Organisation (WHO) guidelines for 2022 and approved by Medsafe, New Zealand. Vaccines will be administered intramuscularly in the deltoid region of the arm by a qualified nurse (Life Care Consultants, New Zealand) as part of this study.
Control group
Placebo

Outcomes
Primary outcome [1] 329127 0
Specific T-cell subset proliferation of ex-vivo stimulated peripheral immune cells isolated from participants peripheral blood with influenza antigens.
Timepoint [1] 329127 0
0, 6, 8 (primary timepoint) and 12 weeks post initiation of intervention.
Primary outcome [2] 329379 0
Cytokine production of ex-vivo stimulated peripheral immune cells isolated from participants peripheral blood with influenza antigens.
Timepoint [2] 329379 0
0, 6, 8 (primary timepoint) and 12 weeks post initiation of intervention.
Secondary outcome [1] 401554 0
Antigen specific immune response to the influenza vaccination as assessed by vaccine antigen-specific plasma IgG1 concentration.
Timepoint [1] 401554 0
0, 6, 8 and 12 weeks post initiation of intervention.
Secondary outcome [2] 401555 0
Antigen specific immune response to the influenza vaccination assessed by vaccine antigen-specific haemagglutination inhibition (HAI) in blood.
Timepoint [2] 401555 0
0, 6, 8 and 12 weeks post initiation of intervention.
Secondary outcome [3] 401556 0
Incidence of upper respiratory tract infection (URTI) to measure common illness and/or symptoms (e.g. coughs and colds) using the validated Wisconsin Upper Respiratory Symptom Survey – (WURSS-24).
Timepoint [3] 401556 0
Daily over the 12 week intervention period.
Secondary outcome [4] 401558 0
Innate immune cell populations in participants peripheral blood such as plasma cells expressing IgM and IgG1, natural killer (NK) cells, monocytes, dendritic cells, macrophages, T cells including subsets cytotoxic T cells, T helper cells, NKT cells and regulatory T cells . In addition the expression of activation markers relevant to each population will be calculated. This is an exploratory outcome.
Timepoint [4] 401558 0
0, 6, 8 and 12 weeks post initiation of intervention.
Secondary outcome [5] 401559 0
Plasma vitamin C concentrations.
Timepoint [5] 401559 0
0, 6, 8 and 12 weeks post initiation of intervention.
Secondary outcome [6] 401560 0
Plasma primary and secondary metabolites. This is an exploratory outcome and metabolites that significantly change between placebo and active treatments will be the focus of this outcome.
Timepoint [6] 401560 0
0, 6, 8 and 12 weeks post initiation of intervention.
Secondary outcome [7] 402387 0
Antigen specific immune response to the influenza vaccination as assessed by vaccine antigen-specific plasma IgG3 concentration.
Timepoint [7] 402387 0
0, 6, 8 and 12 weeks post initiation of intervention.

Eligibility
Key inclusion criteria
Age: Aged over 50 years
Sex: Any gender
Body weight <120Kg
Health: Healthy as gauged by self-assessment and result on the General Health Questionnaire.
Blood parameters which do not indicate clinically significant illness for albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea, calcium, chloride, creatinine, potassium, sodium, total bilirubin, total protein, glucose and HBA1c. .
Agreement: Participant having given written informed consent to comply with the conditions of the trial.
No allergies to ingredients contained in the active or placebo treatment or the influenza vaccine, such as blackcurrant or egg products.
No previous severe reaction to the influenza vaccine
Did not receive the influenza vaccine in 2021 and are willing to have the influenza vaccine as part of this study.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Blood parameters for albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea, calcium, chloride, creatinine, potassium, sodium, total bilirubin, total protein, glucose and HBA1c being indicative of clinically significant illness.
Non-fasting: Having consumed anything apart from water in the twelve hours prior to blood tests.
Allergic or intolerant blackcurrant or other ingredients containing in the active or placebo treatments or egg products (potentially in the influenza vaccine).
Had a previous severe reaction to the influenza vaccine.
Had the influenza vaccine in 2021.
Pregnant or breastfeeding or planning to get pregnant in the near future.
Long term chronic illnesses requiring treatment, such as cancer and cardiovascular disease.
Participants will be excluded if they are unwilling or unable to provide informed consent or comply with the study procedures.
Participants that have Type I or II diabetes (ii) blood borne diseases (e.g. hepatitis), (iii) clinically diagnosed high/low blood pressure, (iv) are taking medication that affects the properties of blood (e.g. blood clotting).

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)
Central randomisation via a computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computerised sequence generation.
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
Power calculation to justify our population size on our primary outcome (proliferation of specific T-cell subset following ex vivo stimulation with influenza antigens) were based on data from Ivory et al. (2017) with a study population aged between 50-64 years. The population size of the proposed study design is also appropriately powered for secondary immune measures based on changes in seroconversion eight weeks post-vaccination by Nishihira et al. (2017), and increased antigen specific IgG1 and IgG3 four weeks post-vaccination (Rizzardini et al. 2012). Altogether, our suggested group size of 55 is in similar range to these to investigating both adaptive and humoral immunity as primary outcomes using a vaccination model. We will aim to enroll 120 participants onto the study to account for people dropping out of the study.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
17/01/2022
Actual
7/02/2022
Date of last participant enrolment
Anticipated
14/04/2023
Actual
Date of last data collection
Anticipated
14/07/2023
Actual
Sample size
Target
120
Accrual to date
68
Final
Recruitment outside Australia
Country [1] 24157 0
New Zealand
State/province [1] 24157 0
Manawatu-Wanganui and Auckland

Funding & Sponsors
Funding source category [1] 309811 0
Government body
Name [1] 309811 0
The University of Auckland (in its capacity as Challenge Contractor for High Value Nutrition National Science Challenge fund)
Country [1] 309811 0
New Zealand
Primary sponsor type
Government body
Name
The New Zealand Institute for Plant and Food Research
Address
Private Bag 11600
Palmerston North 4442
Country
New Zealand
Secondary sponsor category [1] 310845 0
Commercial sector/Industry
Name [1] 310845 0
AlphaGen NZ Ltd
Address [1] 310845 0
376 Great North Road,
Grey Lynn
Auckland
1021
Country [1] 310845 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309558 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 309558 0
Ethics committee country [1] 309558 0
New Zealand
Date submitted for ethics approval [1] 309558 0
29/10/2021
Approval date [1] 309558 0
15/11/2021
Ethics approval number [1] 309558 0
2021 EXP 11357

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

Contacts
Principal investigator
Name 114582 0
Dr Kerry Bentley-Hewitt
Address 114582 0
The New Zealand Institute for Plant & Food Research
Private Bag 11600
Palmerston North 4442
Country 114582 0
New Zealand
Phone 114582 0
+64 6 3556215
Fax 114582 0
Email 114582 0
[email protected]
Contact person for public queries
Name 114583 0
Kerry Bentley-Hewitt
Address 114583 0
The New Zealand Institute for Plant & Food Research
Private Bag 11600
Palmerston North 4442
Country 114583 0
New Zealand
Phone 114583 0
+64 6 3556215
Fax 114583 0
Email 114583 0
[email protected]
Contact person for scientific queries
Name 114584 0
Kerry Bentley-Hewitt
Address 114584 0
The New Zealand Institute for Plant & Food Research
Private Bag 11600
Palmerston North 4442
Country 114584 0
New Zealand
Phone 114584 0
+64 6 3556215
Fax 114584 0
Email 114584 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
Means and standard errors of combined participant data will be published only.


What supporting documents are/will be available?

No Supporting Document Provided



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.