Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001511820
Ethics application status
Approved
Date submitted
9/08/2021
Date registered
5/11/2021
Date last updated
31/05/2024
Date data sharing statement initially provided
5/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Lactoferrin Supplementation, Immune Function & Respiratory Virus Infection in healthy, older adults: The LIFE Trial
Scientific title
A randomised, double blinded, placebo controlled trial assessing the effect of bovine lactoferrin supplementation on immune cell profiles, ex-vivo response to respiratory virus Infection and systemic inflammation in healthy, older adults.
Secondary ID [1] 304912 0
None
Universal Trial Number (UTN)
U1111-1268-3042
Trial acronym
LIFE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Immune function 323050 0
Respiratory virus infection 323051 0
Inflammation 323052 0
Condition category
Condition code
Inflammatory and Immune System 320620 320620 0 0
Normal development and function of the immune system
Infection 321307 321307 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised, double-blind, placebo-controlled, 4-week intervention trial, with 3 arms in parallel. The trial is testing a bovine lactoferrin supplement, with healthy, older adults randomly assigned to either high or low dose bovine lactoferrin or placebo for 4 weeks.

Bovine lactoferrin is a protein found in cow’s milk which has been shown to modulate the immune system and reduce systemic inflammation. This trial will assess the efficacy of both high dose and low dose bovine lactoferrin supplementation in improving immune function, by measuring cytokine release from virus-infected peripheral blood mononuclear cells (PBMCs). The effect of bovine lactoferrin on peripheral immune cell profiles and systemic inflammation will also be examined.

All participants will be randomised at the baseline visit, to receive a 4-week intervention with either:
Arm 1: High dose bovine lactoferrin 600mg/d capsule
or
Arm 2: Low dose bovine lactoferrin 200mg/d capsule
or
Arm 3: Placebo control (Microcrystalline cellulose) capsule

Participants will be instructed to consume 1 capsule per day with water, in the morning, before food. For the duration of the trial, participants will complete a trial diary entry each day to record compliance with the intervention, any illnesses, and adverse effects.

The trial will be conducted at the Hunter Medical Research Institute, by the University of Newcastle. Participants will attend the Clinical Trials Facility on Level 4 at the Hunter Medical Research Institute (HMRI) for a 1 hour visit, after a 12-hour overnight fast before and after the 4 week intervention, for a total of two trial visits. Height, body weight and blood pressure will be measured. A venous blood sample will be collected via venepuncture by trained personnel. Medical history and medication use will be recorded. Participants will also be asked to complete a food frequency questionnaire to assess usual dietary intake, and a 24-hour food recall with frequency checklist will be collected to assess recent dietary intake. Participants will also complete a health-related quality of life questionnaire (HRQOL-14). Participants will be contacted by telephone at week 2 for motivational purposes, to collect information on compliance with the intervention and to establish whether any adverse events or illness have been experienced. The telephone call will be approximately 15 minutes in duration.

Compliance with the intervention will be monitored and assessed using the trial diary and pill countback of remaining trial supplement capsules at V2. Participants will be asked to complete the diary each day by recording consumption of the trial supplement.
Intervention code [1] 321307 0
Treatment: Drugs
Intervention code [2] 321825 0
Prevention
Comparator / control treatment
Placebo control (Microcrystalline cellulose) capsule 1/d
Control group
Placebo

Outcomes
Primary outcome [1] 328439 0
Ex-vivo production of Interferon-gamma by virus-infected PBMCs
Timepoint [1] 328439 0
4 weeks post initiation of treatment,
Secondary outcome [1] 399014 0
Ex-vivo production of IL-6 by virus-infected PBMCs
Timepoint [1] 399014 0
4 weeks post initiation of treatment
Secondary outcome [2] 399015 0
Peripheral blood immune cell analysis of immune cell subset numbers and percentages
Timepoint [2] 399015 0
4 weeks post initiation of treatment
Secondary outcome [3] 399016 0
Plasma IL-6
Timepoint [3] 399016 0
4 weeks post initiation of treatment
Secondary outcome [4] 401402 0
Ex-vivo production of interferon-lambda by virus-infected PBMCs
Timepoint [4] 401402 0
4 weeks post initiation of treatment
Secondary outcome [5] 401405 0
Plasma CRP
Timepoint [5] 401405 0
4 weeks post initiation of treatment
Secondary outcome [6] 401406 0
Plasma TNF-a
Timepoint [6] 401406 0
4 weeks post initiation of treatment
Secondary outcome [7] 402676 0
ex-vivo production of TNF-a by virus-infected PBMCs
Timepoint [7] 402676 0
4 weeks post initiation of treatment

Eligibility
Key inclusion criteria
• Males and females aged 50 years of age or older
• Non-smokers (ceased smoking more than 6 months prior)
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Cow’s milk allergy (self-reported)
• Dietary or nutritional supplement use within the previous 4 weeks. If appropriate to do so, supplements that are not being taken for a health condition may be washed out for 2-4 weeks before commencing the trial
• Current smokers (smoked within previous 6 months)
• Maintenance use of systemic corticosteroid, immunosuppressive or antibiotic drugs
• Unstable cardiac, renal, hypertensive, pulmonary, endocrine, immunologic, neurologic disorders
• Acute or terminal illness, human immunodeficiency virus (HIV) or active cancer
• Any other medical condition which may interfere with the participant’s ability to participate in the intervention.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All subjects will be given a unique study number. After eligibility is confirmed at the baseline visit, subjects will be allocated with a randomisation number in sequential order (according to age and gender strata) by an independent researcher. The randomisation number will correspond with the labelled trial supplement, packaged in opaque bottles, Trial supplements will be packaged and labelled by an external manufacturer, using the randomisation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation sequence will be determined by an independent statistician using computer generated codes. Randomisation will be stratified by age and gender, with variable block sizes. The statistician will send the randomisation schedule to the manufacturer.
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
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on our previous studies, we can expect interfeon-gamma release from stimulated PBMCs to decrease by 0.8SD following supplementation. We would need n=31 subjects per group to detect this difference (80% power, a=0.025). Allowing for 10% dropouts, we would require n=34 subjects per group, total n=102.
Data will be analysed using STATA 15 (StataCorp, Texas, USA). Normality will be assessed using Shapiro-Wilk tests. Baseline comparisons will be performed using independent t tests or Wilcoxon Rank Sum tests and Chi2 tests as appropriate. For primary and secondary outcomes both intention to treat (ITT) (using all available data) and per protocol (PPA) analyses will be conducted. Linear mixed effects models (LMM) will be used to determine the group difference in change from baseline during the intervention, for continuous variables. LMM will be fit by restricted maximum likelihood, with group and time as fixed effects, time as a random effect and adjusted as necessary for any baseline differences. Changes within each treatment compared to baseline will be examined using paired Student’s t test (normally distributed data) or Wilcoxon matched-pairs signed-rank tests (non-normally distributed data). Associations between continuous variables will be assessed using either Pearson’s or Spearman’s rank correlations. Significance will be accepted if p<0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/11/2021
Actual
3/08/2022
Date of last participant enrolment
Anticipated
1/07/2022
Actual
19/09/2023
Date of last data collection
Anticipated
29/07/2022
Actual
17/10/2023
Sample size
Target
102
Accrual to date
Final
103
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20097 0
Hunter Medical Research Institute - New Lambton Heights
Recruitment postcode(s) [1] 34805 0
2305 - New Lambton Heights

Funding & Sponsors
Funding source category [1] 309288 0
Government body
Name [1] 309288 0
Commonwealth of Australia, Department of Industry, Innovation and Science
Country [1] 309288 0
Australia
Funding source category [2] 309289 0
Commercial sector/Industry
Name [2] 309289 0
Noumi Limited
Country [2] 309289 0
Australia
Primary sponsor type
University
Name
The University of Newcastle
Address
University Drive, Callaghan, NSW, 2308.
Country
Australia
Secondary sponsor category [1] 310259 0
None
Name [1] 310259 0
None
Address [1] 310259 0
None
Country [1] 310259 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309123 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 309123 0
Ethics committee country [1] 309123 0
Australia
Date submitted for ethics approval [1] 309123 0
27/07/2021
Approval date [1] 309123 0
17/09/2021
Ethics approval number [1] 309123 0
2021/ETH10928

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

Contacts
Principal investigator
Name 113058 0
Prof Lisa Wood
Address 113058 0
Room 606, Medical Sciences Building
University of Newcastle
University Drive, Callaghan, NSW, 2308
Country 113058 0
Australia
Phone 113058 0
+61 2 49217485
Fax 113058 0
+61 2 49217903
Email 113058 0
[email protected]
Contact person for public queries
Name 113059 0
Bronwyn Berthon
Address 113059 0
The University of Newcastle
Level 2, West Wing, Hunter Medical Research Institute
C/- University Drive, Callaghan NSW 2308
Country 113059 0
Australia
Phone 113059 0
+61 2 4042 0116
Fax 113059 0
+61 2 4042 0046
Email 113059 0
[email protected]
Contact person for scientific queries
Name 113060 0
Bronwyn Berthon
Address 113060 0
The University of Newcastle
Level 2, West Wing, Hunter Medical Research Institute
C/- University Drive, Callaghan NSW 2308
Country 113060 0
Australia
Phone 113060 0
+61 2 4042 0116
Fax 113060 0
+61 2 4042 0046
Email 113060 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 IPD sharing plan for this trial, as there is no ethics approval for IPD sharing.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12717Informed consent form https://hmri.org.au/participate-research/life-trial[email protected] 382500-(Uploaded-27-05-2024-12-23-27)-LIFE PICF V3_28.04.22.pdf



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.