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Trial registered on ANZCTR


Registration number
ACTRN12617000731392
Ethics application status
Approved
Date submitted
25/04/2017
Date registered
19/05/2017
Date last updated
26/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of a dietary ketone on immunity and tolerability in recreationally active, healthy males at rest.
Scientific title
The effect of 1,3-butanediol on immunity and tolerability in recreationally active, healthy males at rest.
Secondary ID [1] 291773 0
Nil
Universal Trial Number (UTN)
U111-1192-4543
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Exercise-Induced immunosuppression 302997 0
Gastrointestinal distress 302998 0
Systemic symptoms (e.g. dizziness, nausea) 303278 0
Condition category
Condition code
Inflammatory and Immune System 302460 302460 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 302461 302461 0 0
Normal oral and gastrointestinal development and function
Other 302707 302707 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental procedure: Participants will arrive at the laboratory at 06:00 h having fasted from 23:00 h the previous day and having abstained from caffeine, alcohol and strenuous exercise for the previous 24 h. Upon arrival, participants will have a cannula inserted into their antecubital vein and will rest quietly for ~10 min prior to initial blood and saliva samples, ketone levels and tolerability scores being collected (baseline measures). Participants will be asked to void their bladder before their body mass (shorts only), height and sum of 8 skinfolds are measured by an International Society for the Advancement of Kinanthropometry Level 1 Accredited Anthropometrist. To standardise nutritional status, participants will complete a 24-hour food diary the day before the trial and will be asked to follow this during the 24-hour prior to the second, third and fourth trials.

Participants will then consume a 200 ml citrus flavoured drink at two time points; 06:30 and 08:00 h. The drinks will be formulated to provide a series of different doses of 1,3-butanediol (1,3-BD); a) 0g/kg and 0g/kg; b) 0.5g/kg and 0g/kg; c) 0.7g/kg and 0g/kg and; d) 0.35 g/kg and 0.35 g/kg. Participants will be blinded to the dose of 1,3-BD in a randomised crossover design. Blood and saliva samples will be collected at 30, 120, 150 and 210 min spot the initial intake of 1,3-BD. Ketone levels will be measured at 15, 30, 45, 60, 75, 90 120, 150 and 210 min post the initial intake of 1,3-BD . Tolerability scores will be collected 30, 150, 210 and 480 min post the initial intake of 1,3-BD. Participants will be asked to describe additional symptoms experienced that were not specified on the questionnaire. Participants will be asked to identify what drink they consumed.

Participants will be unable to consume food or beverages throughout the duration of the trial (i.e. 06:00 h to ~10.00 h), however, water can be consumed ad libitum. 10 min prior to each saliva collection, participants will be asked to refrain from drinking. Participants will remain in the Sport Research Institute of New Zealand (SPRINZ) laboratory, where they will remain resting. All samples will be collected and tolerability questionnaires will be completed in the SPRINZ laboratory. Following completion, participants will be provided with 400 ml of a carbohydrate drink and recommended to return to their normal dietary patterns and asked to return to the laboratory after 3 – 10 days for each subsequent trial.

Drink formulation: Citrus flavoured drinks will be made using Food Chemicals Codex (FCC) approved, food grade 1,3-BD (Product Number 02-59620; Penta Manufacturing Ltd, Livingston, USA).

Safety monitoring: Participant tolerability, side-effects and abnormal haematological values will be immediately reported to a medical doctor. This study will be immediately terminated when advised the medical doctor or following intractable symptoms after 1,3-BD consumption in 2 trial arms (i.e. 10% of trials). Participants will be followed up 3 days and 1 week after the consumption of 1,3-BD to ascertain if any adverse effects occurred. Participants will also be encouraged to report any symptoms following consumption of 1,3-BD by email, phone or text.
Intervention code [1] 297882 0
Prevention
Intervention code [2] 298061 0
Treatment: Other
Comparator / control treatment
200ml citrus flavoured drink containing no 1,3-butanediol. All drinks will aim to be taste matched
Control group
Placebo

Outcomes
Primary outcome [1] 301876 0
T-cell mediated immune response (i.e. peripheral blood T-cell subset count and balance, and stimulated cytokine production) using the Muse, RT-PCR, Magpix. T-cells will be stimulated using Staphylococcal enterotoxin B within a whole blood culture.
Timepoint [1] 301876 0
Within 30 minutes before and 30, 150 and 210 minutes after consumption of 1,3-butanediol.
Primary outcome [2] 301878 0
Salivary flow rate (i.e. volume of unstimulated saliva drool collected divided by collection time)
Timepoint [2] 301878 0
Within 30 minutes before and 30, 150 and 210 minutes after consumption of 1,3-butanediol.
Primary outcome [3] 302162 0
Salivary immunoglobulin A secretion rate (i.e. amount of salivary immunoglobulin A collected divided by collection time). sIgA will be measured an using in-house ELISA method.
Timepoint [3] 302162 0
Within 30 minutes before and 30, 150 and 210 minutes after consumption of 1,3-butanediol.
Secondary outcome [1] 334171 0
Gastrointestinal distress / symptoms as measured using a questionnaire previously used in the study 'The effect of carbohydrate gels on gastrointestinal tolerance during a 16-km run' by Pfeiffer and colleagues. Additional symptoms were added to the questionnaire as described within "Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects" by Clarke and colleagues. Participants will be prompted for additional symptoms following the completion of each form.
Timepoint [1] 334171 0
Within 30 minutes before and 30, 150 and 210 minutes after consumption of 1,3-butanediol.
Secondary outcome [2] 335014 0
Salivary immunoglobulin A concentration - additional primary outcome. sIgA will be measured using in-house ELISA method.
Timepoint [2] 335014 0
Within 30 minutes before and 30, 150 and 210 minutes after consumption of 1,3-butanediol.

Eligibility
Key inclusion criteria
Recreationally active male athletes; 18 – 35 years; habitually consuming a mixed diet for at least 1 year; weight stable for at least 1 month.
Minimum age
18 Years
Maximum age
35 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Possess cardiovascular, metabolic, neurological, immunological or autoimmune disorders; baseline haematological values (leukocytes and erythrocyte counts) outside of normal range; experienced illness and/or upper respiratory symptoms within the previous 4 weeks; experienced gastrointestinal symptoms within the previous 4 weeks or has a history of gastrointestinal symptomology; consumed medications or supplements known to effect immunity within previous two weeks; smoker or previously smoked; family member has died before the age of 50 due to a heart condition.

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)
Participants will be allocated to each dose of 1,3-butanediol (0, 0.5, 0.7 or 0.35 + 0.35g/kg) in a randomised order following their inclusion into the study. The primary researcher will not know the order of treatment for the participant during the participant screening process. Each trial arm will be allocated a number from 1 - 4. The day prior to the participant arriving for each trial arm, the investigator will generate a number (via random number generator) from 1 - 4 that will specify what dose of 1,3-butanediol will be used. Numbers will continue to be generated until a trial arm is specified that the participant has not yet completed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised random number generator
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Crossover
Other design features
Nil
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistics will be used to determine the centrality and spread of the data. The normality of each data set will be assessed prior to further statistical analysis. Datasets that defy the assumptions of normality will be log-transformed prior to analysis or analysed using non-parametric analysis. A Repeated Measures Anova will be used to identify whether within-group differences occurred. If significance is found, a paired t-test will be used to determine where the effect occurred. Differences between groups will be assessed using an unpaired t-test. Effects sizes will be determined using Cohen’s d effect size statistics; >0.2 (small), >0.5 (moderate) and >0.8 (large). Differences between group means will be analysed using an unpaired t-test. All analysis will be undertaken using the statistical package SPSS (Version 21, SPSS Inc., Chicago, IL), with significance accepted at P < 0.05. Below P = 0.01, P values will be reported as P < 0.01.

Data will be further analysed for clinical significance using magnitude-based inferences.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
26/07/2017
Actual
2/08/2017
Date of last participant enrolment
Anticipated
1/11/2017
Actual
1/09/2017
Date of last data collection
Anticipated
1/12/2017
Actual
28/09/2017
Sample size
Target
6
Accrual to date
Final
6
Recruitment outside Australia
Country [1] 8845 0
New Zealand
State/province [1] 8845 0
Auckland

Funding & Sponsors
Funding source category [1] 296273 0
University
Name [1] 296273 0
Auckland University of Technology
Country [1] 296273 0
New Zealand
Primary sponsor type
University
Name
Auckland University of Technology
Address
17 Antares Place, Rosedale, Auckland, 0632
Country
New Zealand
Secondary sponsor category [1] 295191 0
None
Name [1] 295191 0
Address [1] 295191 0
Country [1] 295191 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297508 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 297508 0
Ethics committee country [1] 297508 0
New Zealand
Date submitted for ethics approval [1] 297508 0
24/02/2017
Approval date [1] 297508 0
21/04/2017
Ethics approval number [1] 297508 0
17/NTB/39

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

Contacts
Principal investigator
Name 74270 0
Mr David Shaw
Address 74270 0
17 Antares Place, Second Level, Sports Performance Research Institute of NZ (SPRINZ), Rosedale, Auckland, 0632
Country 74270 0
New Zealand
Phone 74270 0
+64 21 0827 6137
Fax 74270 0
Email 74270 0
nutrition@daveshaw.co.nz
Contact person for public queries
Name 74271 0
David Shaw
Address 74271 0
17 Antares Place, Second Level, Sports Performance Research Institute of NZ (SPRINZ), Rosedale, Auckland, 0632
Country 74271 0
New Zealand
Phone 74271 0
+64 21 0827 6137
Fax 74271 0
Email 74271 0
nutrition@daveshaw.co.nz
Contact person for scientific queries
Name 74272 0
David Shaw
Address 74272 0
17 Antares Place, Second Level, Sports Performance Research Institute of NZ (SPRINZ), Rosedale, Auckland, 0632
Country 74272 0
New Zealand
Phone 74272 0
+64 21 0827 6137
Fax 74272 0
Email 74272 0
nutrition@daveshaw.co.nz

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
No documents have been uploaded by study researchers.

Documents added automatically
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