Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001611819
Ethics application status
Approved
Date submitted
12/10/2021
Date registered
26/11/2021
Date last updated
31/10/2022
Date data sharing statement initially provided
26/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of pre-sleep alpha-lactalbumin supplementation in a trained population with sleep difficulties
Scientific title
Effect of pre-sleep alpha-lactalbumin supplementation in a trained population with sleep difficulties
Secondary ID [1] 305537 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sleep difficulty 323926 0
Condition category
Condition code
Mental Health 321439 321439 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study design - Randomised, double-blinded, counterbalanced, crossover design
(Crossover experimental group = 40 g alpha-lactalbumin; Crossover placebo group = 40 g collagen)

As a cross-over trial, to limit any potential carry over effects of the alpha-lactalbumin into the next intervention period, a minimum five night washout period is to be observed. Further, to ensure the influence of female hormones is low throughout the intervention periods (as this can confound sleep outcomes), naturally menstruating females are to complete both intervention periods during the early follicular phase. This phase will be determined through menses and menstrual cycle mapping.

Experimental group - alpha-lactalbumin
Product - BiPRO Alpha 9000 (Agropur Inc, Appleton, WI)
Dose - 40 grams once daily
Duration - 3 days
Dosage form - Powder, oral
Route of Administration - Oral
Active ingredient - Tryptophan (1.9 g)

To investigate the effect of evening supplementation (2 hours prior to sleep) of 40 g alpha lactalbumin the sleep, mood, and cognition of a trained population with sleep difficulties compared to placebo.

Amino acid analysis and melatonin measured within blood plasma to explore potential mechanisms by which alpha-lactalbumin may influence sleep

To control for protein's potential confounding influence on the effectiveness of alpha-lactalbumin supplementation, participants diet will be standardised to meet habitual energy intake, and 1.2 g/kg of body weight of daily protein. This amount is at the lowest end of recommended protein amounts for athletes.

As participants will complete the intervention periods at the Deakin University campus, a member of the research team (or research assistant) will be providing both the supplement and meals to the participants. This means adherence to both the diet and supplement is able to be observed. Further, all meals (3 main meals + 2 snacks) will be provided by a member of the research team, with participants able to consume additional low-protein snacks if they wish to do so (must be replicated by the participant for both intervention periods). The dietary supplement will be mixed up and matched for taste by an external researcher, to ensure both participants and the researcher team remain blind to the treatments.
Intervention code [1] 321934 0
Treatment: Other
Comparator / control treatment
Placebo group - collagen
Product - Collagen Regenerate (Body Science, Burleigh, QLD)
Dose - 40 grams once daily
Duration - 3 days
Dosage form - Powder, oral
Route of Administration - Oral
Active ingredient - Tryptophan (0 g)

As this placebo supplement will be provided to the participants whilst at the University, adherence is able to be observed by researchers.

Both the placebo and experimental group will receive the same standardised meals throughout the intervention period.
Control group
Placebo

Outcomes
Primary outcome [1] 329222 0
Total sleep time (hrs) measured through portable electroencephalography (Dreem 3 headband).
Timepoint [1] 329222 0
Each night across both 3-day supplementation periods.
All timepoints across both intervention periods are considered primary timepoints.
Primary outcome [2] 329489 0
Sleep onset latency (min) measured through portable electroencephalography (Dreem 3 headband).
Timepoint [2] 329489 0
Each night across both 3-day supplementation periods.

All measures across both intervention periods are considered primary timepoints.
Primary outcome [3] 329490 0
Sleep efficiency (%) measured through portable electroencephalography (Dreem 3 headband).
Timepoint [3] 329490 0
Each night across both 3-day supplementation periods.

All measures across both intervention periods are considered primary timepoints.
Secondary outcome [1] 401812 0
Cognitive performance as assessed through the smart device app Joggle Research.
Timepoint [1] 401812 0
Each morning and evening timepoint across both intervention periods
Secondary outcome [2] 401813 0
Changes in plasma melatonin levels.

Plasma melatonin will be assessed using ELISA assays.
Timepoint [2] 401813 0
First night of each intervention, with the 60-minute and 120-minute post-supplement consumption timepoints to be compared.

Blood plasma samples will be collected via cannulation on the first night of each intervention period. Blood samples to be used for plasma melatonin levels include the 60 minute and 120 minute post-supplement consumption timepoints.
Secondary outcome [3] 401814 0
Changes in subjective mood scores as assessed via the Brunel Mood Scale.
Timepoint [3] 401814 0
All measured timepoints in the evening and morning are considered as secondary timepoints.

This is to be measured across both 3-day intervention periods, 30 minutes prior to sleep, and 30 minutes upon waking.
Secondary outcome [4] 401815 0
Changes in subjective sleepiness scores as assessed via the Karolinska Sleepiness Scale
Timepoint [4] 401815 0
All measured timepoints in the evening and morning are considered as secondary timepoints.

This is to be measured across both 3-day intervention periods, at 0, 30, 60, 90, and 120-minutes post supplement consumption, and in the morning 30 minutes upon waking.
Secondary outcome [5] 401816 0
Changes in subjective recovery scores as assessed via the Short Recovery and Stress Scale
Timepoint [5] 401816 0
All measured timepoints in the evening and morning are considered as secondary timepoints.

This is to be measured across both 3-day intervention periods, at 30 minutes prior to sleep and in the morning 30 minutes upon waking.
Secondary outcome [6] 402777 0
PRIMARY OUTCOME:
Sleep stage duration (%, hrs) measured through portable electroencephalography (Dreem 3 headband).
Timepoint [6] 402777 0
PRIMARY TIMEPOINT:
Each night across both 3-day supplementation periods.

All measures across both intervention periods are considered primary timepoints.
Secondary outcome [7] 402778 0
PRIMARY OUTCOME:
Rapid eye movement latency (min) measured through portable electroencephalography (Dreem 3 headband).
Timepoint [7] 402778 0
PRIMARY TIMEPOINT:
Each night across both 3-day supplementation periods.

All measures across both intervention periods are considered primary timepoints.
Secondary outcome [8] 402779 0
PRIMARY OUTCOME:
Wake after sleep onset (min) measured through portable electroencephalography (Dreem 3 headband).
Timepoint [8] 402779 0
PRIMARY TIMEPOINT:
Each night across both 3-day supplementation periods.

All measures across both intervention periods are considered primary timepoints.
Secondary outcome [9] 402780 0
PRIMARY OUTCOME:
Changes in the blood plasma tryptophan (TRP): large neutral amino acid (LNAA) ratio.

Amino acid analysis will be completed through LC-QqQ-MS, and the TRP:LNAA ratio will be determined by dividing plasma TRP concentration by the sum of the other LNAAs, i.e., isoleucine, leucine, phenylalanine, tyrosine, and valine.
Timepoint [9] 402780 0
PRIMARY TIMEPOINT:
First day of both intervention periods, with all measured timepoints considered as primary timepoints.

Blood plasma samples will be collected via cannulation on the first night of each intervention period. Five blood samples will be taken on each occasion, including immediately pre-supplement consumption, 30, 60, 90, and 120 minutes post consumption. Changes in the blood plasma TRP:LNAA ratio will be analysed at each of these five timepoints, across both intervention periods.

Eligibility
Key inclusion criteria
Inclusion: Participants must be between 18-40 years old, and currently be completing structured moderate-vigorous exercise at least three times per week for a minimum total of five hours per week to meet “trained athlete” guidelines. Further, participants will be screened using the Athlete Sleep Screening Questionnaire (Appendix 1) and Pittsburgh Sleep Quality Index (Appendix 2), and those with a sleep difficulty score equal to or greater than 5, global PSQI score >5 and a sleep onset latency >15 minutes will be eligible. These scores coincide with equal to or greater than mild sleep difficulty and poor-quality sleep, which are the targeted participants for this study.

Female participants are required to be naturally menstruating or taking an oral contraceptive pill. As female hormone differences across the menstrual cycle can influence sleep, participation will occur during predictable phases where the influence of hormones is low.
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion: smoking, excessive alcohol consumption (>17 standard drinks per week), dairy allergy, high caffeine use (e.g., >5 mg·kg-1·d-1), antidepressant or sleep medication use, current or recently finished night shift work, recent transmeridian travel, fluctuating bedtimes, and pregnancy. These exclusions criteria relate to confounding influences that may affect sleep or the plasma TRP:LNAA ratio.

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)
External researcher outside of research team to generate the sequence by which a participant will complete the crossover conditions. This will ensure both the research team and participant remain blinded to the treatment (i.e., placebo or alpha-lactalbumin) the participant is receiving.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This will be done in a counterbalanced manner through simple randomisation techniques (i.e., coin toss)..
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
Crossover
Other design features
Double-blinded
Randomised
Counterbalanced
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical power calculation - A two-sided t-test achieves 92% power to infer that the mean difference is not 0.0 when the total sample size of a 2x2 cross-over design is 18, the actual mean difference is -0.600, the square root of the within mean square error is 0.5, and the significance level is 0.05.

Statistical analysis - Initially, data cleaning will be performed to identify missing and corrupt data. Data will be analysed using generalised linear mixed models within StataIC 16 (StataCorp LLC, TX, USA). The effect of dietary intervention (i.e., placebo or a-lactalbumin) and period (i.e., sequence receiving condition) and their interaction, will be fitted as fixed effects to determine whether there was a difference in the effect of dietary intervention over period on dependant sleep variables (e.g., sleep efficiency), mood, amino acid analysis and plasma melatonin. As training load will be a potential confounder to the nutrition-sleep relationship, this will be included as a covariate within the linear mixed model. Participant identification number will be used as a random factor to account for repeated measures in each model.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
10/01/2022
Actual
24/10/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
18
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 309904 0
University
Name [1] 309904 0
Deakin University - Centre for Sport Research
Country [1] 309904 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
221 Burwood Hwy, Burwood VIC 3125
Country
Australia
Secondary sponsor category [1] 310935 0
None
Name [1] 310935 0
Address [1] 310935 0
Country [1] 310935 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309626 0
Deakin University Human Research Ethics Committee
Ethics committee address [1] 309626 0
Ethics committee country [1] 309626 0
Australia
Date submitted for ethics approval [1] 309626 0
12/10/2021
Approval date [1] 309626 0
01/03/2022
Ethics approval number [1] 309626 0
2021-372

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

Contacts
Principal investigator
Name 114818 0
Dr Dominique Condo
Address 114818 0
221 Burwood Hwy, Burwood VIC 3125
Deakin University
Country 114818 0
Australia
Phone 114818 0
+61 3 9244 5487
Fax 114818 0
Email 114818 0
[email protected]
Contact person for public queries
Name 114819 0
Dominique Condo
Address 114819 0
221 Burwood Hwy, Burwood VIC 3125
Deakin University
Country 114819 0
Australia
Phone 114819 0
+61 3 9244 5487
Fax 114819 0
Email 114819 0
[email protected]
Contact person for scientific queries
Name 114820 0
Dominique Condo
Address 114820 0
221 Burwood Hwy, Burwood VIC 3125
Deakin University
Country 114820 0
Australia
Phone 114820 0
+61 3 9244 5487
Fax 114820 0
Email 114820 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


What supporting documents are/will be available?




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.