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Trial registered on ANZCTR


Registration number
ACTRN12620000411943
Ethics application status
Approved
Date submitted
13/03/2020
Date registered
27/03/2020
Date last updated
27/03/2020
Date data sharing statement initially provided
27/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
SMART Study: Sleep, Microbiota And fRuiT Study
Scientific title
Determining the effects of fresh kiwifruit versus dried whole kiwifruit powder on sleep quality in male poor sleepers: a 2-week randomised controlled single-blind clinical trial
Secondary ID [1] 297698 0
None
Universal Trial Number (UTN)
U1111-1244-3459
Trial acronym
SMART Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Poor sleep
311994 0
Condition category
Condition code
Diet and Nutrition 310559 310559 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will consume, in randomised, single-blind fashion (cross-over design), three different interventions, i) two fresh green kiwifruit (200g), ii) freeze-dried green kiwifruit powder (32g) (equivalent to two whole kiwifruits) mixed with 170ml water or iii) water 170ml (control). Each participant will receive 14 days worth of intervention to consume for 14 days, and treatments i, ii and iii will occur on separate occasions with a 14 day washout period in between. Measures of sleep quality will be determined at the start of each treatment (day 0), at the end of each treatment (day 14) and the end of each washout period (day 28). During study laboratory visits, the lead researchers will be present to monitor adherence to study protocol carefully. On each study day, subjects will be in the laboratory-based assessments at 17:00 hr and will complete surveys and questionnaires. Immediately following the first questionnaire, participants will have a venous cannula inserted and a blood sample taken. Blood samples will be collected every hour until bedtime. At 18:00 hr a standardised dinner is served and is to be consumed within 30min. After dinner intervention i, ii or iii is served. Profile of Mood States (POMS) will be completed on arrival 17:00 hr, before bedtime 22:00 hr and waking 07:00 hr. Upon waking, single blood, urine and faecal sample will be collected. Lastly, a cognitive battery will also be completed at waking, after this participant will be allowed to leave the laboratory. Compliance will be ensured by asking participants to return unconsumed items on day 14 of each dietary intervention period and filling out daily checklist forms indicating the time the intervention was consumed. A text message reminder will be sent daily to remind the participants to consume the intervention.
Intervention code [1] 313929 0
Treatment: Other
Comparator / control treatment
The control will be water with nothing added to it.
Control group
Placebo

Outcomes
Primary outcome [1] 319417 0
Change in sleep quality
Timepoint [1] 319417 0
Actigraphy watches will be used on the non-dominant arm for the entire duration of the study (approx. 12 weeks). This will give four objective sleep variables of sleep onset latency, wake after sleep onset, total sleep time and sleep efficiency daily for the entire period of the study.
Primary outcome [2] 323218 0
Changes in Dim Light Melatonin Onset in plasma
Timepoint [2] 323218 0
Hourly blood samples will be collected in a dim light setting (10lx) upon arrival until participants sleep. Melatonin in the plasma will be quantified using ELISA kit. Blood collections are at baseline, 14 days after intervention consumption and 14 days after a washout on each intervention.
Primary outcome [3] 323278 0
Changes in 6-sulfatoxymelatonin in urine
Timepoint [3] 323278 0
Frist morning void urine samples will be used to quantify 6-sulfatoxymelatonin using ELISA kit. Urine collections are at baseline, 14 days after intervention consumption and 14 days after a washout on each intervention.
Secondary outcome [1] 368079 0
Changes in mood
Timepoint [1] 368079 0
The mood will be assessed using the Profile of Mood States (POMS) survey. Mood assessment will be conducted at baseline, 14 days after intervention consumption and 14 days after washout.
Secondary outcome [2] 369548 0
Changed in targeted metabolomic plasma analyses of 72 metabolites will be undertaken with high-performance liquid chromatography mass spectrometry.
Timepoint [2] 369548 0
At each of the overnight sleeps in the laboratory, eight blood samples hourly and a single will be collected. Metabolites and neurotransmitters will be determined in blood using targetted metabolomics. This includes 5-Hydroxyindoleacetic acid, 5-Hydroxytryptophol, N-Acetylserotonin, Tryptophan, Leucine, Lysine, Isoleucine, Alanine, Methionine, Proline, Threonine, Valine, Asparagine, Histidine, Arginine, Tyrosine, Phenylalanine, Cysteic acid, Choline, 3,4-Dihydroxyphenylacetic acid, 3-Methoxytyramine, Homovanillic acid, 3,4-Dihydroxyphenylalanine, Carnosine, Anserine, Kyotorphin, Citrulline, Ornithine, Acetylcholine, 3-Hydroxyanthranilic acid, Homocysteine, 3,4-Dihydroxymandelic acid, Normetanephrine, 3,4-Dihydroxyphenylglycol, 3-Methoxy-4-hydroxyphenylglycol, Vanillylmandelic acid, Cysteine, Glutamine, Glutamate, Aspartate, Glycine, Serine, B-Alanine, Kynurenic acid, 3-Hydroxykynurenine Serotonin, Dopamine, 4-Aminobutyric acid, Histamine, Melatonin, Taurine, Norepinephrine, Epinephrine, Homoserine, Adenosine, Synephrine, Putrescine, Spermidine, Spermine, N-Acetylputrescine, Agmatine, Hypotaurine, Homocysteic acid, Glucose, Tyramine, Phenethylamine, Tryptamine, Octopamine, Glutathione, Kynurenine, 5-Hydroxytryptophan and Ethanolamine. Blood collections are at baseline, 14 days after intervention consumption and 14 days after a washout on each intervention.
Secondary outcome [3] 369549 0
Changes in gut microbiota
Timepoint [3] 369549 0
At each of the overnight sleeps in the laboratory, a single faecal sample will be collected. DNA is extracted from the faecal sample, and the relative abundance of gut microbiota is determined by next-generation sequencing analysis. Faecal sample collections are at baseline, 14 days after intervention consumption and 14 days after a washout on each intervention.

Secondary outcome [4] 381412 0
Changes in stress
Timepoint [4] 381412 0
The Kessler Psychological Distress Scale (K10) will be used to measure stress. Stress assessment will be conducted at baseline, 14 days after intervention consumption and 14 days after washout.
Secondary outcome [5] 381413 0
Changes in cognitive performance
Timepoint [5] 381413 0
The cognitive testing will use the Cambridge Neuropsychological Test Automated Battery (CANTAB) software. Cognitive assessment will be conducted at baseline, 14 days after intervention consumption and 14 days after washout.

Eligibility
Key inclusion criteria
Healthy males
Aged between 18-45 years of age
Body mass index (BMI) (18.5-30kg/m2)
Physically active but no more than 2 hours per day
Poor sleepers, defined as having an ISI (Insomnia Severity Index) score of >8 (Ree, Pollitt, & Harvey, 2006) and the Pittsburgh Sleep Quality Index (PSQI) score >5 (Buysse, Reynolds III, Monk, Berman, & Kupfer, 1988)
Glycated haemoglobin (HbA1c) test, value <41mmol/mol (greater than this is considered prediabetes) (Braatvedt et al., 2012)
Minimum age
18 Years
Maximum age
45 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Use of specific prescribed medication as listed below or recreational drugs use:
Diuretics, Oral or inhaled steroids, Cholinergic antispasmodics, Lactulose, Metamucil, Antibiotics, Sedative/hypnotic medication, Laxatives, Antacids, Cholesterol-lowering medications, Proton pump inhibitors (acid reflux treatments), Vitamin/mineral supplements, Heparin, Antidepressants
Excessive alcohol intake defined as >20g of pure alcohol (2 drinks)/d on average. (>21 standard drinks a week)
Smoke cigarettes
History of gastrointestinal surgery or gastrointestinal disorders including inflammatory bowel disease (IBD), ulcerative colitis, coeliac disease, Crohn’s disease
Medical conditions (e.g., cardiorespiratory, diabetes mellitus, bleeding disorders)
Psychiatric conditions (e.g., Major depressive disorder, Schizophrenia)
Antibiotic consumption (1 month before the study and during the study)
Significant weight loss during the past six months
Being on a controlled diet or dietary weight loss regimen within four weeks before and during the study
Vegetarian/vegan
Aversion to blood sampling
Allergies to dairy products or eggs or fruits
Participants will be asked to abstain from alcohol before attending a sleep session at the laboratory and to abstain from caffeinated beverages and vigorous exercise eight hours before their averaged bedtimes

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)
Eligible volunteers are assigned a subject number and randomised onto a treatment visit schedule based on a Latin square design balanced for the order of presentation and carry-over effect. Treatments will be assigned a code. The treatment code will be held by two scientists who are not responsible for treatment dispensing or data collection. The unblinded scientists are responsible for allocating a random treatment position to the volunteers and preparing the study interventions.



Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation plan for assigning volunteers onto the Latin square design is generated using a randomization plan generator available at https://www.randomizer.org/
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Demographic and anthropometric characteristics will be summarized using descriptive statistics. All outcome variables will be analysed using a mixed-effects linear model ANOVA to account for the repeated measurements that yield period, sequence, and carryover effects and to model the various sources of intra-patient and inter-patient variability. Where the repeated measures linear mixed model ANOVA is significant, Tukey’s post hoc analysis will be used for comparisons between conditions.

A power analysis was performed to provide estimates of variance components using data from Lin et al. 2011, where two green kiwifruits were given, and sleep was measured. Calculations were done on the primary endpoint of sleep onset latency, total sleep time and sleep efficiency. In the current study, it is anticipated that 18-24 participants will be required to complete the three treatment arms. The model based upon an estimated error variance was taken from Lin et al. 2011 and calculated, using the power of 0.8 suggests that the number of subjects required is estimated to fall between 18-24 participants. Given the potential for participants to withdraw from the study, recruiting 24 people will allow for 80% power even after potential withdraws.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 21981 0
New Zealand
State/province [1] 21981 0
Auckland

Funding & Sponsors
Funding source category [1] 302222 0
Other
Name [1] 302222 0
Riddet Institute
Address [1] 302222 0
Riddet Institute
Massey University
Tennent drive
Palmerston North
New Zealand
4442
Country [1] 302222 0
New Zealand
Primary sponsor type
University
Name
Massey University
Address
Massey University Manawatu (Turitea)
Tennent Drive
Palmerston North 4474
New Zealand
Country
New Zealand
Secondary sponsor category [1] 302834 0
None
Name [1] 302834 0
Address [1] 302834 0
Country [1] 302834 0
Other collaborator category [1] 281016 0
Other Collaborative groups
Name [1] 281016 0
NZ Respiratory & Sleep Institute
Address [1] 281016 0
Ascot Office Park
93-95 Ascot Ave
Greenlane East
Auckland 1051
Country [1] 281016 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302902 0
Massey University Human Ethics
Ethics committee address [1] 302902 0
Research Ethics Office
Massey University
Tennent Drive
Palmerston North 4474
Ethics committee country [1] 302902 0
New Zealand
Date submitted for ethics approval [1] 302902 0
18/11/2019
Approval date [1] 302902 0
19/03/2020
Ethics approval number [1] 302902 0
SOA 19/78

Summary
Brief summary
The primary objective of this research is to investigate how long term KF consumption may impact sleep quality and its downstream effects on cognition, mood, stress, metabolites and gut microbiota. KF contain a protein named actinidin, which is a protease enzyme involved in enhancing digestion of proteins into amino acids. Some of these amino acids are precursors of neurochemicals required for sleep-wake regulation. KF is a known source of folate and vitamin C, which is essential in the metabolism of amino acids into neurochemicals. Consumption of kiwifruit (KF) one hour before bed improves sleep as measured by actigraphy. However, this study does not provide evidence on how sleep quality and biochemical measures may be affected.

A randomised, single-blind, controlled, crossover trial is planned. Participants will consume a control (water), two fresh green KF or a dried green kiwifruit powder (equivalent to two fresh green KF). An activity monitor on the non-dominant arm will be used for sleep assessment and mood/stress/cognitive tests will be completed. Measures will be conducted on each intervention after 14 days of intervention consumption, and 14 days after washout. Blood and urine will be collected and analysed for metabolites and faecal samples sequenced for microbial populations and metabolites. This study will allow a better understanding of how KF consumption may improve sleep and assist in understanding a possible mechanism.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91786 0
Mr Alex Kanon
Address 91786 0
Riddet Institute
Massey University
Private Bag 11222
Palmerston North 4442
Country 91786 0
New Zealand
Phone 91786 0
+64 6 951 7742
Fax 91786 0
Email 91786 0
a.kanon@massey.ac.nz
Contact person for public queries
Name 91787 0
Dr Sharon Henare
Address 91787 0
School of Health Sciences
College of Health
Massey University
Private Bag 11222
Palmerston North 4442
Country 91787 0
New Zealand
Phone 91787 0
+64 6 3569099 84289
Fax 91787 0
Email 91787 0
S.J.Henare@massey.ac.nz
Contact person for scientific queries
Name 91788 0
Prof Warren McNabb
Address 91788 0
Riddet Institute
Massey University
Private Bag 11222
Palmerston North 4442
Country 91788 0
New Zealand
Phone 91788 0
+64 6 951 7742
Fax 91788 0
Email 91788 0
W.McNabb@massey.ac.nz

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?
No other documents available
Summary results
No Results