The study will investigate whether taking a prebiotic for six weeks helps to reduce morning cortisol levels in healthy young adults with mild to moderate stress compared to a placebo. Individuals should continue with their usual lifestyle during the study. Other factors of wellbeing will also be assessed.
PROMOTE is a double blinded parallel randomised controlled-trial investigating if prebiotic supplementation reduce awakening salivary cortisol response, reported as area under the curve compared to a maltodextrin placebo in healthy young adults with a mild-to-moderate self reported stress score. There will be a focus on biological secondary outcomes to better understand how supplementation may influence the microbiome using metabolomics and sequencing techniques. In addition to other measures of wellbeing captured by questionnaires and activity monitors.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
70
WellBiome® prebiotic complex: Inulin 67%, XOS 27%, Magnesium Chloride (MgCl2) 9.8 %
Placebo
NIHR Southampton Clinical Research Facility
Southampton, Hampshire, United Kingdom
Salivary Cortisol Awakening Response - Biological salivary cortisol (µg/dL)
Salivary Cortisol Awakening Response (µg/dL) Measured on awakening and hereafter at 0, 15 , 30, 45 minutes Quantified by ELISA and presented as area under the curve, for each timepoint. Example outcome: 'Awakening salivary cortisol response was significantly lower in the prebiotic group compared to the placebo mean difference: -2.27( 95CI-3.68, -0.87) group after 6 weeks of supplementation.' \[result sourced from clinicaltrials.gov NCT0521254\]
Time frame: 6 collections across two working mornings per timepoint. (2 'baseline' - week 0 before supplementation; 2 'endpoint' - week 6 of supplementation ; 2 'follow-up' - within 3rd week (week 9) of supplement end)
Good Sleeper Scale -15 items (GSS -15) self-reported sleep.
GSS-15 - Manners, J et al (2023) questionnaire A 15 item questionnaire validated in a population of Australian adults to give a self-reported indices of sleep on a scale of confidence of being a good sleeper. 10.1111/jsr.13717 GSS-15 ≥ 45: High confidence of being a Good Sleeper GSS-15 40 - 44: Moderate confidence of being a Good Sleeper GSS-15 \< 40: Low confidence of being a Good Sleeper Example outcome: 'There was no difference in the mean reported good sleeper score (43.25 43.25 (95% CI: -40.1, 46.2) of the prebiotic and placebo groups after 6 weeks of supplementation.'
Time frame: 3 timepoints 'Baseline','Endpoint' and 'Follow-up' visits 0,6 and 10 weeks respectivley
Depression Anxiety and Stress Scales 42-items (DASS-42) questionnaire. Wellbeing and subjective mental health assessment.
Depression, Anxiety and Stress Scales Lovibond, P. F., \& Lovibond, S. H. (1995) 10.1016/0005-7967(94)00075-u Scale Scores: DASS (42) Scores are calculated for each subset of the survey with the scale as follows where lower scores indicate a better outcome, while higher scores indicate worse results: Depression Anxiety Stress Normal 0-9 0-7 0-14 Mild 10-13 8-9 15-18 Moderate 14-20 10-14 19-25 Severe 21-27 15-19 26-33 Extremely Severe 28+ 20+ 34+ Example outcome: 'There was a significant reduction in the stress score observed in the prebiotic group (mean: -3.25 (p=0.004) after 6 weeks of supplementation when compared to the placebo group.'
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Time frame: 3 timepoints 'Baseline','Endpoint' and 'Follow-up' visits 0,6 and 10 weeks respectivley
Faceal microbial sequencing and interventional group microbiota compositional change
16S ribosomal ribonucleic acid (rRNA) sequencing of stool samples measuring microbial composition change. Units: Read counts, Operational Taxanomic Units (OTUs) and Relative abundance provide quantifications of the amount of bacterial genetic sequence present in a stool sample building an approximation of the faecal microbial composition to at least the genus level. Results are typical reported in compositional scores like alpha and beta diversity. Bray-Curtis dissimilarity is a scale of similarity where values closer to 1 are more distinct, while values close to 0 represent similar compositions. Example outcome: 'The beta diversity (a measure of compositional change) of the prebiotic group using Bray-Curtis dissimilarity increased by 22.7%, suggesting a compositional change from the placebo group.'
Time frame: Participant home collection, 3 collections:24 hours before 'baseline visit' week 0, 24 hours before 'endpoint visit' week 6, 24 hours before follow-up visit (week 10).
Short Food Frequency Questionnaire (SFFQ): Diet quality score
Validated SFFQ for adults in the United Kingdom (UK) Cleghorn, CL. et al (2017) - University of Leeds Scores per subgroup (Fruit, Vegetables, Oily Fish, Fat and Non-Milk Extrinsic Sugars (NMEs)) are converted to scores ranging from 1-3 based on consumption. Lower scores indicating less intake, while scores of 3 indicate high intake of particular food groups (except for fats and NMEs which is reverse scaled - lower score matching closer to nutritional guideline). A final dietary quality score score is calculated from all subgroups with higher scores indicating better dietary quality. Example outcome: 'Dietary quality scores did not significantly differ among the prebiotic and placebo groups after 6 weeks. This indicates that participants' dietary habits remained consistent throughout the intervention, thereby minimizing dietary intake as a confounding factor in the comparison of the interventional groups.'
Time frame: 3 timepoints 'Baseline','Endpoint' and 'Follow-up' visits 0,6 and 10 weeks respectivley
Activity monitoring using activewear devices
Subsample analysis of biometric activity and sleep using FitBit Inspire 3.0. The Fitbit Inspire 2.0 can capture more objective measures of sleep including time spent in REM sleep phases, sleep duration, awakening and sleep latency. Example outcome: 'Sleep latency, defined as the time taken to fall asleep, was significantly reduced by 5.5 minutes (p \< 0.05) after 6 weeks of prebiotic supplementation compared to the placebo group.'
Time frame: Continuous / 3 nights per 14 days (2 weeknights, 1 weekend night) depending on participants preference.
Urine Metabolomics (Untargeted)
Untargeted Proton Nuclear Magnetic Resonance (1H NMR) metabolomic analysis of urine samples. NMR generates a spectrum of metabolites by detecting hydrogen atoms' response to an electromagnetic pulse. The resulting peaks correspond to specific chemical shift ranges (δ shifts), allowing for the identification of metabolite compositions. It is untargeted as identification is based on what is returned in spectral form, as opposed to targeted which preselects specific metabolites to measure. Example outcome: 'After 6 weeks of prebiotic supplementation, we observed significant increases in the urinary levels of dimethylglycine, indole-3-sulfate, and hippurate compared to the placebo group. These findings suggest that prebiotic supplementation may influence various metabolic pathways and gut microbiota activity.'
Time frame: Participant home collection, 3 collections:24 hours before 'baseline visit' week 0, 24 hours before 'endpoint visit' week 6, 24 hours before follow-up visit (week 10).
Faeces Metabolomics (Untargeted)
Untargeted Proton Nuclear Magnetic Resonance (1H NMR) metabolomic analysis of faeces. NMR generates a spectrum of metabolites by detecting hydrogen atoms' response to an electromagnetic pulse. The resulting peaks correspond to specific chemical shift ranges (δ shifts), allowing for the identification of metabolite compositions. It is untargeted as identification is based on what is returned in spectral form, as opposed to targeted which preselects specific metabolites to measure. Example outcome: 'After 6 weeks of prebiotic supplementation, we observed significant increases in the faecal levels of alanine and glutamate compared to the placebo group. More targeted approaches would be needed to quantify and determine if these amino acids are from dietary, human or microbiome origins like Liquid Chromatography Mass Spectrometry LC-MS).'
Time frame: Participant home collection, 3 collections:24 hours before 'baseline visit' week 0, 24 hours before 'endpoint visit' week 6, 24 hours before follow-up visit (week 10).
Plasma Metabolomics (Untargeted)
Untargeted Proton Nuclear Magnetic Resonance (1H NMR) metabolomic analysis of plasma samples. NMR generates a spectrum of metabolites by detecting hydrogen atoms' response to an electromagnetic pulse. The resulting peaks correspond to specific chemical shift ranges (δ shifts), allowing for the identification of metabolite compositions. It is untargeted as identification is based on what is returned in spectral form, as opposed to targeted which preselects specific metabolites to measure. Example outcome: 'After 6 weeks, prebiotic supplementation significantly increased faecal levels of alanine and glutamate compared to placebo, while lysine levels remained unchanged. Further targeted analyses, such as LC-MS, are needed to determine the origins and concentrations of these amino acids'.
Time frame: 3 timepoints 'Baseline','Endpoint' and 'Follow-up' visits 0,6 and 10 weeks respectivley
Anthropometrics - Body composition
Height (cm), Weight (Kg), Waist Circumference (cm) and Body Mass Index (BMI (kg/m2) Example outcome: 'Mean waist circumference (cm) did not differ significantly (p \> 0.05) between the prebiotic and placebo groups after 6 weeks, suggesting that the prebiotic had no effect on body composition in terms of waist circumference.'
Time frame: 3 timepoints 'Baseline','Endpoint' and 'Follow-up' visits 0,6 and 10 weeks respectivley
Adverse effects monitoring
Monitoring or reporting of any adverse or severe adverse effects experienced during intervention. Reported and logged in active survey responses / contacting the study team directly Example outcome: 'There were two minor side effects reported early in the prebiotic supplementation, both instances self resolved within a few days and may be an effect of the initial introduction of a supplement to the individuals digestive system. No severe adverse effects were reported in either the prebiotic or the placebo control groups.'
Time frame: Continuous monitoring from start to end of study for all participants