PROMOTE: The Effect of a Six Week Probiotic or Prebiotic Supplementation on Wellbeing of Young Adults.
NCT Number: NCT06566157
Acronym: PROMOTE
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Wellbeing|Healthy
Interventions: DIETARY_SUPPLEMENT: Probiotic|DIETARY_SUPPLEMENT: Prebiotic|DIETARY_SUPPLEMENT: Maltodextrin (Corn)
Sponsor: University of Southampton
Collaborators: OptiBiotix Health Plc
Sex: ALL
Age: ADULT
Enrollment: 105
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-09-16
Completion Date: 2026-09-16
Locations: NIHR Southampton Clinical Research Facility, Southampton, Hampshire, SO16 6YD, United Kingdom

Summary:
The study will investigate whether taking either a probiotic or 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.

Primary Outcome Measures: 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 probiotic group compared to the placebo mean difference: -2.27( 95CI-3.68, -0.87) group after 6 weeks of supplementation.' \[result sourced from clinicaltrials.gov NCT0521254\], 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)
Secondary Outcome Measures: 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 probiotic and placebo groups after 6 weeks of supplementation.', 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 probiotic group (mean: -3.25 (p=0.004) after 6 weeks of supplementation when compared to the placebo group.', 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.', 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 probiotic, 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.', 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.', 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 probiotic 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 probiotic supplementation may influence various metabolic pathways and gut microbiota activity.', 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 probiotic 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).', 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, probiotic and 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'., 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.', 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 probiotic 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 any of the interventional groups - probiotic, prebiotic or the placebo control.', Continuous monitoring from start to end of study for all participants
Other Outcome Measures: Urine Metabolomics (Targeted), Targeted metabolomics using Gas Chromatography - Mass Spectrometry/ Liquid Chromatography - Mass Spectrometry (GC-MS/LC-MS) of urine samples following untargeted results. Biocrates Kits / neurobiological metabolites or their breakdown products i.e. 5-Hydroxyindoleacetic acid (serotonin), kynurenic acid (tryptophan).

Metabolites are typically quantified in the in micrograms per millilitre concentration range (µg/mL).

n= 315 samples in total across the three timepoints.

Example outcome:

'Using GC-MS we saw a significant change in the concentration of kynurenic acid \[amount specified (µg/mL)\] between the prebiotic and placebo groups.', 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 (Targeted), Targeted metabolomics using Gas Chromatography - Mass Spectrometry/ Liquid Chromatography - Mass Spectrometry (GC-MS/LC-MS) of stool samples untargeted results. D-L amino acid assays - to determine microbial metabolites (D-glutamate, D-alanine, D-lysine)

Metabolites are typically quantified in the nanomolar per gram concentration range (nmol/g).

n= 315 samples in total across the three timepoints.

Example outcome:

'Using GC-MS we saw a significant change in the concentration of D-lysine \[amount specified (nmol/g)\] between the probiotic and placebo groups', 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 (Targeted), Targeted metabolomics using Gas Chromatography - Mass Spectrometry/ Liquid Chromatography - Mass Spectrometry (GC-MS/LC-MS) of plasma samples following untargeted results.

D-L amino acid assay, neurobiological metabolites and short-chain fatty acids (typically produced from prebiotics - Acetate, Propionate and Butyrate).

Metabolites are typically quantified in the in micrograms per millilitre concentration range (µg/mL).

n= 315 samples in total across the three timepoints.

Example outcome:

'Using GC-MS we saw a significant change in the concentration of Acetate \[amount specified (µg/mL)\] between the prebiotic and placebo groups.', 3 timepoints 'Baseline','Endpoint' and 'Follow-up' visits 0,6 and 10 weeks respectivley