RIGHTWHEY - Responders In Gut HealTh Markers Using Fermented WHEY

Healthy Clinical Trial

— RIGHTWHEY  

Official title:

Investigating the Effect of Fermented Whey Concentrate on Gut Microbial Activity: Does Butyrate Matter?

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03844152
• Other study ID #: 808
• Status: Terminated
• Phase: N/A
• Start date: March 13, 2019
• Est. completion date: April 8, 2020

Study information

• Verified date: November 2020
• Source: University of Aberdeen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This 8-week intervention will investigate the effect of daily consumption of a fermented whey concentrate on the short-chain fatty acid profile of faeces in healthy individuals.

This study will help us understand if consumption of fermented foods rich in lactic acid have a beneficial effect on gut health.

Description:

The 8-week dietary supplementation trial will investigate the action of exogenous lactic acid consumption on the activity (using short-chain fatty acid) and composition of the gut microbiota.

Participants will be stratified according to their baseline faecal butyrate levels. Therefore volunteers will be asked to provide two faecal samples one week apart. Based on the average absolute level of butyrate in the faecal samples, volunteers will be stratified into either low, moderate or high baseline butyrate levels (detailed in table 1 below). The levels for faecal butyrate for each group are set based on a meta-analysis of 9 human studies of healthy volunteers carried out at the Rowett Institute (n=116; LaBouyer et al, 2016, unpublished). Thresholds were derived from the boundaries of tertiles. Therefore, the moderate butyrate producers represent the middle 33% (see table). Each stratification arm will have a minimum of 17 study volunteers bringing the total to n=51. This has been set to ensure the completion of at least 45 volunteers. To optimise equal gender distribution amongst all study arms a minimum of 5 females and 5 males will be recruited for each arm.

Stratification Butyrate range Low ≤13 mM Moderate butyrate 13 - 20mM High butyrate ≥20mM

Primary and secondary outcomes will be analysed between the low and high butyrate producing groups as well as the overall group effect on everyone.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 43
• Est. completion date: April 8, 2020
• Est. primary completion date: April 8, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 68 Years

Eligibility

Inclusion Criteria:

• i. Men and women aged 18-68 years; BMI ranging from 18-35 kg/m2; measured at the screening visit

Exclusion Criteria:

• i. smokers

• ii. subjects with: diagnosis of diabetes, pregnant, hypertension, renal, hepatic, haematological disease, coronary heart disease or any gastrointestinal disorder

• ii. unsuitable veins for blood sampling;

• iii. inability to speak, read and understand English.

• iv. Use of antibiotics within the last 3 months will automatically exclude volunteers.

• v. Vegans. Fermented whey concentrate, (FWC), is derived from milk (animal product) which excludes potential participants adhering to a vegan diet.

• vi. allergy to any of the following: cow milk, lactose, casein, whey, sucralose, acesulfame K, citric acid, potassium benzoate, fruit flavourings.

Related Conditions & MeSH terms

• Communicable Diseases
• Health, Subjective
• Healthy
• Infection
• Microbial Colonization

Intervention

Dietary Supplement:
• Fermented whey concentrate
The investigated dietary supplement is a form of lacto-fermented whey concentrate (FWC), which has been deproteinised and then diluted (1/20) in sugar-free flavoured water to improve palatability. The main solute within the lacto-fermented whey is L-(+)-lactic acid (7%), produced through bacterial fermentation of the milk sugar lactose. The research team will provide non-descriptive bottles of drink to all volunteers. The flavour of the FWC will be masked by the flavoured water. In order to assess compliance and minimize an initial treatment effect, a 14 day run-in period during which only flavoured water is to be consumed will be completed by all volunteers. At the same time, this period will act as a wash-out, as volunteers will be asked to abstain from the use of any dietary supplements during this period and the rest of the study. The daily energy content of the FWC is 4kcal.

Locations

Country	Name	City	State
United Kingdom	The Rowett Institute, Human Nutrition Unit	Aberdeen

Sponsors (2)

Lead Sponsor	Collaborator
University of Aberdeen	A. Vogel

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Faecal butyrate concentration - comparing upper and lower tertile of volunteers	Change in relative proportion of butyrate (percentage of total SCFA - sum of propionate, butyrate, acetate, valerate, iso-valerate, iso-butyrate, succinate, lactate mM (millimolar values from gas chromatography) and absolute concentration (mM millimolar) when comparing volunteers as stratified by faecal butyrate levels at start of study. A comparison will be made between the butyrate concentration-dependent groupings.	Baseline measurement (Visit 1) and end of study (visit 3, 8 weeks later) [Baseline butyrate calculated from the average of two values per individual at Day -7 and Day 0; End of study value is the average from two samples collected at Day 49 and 56
Primary	Faecal butyrate concentration - intervention group effect	Change in relative proportion of butyrate (percentage of total SCFA) and absolute concentration (mM, millimolar) across the total study group	Baseline measurement (Visit 1) and end of study (visit 3, 8 weeks later) [Baseline butyrate calculated from the average of two values per individual at Day -7 and Day 0; End of study value is the average from two samples collected at Day 49 and 56
Primary	Microbiota composition change	Changes in the composition of the microbiota will be based on next-generation sequence analysis of 16S rRNA (ribosomal ribonucleic acid) genes extracted from faecal samples provided by all volunteers	Assessed as change between day 0 and day 56
Secondary	Gastrointestinal wellness questionnaire	Changes in frequency or consistency of bowel movements and gastrointestinal well being will be assessed with a self-administered weekly questionnaire (ranked on a linear likert scale).; The questionnaire asks volunteers to rank nausea, bloating, flatulence, abdominal cramps, rumbling, indigestion, fullness/distension and early satiation over the last 24 hours. The scale is scored from -3 being considerably less, -2 moderately less, -1 for slightly less and 0 for as usual. Responses such as slightly more are scored as 1, moderately more as 2 and considerately more as 3.; Scores will be aggregated across all categories and compared as a whole to represent general GI wellness changing throughout the intervention.; Participants have a blank box to fill in with the number of bowel movements in the last 24hr and are asked to rank them on the Bristol stool scale (0-7, visual guide included in the questionnaire). Scores will be assessed as averages over the control and intervention periods.	Day 0, 7, 14, 21, 28, 35, 42, 49 and 56
Secondary	Glucose tolerance and insulin sensitivity	Comparison of change in response to Oral glucose tolerance test (3 hours) using the total and incremental area under the curve (AUC)for both glucose and insulin concentrations.; Both values are measured in arbitrary units and calculated by the standard trapezoid method.; Incremental AUC is the baseline corrected output for total AUC.; Comparison will be made between group averages at baseline and post-intervention	Measured on Day 0 and Day 56
Secondary	Health related quality of life questionnaire	Change in score in health-related quality of life questionnaire General health is ranked on a scale of excellent, very good, good, fair and poor with scores ranging from 1 - 5 respectively.; Volunteers are asked to write the relevant days they have been affected by: physical health, mental health or impaired by poor mental and physical health, or pain over the last 30 days.; Participants are asked to respond to the following questions relating to the past 30 days: how many days have they felt sad/blue, worried/tense/anxious, did not have enough rest/sleep and have felt very healthy and full of energy.; Each category will be individually compared at baseline and post-intervention.	scored on Day 0 and 56
Secondary	Small intestinal fermentation	Change in Breath test assessment of hydrogen and methane levels (given in ppm - parts per million) and faecal pH (using standard pH meter)	measured on Days 0, 14 and 56
Secondary	Faecal pH	Change in Faecal pH, using standard pH meter - Scale 0-14	measured at day 0 and 56
Secondary	Faecal moisture content	proportion of faeces (in the percentage of total weight) made up of water	measured at day 0 and 56