Glycaemic Control
Research type
Research Study
Full title
A double-blind, randomized, placebo-controlled clinical trial to assess the efficacy and safety of 12-weeks daily oral supplementation with Eubacterium hallii on insulin sensitivity and markers of glycaemic control in otherwise healthy hyperglycaemic males
IRAS ID
306752
Contact name
Gordon Crawford
Contact email
Sponsor organisation
Caelus
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 4 months, 31 days
Research summary
Research Summary
This study is an exploratory study to evaluate the effect of 12 week supplementation of E.Hallii on glycaemic control in otherwise healthy males.
The study wishes to further evaluate the efficacy and safety of E. hallii supplementation in a small group of males focusing on the areas of insulin sensitivity and glycaemic control, and with a view to establishing a future health claim for E. hallii in one or more of these health benefit areas.
Participants will be involved in the study for approx. 19 weeks and will attend the clinic for 7 visits within this period.
The study product that will be tested is a probiotic called Eubacterium hallii. This is a live bacteria, that when ingested, may have a positive influence on your health, specifically by improving your bodies ability to regulate your blood sugar levels. Disordered glycaemic control and an elevated waist circumference are associated with health complications, specifically an increased risk of developing diabetes. A simple blood test will be conducted to measure your HbA1c levels, this reflects your bodies ability to control your blood sugar levels over the previous 2-3 months. The study also aims to explore trends in your glucose levels during the day and night over a 2 week period. In order to do this, you will be asked to wear a FreeStyle Libre Pro Flash Gluocse Monitoring Sensor. The research team will give you training and the equipment to do this at your second visit.
There is increasing evidence that the gut microbiome offers an opportunity for the development of novel interventions for a variety of diseases by modifying the composition of the gut microbiome. To determine if the study product positively impacts on metabolic markers by modulating your gut microbiome, it will be tested along with a placebo. Both the probiotic and placebo are similar in appearance, packaging and taste. You will be assigned to one of the study products at random, so you will have a 50% chance of receiving the active treatment and a 50% chance of receiving the placebo product. The study will be conducted under blinded conditions which means that you, nor your research team will know which product you will receive. However, if your study doctor or team need to find out which product you had, he/she/they can do so.
Summary of Results
The treatment of prediabetic subjects with a daily dose of A. soehngenii for three months improved various markers of glycaemic control, reduced HbA1c-levels over an extended period and reversibly reduced diastolic blood pressure over placebo. These results confirm earlier results with different formulations of A. soehngenii, underlining the value of this next generation beneficial microbe for improving cardiometabolic health of subjects at risk of developing type 2 diabetes.
Sensitivity analysis revealed statistically significant between-subject glycaemic control improvements by product (p=0.001) and site (p=0.003) in derived absolute change in post-prandial glucose control (iAUC) and between-subject effects by site (p=0.004) and product*site (p=0.007) in derived absolute change in post-prandial insulin control. A statistically significant change (p=0.005) and product*change interaction (p=0.031) in HbA1c levels were also found at week 16. The greatest improvements in these three primary endpoints were observed in the A. soehngenii group in the USA.Statistically significant changes in FBG levels at week 6, week 16, and from week 12 to 16 were determined in the PP population only (p=0.035, p=0.023, and p=0.040, respectively). Furthermore, a statistically significant correlation between BMI and FBG levels and derived change in fasting glucose levels at week 12 was observed in the Placebo group (p=0.028) in the ITT population. For glycaemic variability coefficient of variation, between region comparisons revealed statistically significant between group differences in derived change at week 12 (p=0.010). The additional CONGA (Continuous Overall Net Glycemic Action) analysis to further investigate glycaemic control showed a statistically significant product*change interaction at week 12 in the total (p=0.045) and in the USA (p=0.032) populations.
Statistically significant between-group differences were observed in diastolic blood pressure in derived change by product at week 12 (p=0.031). This significant finding was not observed in the individual regions due to insufficient statistical power.
Finally, statistically significant increases in absolute and relative abundances of A. soehngenii, formerly E. hallii, were observed between week 0 and week 12 in the Active (p<0.001) but not the Placebo group. At the same time, there was a statistically significant increase from week 0 to week 12 in faecal butyrate levels in the Active group (p=0.020).
SAFETY RESULTS:
A. soehngenii (formerly E. hallii was confirmed to be safe, with no serious adverse events being reported during the study. All reported adverse events (AEs) were of mild or moderate intensity and only six events in total were deemed to be related to the investigational products (three related AEs each for A. soehngenii and placebo). These AEs were unremarkable and were all classified as of mild severity.
Laboratory results were generally unremarkable, the mean safety blood parameters were within normal ranges at all study visits. Individual results were clinically reviewed by the sub-investigator and deemed to be safe at all timepoints. There were no clinically meaningful changes in participants’ anthropometrics or vitals detected during the study.CONCLUSION:
The overall results of the study showed an improvement in markers of glycaemic control in the A. soehngenii group which had clinically relevant effects on post-prandial OGTT derived glucose levels, plasma HbA1c levels, glycaemic variability coefficient of variation, fasting blood glucose levels and diastolic blood pressure. Intervention with A. soehngenii was also found to increase absolute and relative abundance of faecal A. soehngenii at week 12 (p<0.001) as well as faecal butyrate levels (p=0.020). Statistically significant improvements in iAUC glucose levels, glycaemic variability coefficient of variation, and HbA1c levels were observed in the A. soehngenii group compared to placebo in the USA population. The next generation beneficial microbe, A. soehngenii, was also confirmed to be safe, with no serious adverse events being reported during the study.These results suggest that A. soehngenii could help to delay progression for those with prediabetes and act as a supplement for an otherwise healthy population with elevated levels of glycaemic markers. Further studies would be helpful to support the hypothesis and to add to the existing data on the mechanism of action of A. soehngenii in different cohort groups, with special interest in participants whose baseline characteristics are aligned to the more advanced prediabetic population. The findings from this study will add to the growing body of research in the emerging field of prediabetes and may provide further evidence of the benefits of products based on beneficial endogenous microbes.
REC name
East of Scotland Research Ethics Service REC 2
REC reference
21/ES/0107
Date of REC Opinion
3 Dec 2021
REC opinion
Further Information Favourable Opinion