Effect of F. Prausnitzii on Glycemic Control

Non-Alcoholic Fatty Liver Disease Clinical Trial

Official title:

Effect of F. Prausnitzii on Glycemic Control - a Randomized, Double Blind, Placebo-controlled Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04938843
• Other study ID #: META003
• Status: Recruiting
• Phase: N/A
• Start date: August 16, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: September 2021
• Source: MetaboGen AB
• Contact: Sara Maclus, PhD
• Phone: +46 705823222
• Email: sara.malcus[@]metabogen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The microbiota is associated with a wide spectrum of diseases including diabetes and non-alcoholic fatty liver disease. In this study we will investigate if the bacteria F. prausnitzii, which is a part of the human gut microbiota, can improve metabolic parameters in subjects with impaired glucose control.

Description:

This is a randomized, double blind, placebo-controlled study. Subjects with impaired glucose control will after signing the informed consent and fulfilling the study criteria be randomized to study product or placebo. The randomization ratio between the study product (F. prausnitzii 1E8-5x1E8 CFU and D. piger) and placebo is 1:1. In total 176 subjects will be randomized in the study.

The study will start with a Run-in period i.e. all the subjects will be given placebo capsules. The subjects fulfilling the inclusion and exclusion criteria will be randomized at Visit 2 to either study product or placebo in the ration 1:1. The treatment will last for 12 weeks, from Visit 2 to Visit 6. The study is ended with a 2-week period of follow up after the final dose.

Blood samples are taken at Visits 1-4 and Visits 6-7. Feces samples are collected at Visit 2-7. One additional fecal sample will be sent by mail approximately one week after Visit 1. Glucose monitoring (CGM) will be initiated at Visit 1 and Visit 5 and followed for 10 days.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 176
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 75 Years

Eligibility

Inclusion Criteria:

• Written informed consent to participate in the study

• Man or woman 50-75 years of age

• Impaired glucose tolerance (IGT; capillary b-glucose 8.9-12.1 mmol/L, 120 minutes after OGTT), impaired fasting glucose (IFG; capillary b-glucose 6.1-6.9 mmol/L) or combined glucose intolerance (CGI, i.e. IFG and IGT)

• Weight stable ±5 kg for the last 3 months, BMI >18 kg/m2

• Willingness and possibility to come to the planned study visits, use the Diary and eQuestionnaires as well as follow the study instructions

• Understand Swedish in speech and writing

Exclusion Criteria:

• Other reasons for liver inflammation e.g. hepatitis A, hepatitis B, hepatitis C, HIV-positive, confirmed or suspected cirrhosis, Wilsons disease, autoimmune hepatitis, hemochromatosis, alcohol related fatty liver or pancreatitis, laboratory screen AST/ALT >2 (ULN), Bilirubin >1 (ULN)

• Heart failure NYHA class III, cardiovascular event within 6 months, unstable angina pectoris

• Diabetes mellitus, HbA1c >47 mmol/mol or fp-Glucose >6.9 mmol/L on 2 occasions

• Chronic obstructive pulmonary disease and asthma treated with intermittent steroids to be under control

• Blood pressure >170/105 mmHg

• Blood donation >500 mL blood <3 months before screening

• Anemia, Hb <117 g/L females and Hb <134 g/L males; leukopenia, LPK <3.5x1E9/L, ongoing infection CRP >10 mg/L

• Hyperthyroidism, T4 >22 nmol/L or hypothyroidism, TSH >4,2 mIU/L

• Laboratory result of clinical significance meaning that participation in the study is unsuitable according to Investigator

• Calculated glomerular filtration rate (GFR) <60 mL/min/1.73 m2

• Cancer <5 years since diagnosis, except for basal-cell carcinoma

• Treatment during the last 3 months with oral steroids, biological drugs, immunosuppressive drugs, e.g. cyklosporin, drugs known to cause liver damage or to be liver toxic

• Bariatric surgery

• Antibiotic treatment during the last 3 months or reoccurring antibiotic treatment >3 times a year

• Regular or sporadic use of probiotic product (not food containing probiotics) during the last 3 months

• Confirmed IBD, irritable bowel syndrome (IBS), bile acid malabsorption, gastrointestinal infections during the last 3 months or any experienced problems from the gastrointestinal tract during the last month that the Investigator expect could influence the participation in the study

• Allergy to metronidazol, the adhesive glue for the CGM sensor, milk protein

• Smoking >10 cigarettes/day

• Alcohol consumption, >7 units/week females, >14 units/week males

• Use of narcotics e.g. cannabis, amphetamine (not medical use), hallucinogens, gamma-hydroxybutyric acid

• Pregnancy, breast-feeding or planned pregnancy

• Participation in other studies except IGT2

Related Conditions & MeSH terms

• Fatty Liver
• Glucose Intolerance
• Impaired Glucose Tolerance
• Liver Diseases
• Non-Alcoholic Fatty Liver Disease
• Pre Diabetes
• Prediabetic State

Intervention

Dietary Supplement:
• F. prausnitzii and D. piger
Dietary supplementation with capsules containing F. prausnitzii and D. piger once daily for 12 consecutive weeks
• Placebo
Dietary supplementation with placebo capsules identical to those containing F. prausnitzii and D. piger once daily for 12 consecutive weeks

Locations

Country	Name	City	State
Sweden	Wallenberg Laboratory, University of Gothenburg	Gothenburg	Västra Götaland

Sponsors (2)

Lead Sponsor	Collaborator
MetaboGen AB	Göteborg University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemic control	Change in time (%) glucose concentration range of 3.5-6.0 mmol/L measured with continuous glucose monitoring (CGM)	From baseline to week 12
Secondary	Fasting plasma glucose levels	Change in fp-glucose	From baseline to week 12
Secondary	Hemoglobin A1c	Change in b-HbA1c	From baseline to week 12
Secondary	Homeostatic Model Assessment (HOMA) for Insulin Resistance (IR)	Change in HOMA-IR	From baseline to week 12
Secondary	Continuous glucose monitoring (CGM) mean	Change in CGM mean	From baseline to week 12
Secondary	CGM SD	Change in CGM SD	From baseline to week 12
Secondary	CGM CV	Change in CGM CV	From baseline to week 12
Secondary	CGM MAGE	Change in CGM MAGE	From baseline to week 12
Secondary	Glucose levels	Change in CGM time (%) glucose concentration =7.0 mmol/L	From baseline to week 12
Secondary	Liver fat content	Change in liver fat measured by transient elastography and given as CAP (continous attenuation parameter) in db/m	From baseline to week 12
Secondary	Liver fat content	Change in liver fat measured by ultrasound (kPa)	From baseline to week 12
Secondary	Liver fat function test AST	Change in AST	From baseline to week 12
Secondary	Liver fat function test ALT	Change in ALT	From baseline to week 12
Secondary	Liver fat function test GGT	Change in GGT	From baseline to week 12