Effect of F. Prausnitzii on Glycemic Control

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pre Diabetes, Impaired Glucose Tolerance, Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Dietary Supplement: F. prausnitzii and D. piger
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: F. prausnitzii and D. piger<br>1 capsule administered once daily 45 minutes before breakfast for 12 weeks | Dietary Supplement: F. prausnitzii and D. piger<br>* Dietary supplementation with capsules containing F. prausnitzii and D. piger once daily for 12 consecutive weeks<br>|
| Placebo Comparator: Placebo<br>1 capsule administered once daily 45 minutes before breakfast for 12 weeks | Dietary Supplement: Placebo<br>* Dietary supplementation with placebo capsules identical to those containing F. prausnitzii and D. piger once daily for 12 consecutive weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting plasma glucose levels | Change in fp-glucose | From baseline to week 12 | 
| Hemoglobin A1c | Change in b-HbA1c | From baseline to week 12 | 
| Homeostatic Model Assessment (HOMA) for Insulin Resistance (IR) | Change in HOMA-IR | From baseline to week 12 | 
| Continuous glucose monitoring (CGM) mean | Change in CGM mean | From baseline to week 12 | 
| CGM SD | Change in CGM SD | From baseline to week 12 | 
| CGM CV | Change in CGM CV | From baseline to week 12 | 
| CGM MAGE | Change in CGM MAGE | From baseline to week 12 | 
| Glucose levels | Change in CGM time (%) glucose concentration ≥7.0 mmol/L | From baseline to week 12 | 
| 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 | 
| Liver fat content | Change in liver fat measured by ultrasound (kPa) | From baseline to week 12 | 
| Liver fat function test AST | Change in AST | From baseline to week 12 | 
| Liver fat function test ALT | Change in ALT | From baseline to week 12 | 
| Liver fat function test GGT | Change in GGT | From baseline to week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Faecalibacterium prausnitzii, Desulfovibrio piger