Clinical trial NCT04938843: Effect of F. Prausnitzii on Glycemic Control
Official title: Effect of F. Prausnitzii on Glycemic Control - a Randomized, Double Blind, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pre Diabetes
Impaired Glucose Tolerance
Non-Alcoholic Fatty Liver Disease
Keywords: Faecalibacterium prausnitzii
Desulfovibrio piger
Lead sponsor: MetaboGen AB
Sponsor class: INDUSTRY
Collaborators: name: Göteborg University
First posted: 2021-06-24
Enrollment: 176
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Glycemic control
timeFrame: From baseline to week 12
Secondary outcomes:
measure: Fasting plasma glucose levels
timeFrame: From baseline to week 12
measure: Hemoglobin A1c
timeFrame: From baseline to week 12
measure: Homeostatic Model Assessment (HOMA) for Insulin Resistance (IR)
timeFrame: From baseline to week 12
measure: Continuous glucose monitoring (CGM) mean
timeFrame: From baseline to week 12
measure: CGM SD
timeFrame: From baseline to week 12
measure: CGM CV
timeFrame: From baseline to week 12
measure: CGM MAGE
timeFrame: From baseline to week 12
measure: Glucose levels
timeFrame: From baseline to week 12
measure: Liver fat content
timeFrame: From baseline to week 12
measure: Liver fat content
timeFrame: From baseline to week 12
measure: Liver fat function test AST
timeFrame: From baseline to week 12
measure: Liver fat function test ALT
timeFrame: From baseline to week 12
measure: Liver fat function test GGT
timeFrame: From baseline to week 12
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Wallenberg Laboratory, University of Gothenburg
state: Västra Götaland
Study officials:
affiliation: Wallenberg Laborotory, University of Gothenburg
name: Hanns-Ulrich Marschall
role: PRINCIPAL_INVESTIGATOR
References: