Effect of 4 Weeks of Oral D. Piger on Safety, Pharmacokinetics and Ethanol Metabolism in Overweight Individuals (2023) (PIGER)

The goal of the study is to determine the effect of supplementation of the d piger strain on intestinal ethanol production in individuals with overweight.

The investigators will perform a randomized trial in 2x10 participants to measure effects on ethanol in blood, and perform fecal analyses.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Metabolic Syndrome; Steatosis of Liver
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: D piger

Detailed Description

The investigators perform a randomized, placebo controlled trial in 2x10 participants.

The participants will be given placebo or d piger as an oral suspension once daily for 30 days.

At baseline and after 30 days, a fructose challenge test with fomepizole, gastroduodenoscopy and MRI liver + FibroScan will be performed. Patient will attend the clinical trial unit weekly for safety visits.

The participants will be overweight males or females age 18-70 with impaired glucose tolerance.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: M Nieuwdorp, prof dr; Phone Number: 020-5669111; Email: m.nieuwdorp@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam UMC location AMC
    • Contact: max nieuwdorp, MD PhD; Phone Number: 0031 20 5669111; Email: m.nieuwdorp@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion:

Male or (postmenopausal) females

• Increased waist circumference (>102 cm men, 88>cm women)
• Insulin resistance (HOMA>2.5)
• 18-70 years

Exclusion Criteria:

• Use of systemic medication (except for paracetamol), including antibiotics and pro-/prebiotics in the past three months or during the study period.
• A history of a cardiovascular event
• A history of cholecystectomy
• Overt untreated gastrointestinal disease or abnormal bowel habits
• Liver enzymes>2.5 fold higher than the upper limit of normal range
• Smoking
• Alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo vial (10ml of glycerol 10% and 10% maltrodextrin)	Dietary supplement: Placebo; Placebo
Experimental: D piger; D. piger vial with 109 colony forming units (CFU) (=108 CFU D. piger per ml in 10ml of glycerol 10% and 10% maltrodextrin).	Dietary supplement: D piger; Probiotic d piger

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut engraftment	the number of reads of d piger in feces using q pcr	30 days
adverse events	the number of adverse events in both groups	30 days
Renal function	Number of participants with a decreased kidney function, defined as a rise in serum creatinine of >26,5 micromol/L in 48 h	30 days
Occurence of anemia	Number of patients with Hb < 8,5 mmol/L	30 days
Changes in leucocytes	Number of patients with leucocytes <4,0 or >10,5 x10E9 cells/L	30 days
Changes in thrombocytes	Number of patients with thrombocytes <150 x 10E9 cells/	30 days
Changes in aspartate aminotransferase (AST)	Number of patients with AST > 43 IU/L	30 days
Changes in alanine aminotransferase (ALT)	Number of patients with ALT > 45 IU/L	30 days
Changes in alkaline phosphatase (ALP)	Number of patients with ALP > 126 IU/L	30 days
Changes in Gamma-glutamyltransferase (GGT)	Number of patients with GGT > 117 IU/L	30 days
Changes in total bilirubin	Number of patients with total bilirubin > 24 micromol/L	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fructose in peripheral blood	Area under the curve of fructose in peripheral blood upon ingestion of 1 gram / kg unlabeled fructose in combination with 1000mg of D-fructose-13C6	30 days
Fructose metabolites in breath	Area under the curve of various metabolites (e.g. ethanol) will be measured in breath samples upon ingestion of 1 gram / kg unlabeled fructose in combination with 1000mg of D-fructose-13C6	30 days
Time-in-range	Increase in Time-in-range (TIR,%), a parameter of continuous glucose monitoring devices, where TIR can be between 0 and 100%. A higher TIR reflects a better outcome.	30 days
Continuous glucose monitoring	Decrease in glucose variability (GV, %), a parameter of continuous glucose monitoring devices, where GV can be between 0 and 100%. A lower GV reflects a better outcome.	30 days
Glycemic control	Changes in fasting glucose (mmol/L)	30 days
Dietary intake	Participants are asked to fill out an online dietary questionnaire for the 3 days prior to study visit 2,3,4,5 and 7	30 days
Questionnaires	Changes in Gastro-intestinal Quality of Life Index (GIQLI score) (points). The minimum and maximum score are 31 and 155 points respectively, and a higher score reflects a better outcome.	30 days
Intestinal microbiota composition	Changes from baseline of relative abundance (%) of bacterial phyla, genera and species between groups and within participants.	30 days
Fructose metabolites in feces	Using 24h feces, the investigators will measure fecal concentrations of fructose metabolites such as ethanol, as well as short chain fatty acids (SCFAs) and bile acids.	30 days
Fructose metabolites in urine	Using 24h urine, the investigators will measure fecal concentrations of fructose metabolites such as ethanol, as well as SCFAs and bile acids.	30 days
Bioreactor analyses	Using specific anaerobic culturing, ethanol production of fecal samples will be assessed of bacterial strains.	30 days
MRI	Liver fat measured by proton density fat fraction (PDFF) MRI liver	30 days
FibroScan	Liver stiffness measured by FibroScan	30 days

Collaborators and Investigators

• Sponsor: Max Nieuwdorp
• Investigators: Principal Investigator: Max Nieuwdorp, prof dr, Amsterdam UMC, location AMC

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: May 20, 2024
• First Submitted That Met QC Criteria: July 15, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): July 16, 2024
• Last Update Submitted That Met QC Criteria: July 15, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Liver Diseases; Overnutrition; Nutrition Disorders; Body Weight; Insulin Resistance; Hyperinsulinism; Fatty Liver; Metabolic Syndrome; Overweight
• Other Study ID Numbers: 2023.0787

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No