Healthy Male Adults
Conditions
Keywords
Metabolism, Duodenal infusion, Postbiotics, Gut bacterial peptide, Intervention study, Intestinal infusion, Ruminococcus torques, Plasma glucose, Plasma insulin, Plasma PYY, Plasma incretins, Plasma GIP, Plasma RUCILP, Plasma GLP-1
Brief summary
The goal of this randomized, double-blinded and placebo-controlled clinical cross-over trial is in healthy men to explore the potential metabolic effects of the naturally occurring gut bacterial polypeptide, RUCILP. This bacterial peptide is produced by commensal strains of Ruminococcus torques in the human gut microbiota. In preclinical studies of rodents, RUCILP lowers blood glucose and stimulates release of plasma insulin, glucagon-like peptide-1(GLP-1) and Peptide YY (PYY) but induces a decline of glucose-dependent insulinotropic polypeptide (GIP). In the present trial, the investigators want to explore potential effects of intraduodenally delivered RUCILP on release of plasma concentrations of GLP-1, GIP and PYY. In addition, the investigators will test for potential effects of intestinal RUCILP infusion on plasma concentrations of glucose, insulin and metabolome. Participants will have a duodenal tube placed into which RUCILP or placebo will be infused over 3 hours after an initial standardized liquid meal infusion into the duodenal tube. Participants will on different days and in a randomized order receive either placebo or RUCILP infusion into the tube. Safety is acutely monitored under the intervention and postintervention safety is monitored by clinical biochemistry measures of hematology, and liver and kidney functions. The study participants will further keep a diary of any experienced adverse effects during the week after the intervention. Primary OUTCOMES: a composite of changes in plasma concentrations of GLP-1, GIP and PYY. Secondary OUTCOMES: changes in plasma glucose, plasma insulin and plasma metabolome profile.
Interventions
BIOLOGICALTest bacterial peptide: RUCILP
The naturally occuring gut peptide RUCILP synthesized by the commensal gut bacterium Ruminococcus torques
OTHERPlacebo
Placebo is identical to the active intervention except for the absence of the RUCILP molecule.
Sponsors
Oluf Pedersen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 18 and 35 years * Self-reported good health * Caucasian * Normal body mass index (18.5 to \<25)
Exclusion criteria
* Any known disorder/disease that could interfere with study results or is seen as compromising to the study (as assessed by the investigator), for example diabetes, cancer or cardiovascular or kidney disease. * Use of any daily medication as well as p.r.n. (pro re nata; not taken regularly) medication that cannot be discontinued during the trial * Use of antibiotics during the recent three months * Acute or chronic gastrointestinal symptoms * Lactose intolerance * Smoking * Alcohol or drug abuse * Use of creatine as dietary supplement during study period * Plasma creatinine concentration above the normal range (\>105 μmol/L) * Known significant liver disease or plasma ALAT concentration ≥ 3 × normal value * Values for hemoglobin, leukocytes, or thrombocytes outside of the normal ranges
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentrations of GIP | During the 3 hours of RUCILP/placebo infusion | Plasma measurements of GIP at different time points during the study day. |
| Plasma concentrations of GLP-1 | During the 3 hours of RUCILP/placebo infusion | Plasma measurements of GLP-1 at different time points during the study day. |
| Plasma concentrations of PYY | During the 3 hours of RUCILP/placebo infusion | Plasma measurements of PYY at different time points during the study day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentrations of insulin | During the 3 hours of RUCILP/placebo infusion | Plasma measurements of insulin at different time points during the study day. |
| Plasma concentrations of RUCILP | During the 3 hours of RUCILP/placebo infusion | Plasma measurements of RUCILP at different time points during the study day. |
| Plasma concentrations of glucose | During the 3 hours of RUCILP/placebo infusion | Plasma measurements of glucose at different time points during the study day. |
| Plasma metabolome profile | During the 3 hours of RUCILP/placebo infusion | Plasma metabolome profile at different time points during the study day. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Blood hemoglobin | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of hemoglobin in blood |
| Plasma alanine transaminase (ALT) | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of alanine transaminase (ALT) in plasma |
| Plasma aspartate transferase (AST) | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of aspartate transferase (AST) in plasma |
| Plasma alkaline phosphatase | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of alkaline phosphatase in plasma |
| Plasma albumin | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of albumin in plasma |
| Plasma creatinine | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of creatinine in plasma |
| Experienced adverse effects post infusion | At 180 minutes. | Number of experienced adverse effects as noted in a diary at end of each study day. |
| Plasma sodium | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of sodium in plasma |
| Plasma potassium | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of potassium in plasma |
| Plasma calcium (total) | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of total calcium in plasma |
| Plasma phosphate | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of phosphate in plasma |
| Plasma creatine kinase | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of creatine kinase in plasma |
| Plasma C-reactive protein | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of C-reactive protein in plasma |
| Estimated Glomerular Filtration Rate (eGFR) | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | — |
| Experienced adverse effects during the four days following an infusion | During four days of follow-up after each study day. | Number of experienced adverse effects as noted in a diary during four days of follow-up after each infusion. |
| Blood leukocytes | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of leukocytes in blood |
| Blood eosinophils | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of eosinophils in blood |
| Total blood leukocytes | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of total leukocytes in blood |
| Blood neutrophils | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of neutrophils in blood |
| Blood platelets | At baseline, at 180 minutes, and at follow-up (4-8 days after study day) | Concentration of platelets in blood |
Countries
Denmark
Outcome results
None listed