MR: Plasma Trimethylamine N-oxide Elevation Induced by L-carnitine Supplementation and Insulin Resistance

Sponsor

Poznan University of Physical Education (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT05251207

Collaborator

(none)

Enrollment

Location

Arms

15.7

Anticipated Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary aims of the current study:

using L-carnitine supplementation modulate the level of plasma trimethylamine N-oxide to assess its effect on circulating cytokines related to diabetes and metabolic syndrome;
using simulated night-shift work intervention as a stress factor, explore the effect of circulating metabolites on insulin sensitivity

The secondary aim is to evaluate the effect of carnitine supplementation on gut microbiome composition.

Condition or Disease	Intervention/Treatment	Phase
Insulin Resistance	Dietary Supplement: L-carnitine Dietary Supplement: L-leucine Behavioral: Change of the circadian cycle	N/A

Detailed Description

Subjects will be randomly divided in two groups: supplemented by L-carnitine 2g/day for 12 weeks, and placebo group receiving leucine in identical gelatine capsules.

Subjects who successfully complete the protocol will be divided into four subgroups - two with a changed circadian cycle and two controls (supplemented and placebo). Subgroups with a changed daily cycle will be able to sleep between 8:00 and 17:00 for four consecutive days, while during the night they will stay active in the laboratory. The oral glucose tolerance test (OGTT) will be performed before and after the circadian cycle modification. Glucose levels will be monitored by FreeStyle Libre Sensor. Moreover, the activity of the participants will be monitored by wearable activity trackers.

Before supplementation, as well as before circadian cycle modification and after finishing the whole experimental procedure, fasting blood samples will be collected for determination of plasma trimethylamine N-oxide (TMAO), trimethylamine (TMA), carnitine (free and acyl derivatives), protein markers of diabetes and inflammation.

Moreover, the stool samples will be collected before and after 12 weeks of supplementation, to determine the composition of the gut microbiome. In addition diet of participants will be monitored.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

The Role of Gut Microbiota Metabolite, Trimethylamine N-oxide, in the Insulin Resistance Development

Actual Study Start Date :

Feb 7, 2022

Anticipated Primary Completion Date :

May 31, 2023

Anticipated Study Completion Date :

May 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: carnitine 2 grams of L-carnitine per day for 12 weeks	Dietary Supplement: L-carnitine L-carnitine-L-tartrate Behavioral: Change of the circadian cycle Reducing sleep at night for four consecutive days (enabling sleep between 8:00 and 17:00)
Placebo Comparator: leucine 2 grams of L-leucine per day for 12 weeks	Dietary Supplement: L-leucine L-leucine Behavioral: Change of the circadian cycle Reducing sleep at night for four consecutive days (enabling sleep between 8:00 and 17:00)
Experimental: modified circadian cycle no sleep at night for four consecutive days (enabling sleep between 8:00 and 17:00).	Dietary Supplement: L-carnitine L-carnitine-L-tartrate Dietary Supplement: L-leucine L-leucine
Active Comparator: normal circadian cycle sleep at night for four consecutive days	Dietary Supplement: L-carnitine L-carnitine-L-tartrate Dietary Supplement: L-leucine L-leucine

Outcome Measures

Primary Outcome Measures

Circulating microbiome metabolites [13 weeks]
Determination of plasma trimethylamine and trimethylamine N-oxide using ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS) method
Circulating carnitine metabolites [13 weeks]
Determination of plasma free, total, and acyl-L-carnitines using ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS) method
Circulating diabetes biomarkers [13 weeks]
insulin, C-peptide, ghrelin, leptin, resistin using enzyme-linked immunosorbent assay
Circulating inflammatory biomarkers [13 weeks]
tumor necrosis factor, C-reactive protein using enzyme-linked immunosorbent assay
Oral Glucose Tolerance Test [1 week]
The subjects will consume 75 g of glucose solution drink within a 5-minute time frame. The glucose level will be continuously monitored with the FreeStyle Libre Sensor.

Secondary Outcome Measures

gut microbiome composition [13 weeks]
16 S rRNA sequencing will be used to analyze the gut microbiome in the stool samples

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

healthy volunteers,
must be able to swallow tablets

Exclusion Criteria:

smokers,
cardiovascular disease
liver disease
kidney disease
gastrointestinal disorders (including stomach ulcers and erosions)
diabetes

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Akademia Wychowania Fizycznego	Poznań		Poland	61-871

Sponsors and Collaborators

Poznan University of Physical Education

Investigators

Principal Investigator: Robert Olek, PhD, Poznan University of Physical Education

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Robert Olek, Principal Investigator, Poznan University of Physical Education

ClinicalTrials.gov Identifier:

NCT05251207

Other Study ID Numbers:

2020/39/O/NZ7/01790

First Posted:

Feb 22, 2022

Last Update Posted:

Mar 28, 2022

Last Verified:

Mar 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Insulin Resistance

Study Results

No Results Posted as of Mar 28, 2022