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

Not Applicable

Active, not recruiting

• Conditions: Insulin Resistance
• Interventions: Dietary Supplement: L-carnitine; Dietary Supplement: L-leucine; Behavioral: Change of the circadian cycle

• Registration Number: NCT05251207
• Lead Sponsor: Poznan University of Physical Education

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.

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 Timeline

• Study Start: 2022-02-07
• Study First Submitted: 2022-02-11
• Study First Submitted QC: 2022-02-11
• Study First Posted: 2022-02-22
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-19
• Last Update Posted: 2025-03-24
• Primary Completion: 2025-05-31
• Study Completion: 2026-05-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
normal circadian cycle	L-carnitine	sleep at night for four consecutive days
leucine	L-leucine	2 grams of L-leucine per day for 12 weeks
leucine	Change of the circadian cycle	2 grams of L-leucine per day for 12 weeks
modified circadian cycle	L-carnitine	no sleep at night for four consecutive days (enabling sleep between 8:00 and 17:00).
carnitine	L-carnitine	2 grams of L-carnitine per day for 12 weeks
modified circadian cycle	L-leucine	no sleep at night for four consecutive days (enabling sleep between 8:00 and 17:00).
carnitine	Change of the circadian cycle	2 grams of L-carnitine per day for 12 weeks
normal circadian cycle	L-leucine	sleep at night for four consecutive days

Primary Outcome Measures

Name	Time	Method
Circulating diabetes biomarkers	13 weeks	insulin, C-peptide, ghrelin, leptin, resistin using enzyme-linked immunosorbent assay
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 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

Name	Time	Method
gut microbiome composition	13 weeks	16 S rRNA sequencing will be used to analyze the gut microbiome in the stool samples

Trial Locations

Locations (1)

Akademia Wychowania Fizycznego; 🇵🇱 Poznań, Poland