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

Insulin Resistance Clinical Trial

— MR  

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05251207
• Other study ID #: 2020/39/O/NZ7/01790
• Status: Suspended
• Phase: N/A
• Start date: February 7, 2022
• Est. completion date: May 31, 2024

Study information

• Verified date: November 2023
• Source: Poznan University of Physical Education
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 60
• Est. completion date: May 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Insulin Resistance

Intervention

Dietary Supplement:
• L-carnitine
L-carnitine-L-tartrate
• 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)

Locations

Country	Name	City	State
Poland	Akademia Wychowania Fizycznego	Poznan

Sponsors (1)

Lead Sponsor	Collaborator
Poznan University of Physical Education

Country where clinical trial is conducted

Poland, 

References & Publications (2)

Bescos R, Boden MJ, Jackson ML, Trewin AJ, Marin EC, Levinger I, Garnham A, Hiam DS, Falcao-Tebas F, Conte F, Owens JA, Kennaway DJ, McConell GK. Four days of simulated shift work reduces insulin sensitivity in humans. Acta Physiol (Oxf). 2018 Jun;223(2):e13039. doi: 10.1111/apha.13039. Epub 2018 Feb 12. — View Citation

Samulak JJ, Sawicka AK, Hartmane D, Grinberga S, Pugovics O, Lysiak-Szydlowska W, Olek RA. L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women. Ann Nutr Metab. 2019;74(1):11-17. doi: 10.1159/000495037. Epub 2018 Nov 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Circulating microbiome metabolites	Determination of plasma trimethylamine and trimethylamine N-oxide using ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS) method	13 weeks
Primary	Circulating carnitine metabolites	Determination of plasma free, total, and acyl-L-carnitines using ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS) method	13 weeks
Primary	Circulating diabetes biomarkers	insulin, C-peptide, ghrelin, leptin, resistin using enzyme-linked immunosorbent assay	13 weeks
Primary	Circulating inflammatory biomarkers	tumor necrosis factor, C-reactive protein using enzyme-linked immunosorbent assay	13 weeks
Primary	Oral Glucose Tolerance Test	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.	1 week
Secondary	gut microbiome composition	16 S rRNA sequencing will be used to analyze the gut microbiome in the stool samples	13 weeks