Clinical trial NCT05251207: Plasma Trimethylamine N-oxide Elevation Induced by L-carnitine Supplementation and Insulin Resistance
Official title: The Role of Gut Microbiota Metabolite, Trimethylamine N-oxide, in the Insulin Resistance Development
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Insulin Resistance
Lead sponsor: Poznan University of Physical Education
Sponsor class: OTHER
First posted: 2022-02-22
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Circulating microbiome metabolites
timeFrame: 13 weeks
measure: Circulating carnitine metabolites
timeFrame: 13 weeks
measure: Circulating diabetes biomarkers
timeFrame: 13 weeks
measure: Circulating inflammatory biomarkers
timeFrame: 13 weeks
measure: Oral Glucose Tolerance Test
timeFrame: 1 week
Secondary outcomes:
measure: gut microbiome composition
timeFrame: 13 weeks
Other outcomes:
Locations:
city: Poznań
country: Poland
facility: Akademia Wychowania Fizycznego
Study officials:
affiliation: Poznan University of Physical Education
name: Robert Olek, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.