Kinetics of Metabolic Cofactors in NAFLD

Healthy Clinical Trial

— NAFLDCOFCAL  

Official title:

Kinetics of Metabolic Cofactors After Oral Supplementation in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03838822
• Other study ID #: Cofactor Calibration 1.0
• Status: Completed
• Phase: Early Phase 1
• Start date: September 1, 2018
• Est. completion date: December 1, 2018

Study information

• Verified date: February 2019
• Source: Sahlgrenska University Hospital, Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There is a strong correlation between major adverse health consequences of obesity and development of non-alcoholic fatty liver disease (NAFLD). NAFLD is characterized by abnormal hepatic accumulation of triglycerides and other lipids. It has become a worldwide health problem that accelerates cirrhosis, type 2 diabetes mellitus (T2DM), and especially premature cardiovascular morbidity and mortality.

The plasma level of glutathione (GSH) is typically depleted in individuals with metabolism related disorders. However, cellular GSH levels cannot be increased by supplementing GSH and it must be synthesized within the liver either de novo or by salvation pathway. The level of GSH is not enough to maintain and regulate the thiol redox status of the liver in subjects with high hepatic steatosis at fasting stage due to the depletion of glycine. Glycine can be synthesized via the interconversion of serine. It has been shown that the serine synthesis is downregulated in patients with NAFLD and supplementation of serine has attenuated alcoholic fatty liver by enhancing homocysteine metabolism in mice and rats. Depleted liver glutathione is also restored by the administration of N-acetylcystein as in acetaminophen poising. L-carnitine and nicotinamide that both stimulate the transfer of fatty acids from cytosol to mitochondria have been identified as two additional cofactors that are depleted in patients with NAFLD.

In this study, the kinetics in blood of pivotal metabolic cofactors, serine, L-carnitine, N-acetylcystein and nicotinamide after single and simultaneous dietary supplementation, are measured.

Description:

In 10 healthy subjects with BMI <30 kg/m2 the plasma concentrations of 4 natural compounds (nicotinamide riboside, L-carnitine, L-serine and N-acetylcystein) are measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLCMSMS) after individual and combined administration, on five consecutive days and at every hour during 9 hours after administration. The study will start at 8:00 every morning and at each time point, blood samples will be collected.

The taste and any potential sensing of the co-factors such as vertigo, nausea, bowel movement will be recorded.

Each participant will receive one oral dose of Day 1: 1 g nicotinamide riboside; Day 2: 3 g L-carnitine; Day 3: 5 g N-acetylcystein; Day 4: 20 g L-serine; Day 5: combined 1 g nicotinamide riboside, 3 g L-carnitine, 5 g N-acetylcystein, and 20 g L-serine

In addition, untargeted metabolomics analysis as well as O-link proteomics analysis we be performed to study effect of the administered cofactors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 1, 2018
• Est. primary completion date: November 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

Healthy without any medication, no smokers, no obesity

Exclusion Criteria:

Any known disease, obesity

Related Conditions & MeSH terms

• Healthy

Intervention

Dietary Supplement:
• Cofactors
Oral administration of 1g nicotinamide riboside, 3g L-carnitine, 20g serine and 5g N-acetylcystein, first as single compounds, then combined, on 5 days

Locations

Country	Name	City	State
Sweden	Hanns-Ulrich Marschall	Göteborg
Sweden	Sahlgrenska Academy	Göteborg

Sponsors (3)

Lead Sponsor	Collaborator
Sahlgrenska University Hospital, Sweden	Chalmers University of Technology, Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of plasma levels of nicotinamide riboside measured by mass spectrometry	Plasma levels of nicotinamide riboside by UPLCMSMS at 8 time points during 24h after administration	Twenty-four hours after administration
Primary	Changes of plasma levels of L-carnitine measured by mass spectrometry	Plasma levels of L-carnitine (nM) measured by UPLCMSMS at 8 time points during 24h after administration	Twenty-four hours after administration
Primary	Changes of plasma levels of L-serine measured by mass spectrometry	Plasma levels of L-serine (nM) measured by UPLCMSMS at 8 times points during 24h after administration	Twenty-four hours after administration
Primary	Changes of plasma levels of N-acetylcystein measured by mass spectrometry	Plasma levels of N-acetylcystein (nM) measured by UPLCMSMS at 8 times points during 24h after administration	Twenty-four hours after administration
Secondary	Changes in the plasma level of metabolites associated with the supplementation of metabolic co-factors.	Untargeted metabolomic analysis using mass spectrometry. (Untargeted = not pre-specified in terms of outcome)	Twenty-four hours after administration of combined cofactors
Secondary	Changes in the plasma level of inflammation-related proteins associated with the supplementation of metabolic co-factors.	Changes in the plasma level of inflammation related proteins associated with the supplementation of metabolic co-factors.	Twenty-four hours after administration of combined cofactors