Kinetics of Metabolic Cofactors in NAFLD

NCT03838822 | Completed Early Phase 1

• 1 other identifier: Cofactor Calibration 1.0
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Healthy

Keywords

nicotinamid riboside; L-carnitine; L-serine; N-acetylcystein

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (2)

• Changes in the plasma level of metabolites associated with the supplementation of metabolic co-factors.

  Twenty-four hours after administration of combined cofactors

• 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

Study Arms (1)

Intervention

EXPERIMENTAL

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

Dietary Supplement: Cofactors

Interventions

Cofactors DIETARY_SUPPLEMENT

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

Intervention

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy without any medication, no smokers, no obesity

You may not qualify if:

• Any known disease, obesity

Sponsors & Collaborators

• Sahlgrenska University Hospital: lead
• Karolinska Institutet: collaborator
• Chalmers University of Technology: collaborator

Study Sites (2)

Hanns-Ulrich Marschall

Gothenburg, 411 31, Sweden

Location

Sahlgrenska Academy

Gothenburg, Sweden

Location

MeSH Terms

Interventions

5,11-methenyltetrahydrohomofolate

Study Officials

• Hanns-Ulrich Marschall, Prof

  Sahlgrenska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, University Hospital Consultant

Study Record Dates

• First Submitted: February 4, 2019
• First Posted: February 12, 2019
• Study Start: September 1, 2018
• Primary Completion: November 1, 2018
• Study Completion: December 1, 2018
• Last Updated: February 15, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)