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Kinetics of Metabolic Cofactors in NAFLD (NAFLDCOFCAL)

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ClinicalTrials.gov Identifier: NCT03838822
Recruitment Status : Completed
First Posted : February 12, 2019
Last Update Posted : February 15, 2019
Sponsor:
Collaborators:
Karolinska Institutet
Chalmers University of Technology
Information provided by (Responsible Party):
Hanns-Ulrich Marschall, Sahlgrenska University Hospital, Sweden

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.


Condition or disease Intervention/treatment Phase
Healthy Dietary Supplement: Cofactors Early Phase 1

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Kinetics of Metabolic Cofactors After Oral Supplementation in Healthy Subjects
Actual Study Start Date : September 1, 2018
Actual Primary Completion Date : November 1, 2018
Actual Study Completion Date : December 1, 2018

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




Primary Outcome Measures :
  1. Changes of plasma levels of nicotinamide riboside measured by mass spectrometry [ Time Frame: Twenty-four hours after administration ]
    Plasma levels of nicotinamide riboside by UPLCMSMS at 8 time points during 24h after administration

  2. Changes of plasma levels of L-carnitine measured by mass spectrometry [ Time Frame: Twenty-four hours after administration ]
    Plasma levels of L-carnitine (nM) measured by UPLCMSMS at 8 time points during 24h after administration

  3. Changes of plasma levels of L-serine measured by mass spectrometry [ Time Frame: Twenty-four hours after administration ]
    Plasma levels of L-serine (nM) measured by UPLCMSMS at 8 times points during 24h after administration

  4. Changes of plasma levels of N-acetylcystein measured by mass spectrometry [ Time Frame: Twenty-four hours after administration ]
    Plasma levels of N-acetylcystein (nM) measured by UPLCMSMS at 8 times points during 24h after administration


Secondary Outcome Measures :
  1. Changes in the plasma level of metabolites associated with the supplementation of metabolic co-factors. [ Time Frame: Twenty-four hours after administration of combined cofactors ]
    Untargeted metabolomic analysis using mass spectrometry. (Untargeted = not pre-specified in terms of outcome)

  2. Changes in the plasma level of inflammation-related proteins associated with the supplementation of metabolic co-factors. [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Healthy without any medication, no smokers, no obesity

Exclusion Criteria:

Any known disease, obesity


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03838822


Locations
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Sweden
Hanns-Ulrich Marschall
Göteborg, Sweden, 411 31
Sahlgrenska Academy
Göteborg, Sweden
Sponsors and Collaborators
Sahlgrenska University Hospital, Sweden
Karolinska Institutet
Chalmers University of Technology
Investigators
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Principal Investigator: Hanns-Ulrich Marschall, Prof Sahlgrenska University Hospital, Sweden

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Responsible Party: Hanns-Ulrich Marschall, Professor, University Hospital Consultant, Sahlgrenska University Hospital, Sweden
ClinicalTrials.gov Identifier: NCT03838822     History of Changes
Other Study ID Numbers: Cofactor Calibration 1.0
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hanns-Ulrich Marschall, Sahlgrenska University Hospital, Sweden:
nicotinamid riboside
L-carnitine
L-serine
N-acetylcystein
Additional relevant MeSH terms:
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Tetrahydrofolates
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs