Effects of Carnitine Supplementation on Liver and Muscle (ECLIPSE)

Effect of Carnitine Supplementation on Liver Steatosis, Insulin Sensitivity, Plasma Glucose Homeostasis, Skeletal Muscle Metabolism and Energetics: a Pilot Study

It will be evaluated whether carnitine, a dietary supplement, reduces liver fat and improves metabolism in individuals who have a high concentration of fat within their liver. Participants will be given either Carnitine or placebo, together with a meal replacement milkshake twice daily for 6 months.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: L-Carnitine tartrate; Dietary supplement: Meal Replacement Drink; Dietary supplement: Maltodextrin

Detailed Description

NAFLD occurs when too much fat accumulates in liver tissue. This can, over time, cause inflammation and scarring of the liver, eventually leading to chronic liver disease and cirrhosis. It is strongly associated with diabetes and obesity, both of which are endemic in Western societies.

Carnitine enables cells in the body to use fat as a fuel, and recent studies have suggested that carnitine supplementation may reduce liver triglyceride content. Muscle and liver are the major sites in the body which coordinate glucose and fat metabolism. As well as assessing the effect of carnitine supplementation on liver fat, its effect on metabolic processes within these tissues will also be measured

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Notts
    • Nottingham, Notts, United Kingdom, NG72UH
      • David Greenfield Human Physiology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Elevated liver fat on screening abdominal ultrasound
• Capable of providing informed consent
• Non-vegetarian diet
• BMI <40 kg/m2
• Weekly ethanol consumption <21 units/week
• Negative non-invasive liver screen, including Hepatitis B and C serology, liver autoantibodies, transferrin saturation, α1-antitrypsin levels.

Exclusion Criteria:

• Known history of cardiovascular disease
• Known diabetes mellitus
• Known psychiatric comorbidity
• Chronic kidney disease
• Surgery within 6 months prior to start of study
• Exposure to drugs known to influence hepatic steatosis (including steroids, statins, omega-3-fatty acids)
• Current smokers
• Contraindications to magnetic resonance scanning, including implanted ferrous material (implantable pacemakers or defibrillators), metallic ocular foreign bodies, ferromagnetic aneurysm clips or severe claustrophobia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carnitine and Meal Replacement Drink; 2g L-carnitine tartrate consumed with a meal replacement milkshake (Slimfast, UK) twice a day for 24 weeks.	Dietary supplement: L-Carnitine tartrate; 2g L-Carnitine tartrate as a powder consumed twice a day; Dietary supplement: Meal Replacement Drink; 325ml dairy-based meal replacement drink ('Slimfast' trademark of KSF Acquisition UK Ltd) consumed twice a day; Other Names: Slimfast
Placebo Comparator: Placebo and Meal Replacement Drink; 2g Maltodextrin consumed with a meal replacement milkshake (Slimfast, UK) twice a day for 24 weeks.	Dietary supplement: Meal Replacement Drink; 325ml dairy-based meal replacement drink ('Slimfast' trademark of KSF Acquisition UK Ltd) consumed twice a day; Other Names: Slimfast; Dietary supplement: Maltodextrin; 2g Maltodextrin powder packaged to mimic carnitine powder consumed twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intrahepatic triglyceride (IHTG) content	IHTG measured by proton magnetic resonance spectroscopy	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
liver sensitivity to insulin	suppression of glucose output from the liver during a 20 mU.m-2.min-1 hyperinsulinaemic euglycaemic clamp	24 weeks
whole body insulin sensitivity	whole body glucose uptake during a 50 mU.m-2.min-1 hyperinsulinaemic euglycaemic clamp	24 weeks
Muscle lipid content	lipid content of the vastus lateralis muscle measured by proton magnetic resonance spectroscopy	24 weeks
Skeletal muscle sensitivity to insulin	Arterialised-venous vs. femoral venous difference in blood glucose concentration during the last hour of a 2 hour 50 mU.m-2.min-1 hyperinsulinaemic euglycaemic clamp	24 weeks
whole body composition	Fat and lean tissue mass assessment by dual energy X-ray absorptiometry	24 weeks
Liver energy metabolism	hepatic ATP flux assessed by 31-phosphorous magnetic resonance spectroscopy	24 weeks

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Nottingham University Hospitals NHS Trust; National Institute for Health Research, United Kingdom
• Investigators: Principal Investigator: Guru Aithal, MD, PhD, University of Nottingham

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2018
• Primary Completion (Actual): August 30, 2020
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: February 14, 2018
• First Submitted That Met QC Criteria: February 14, 2018
• First Posted (Actual): February 20, 2018

Study Record Updates

• Last Update Posted (Actual): November 30, 2021
• Last Update Submitted That Met QC Criteria: November 29, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Liver Diseases; Fatty Liver; Insulin Resistance; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 17086; 17/EM/0441 (Other Identifier: REC Reference)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No