Effects of Carnitine Supplementation on Liver and Muscle

Study Overview
=================
Brief Summary
-----------------
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.

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

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

Conditions
-----------------
Non-Alcoholic Fatty Liver Disease, Insulin Resistance

Intervention / Treatment
-----------------
* Dietary Supplement: L-Carnitine tartrate
* Dietary Supplement: Meal Replacement Drink
* Dietary Supplement: Maltodextrin


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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 |