History of Changes for Study: NCT01729156

Effects of Metformin on Hepatic FFA Metabolism

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Study Record Versions

Version	Submitted Date	Changes
1	November 13, 2012	None (earliest Version on record)
2	November 26, 2012	Outcome Measures, Study Description and Study Status
3	May 10, 2016	Recruitment Status, Study Status, Contacts/Locations, Arms and Interventions and Study Design
4	May 4, 2017	Recruitment Status, Study Status and Oversight
5	March 9, 2019	Outcome Measures, Study Status, Eligibility and Study Description
6	September 24, 2019	Study Status, Outcome Measures, Document Section and Results

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Study Identification


Unique Protocol ID:	C11palmitatMetformin
Brief Title:	Effects of Metformin on Hepatic FFA Metabolism
Official Title:	Effects of Metformin on Hepatic Free Fatty Acid Metabolism in Patients Diagnosed With Type 2 Diabetes: A C11 PET Study
Secondary IDs:

Study Status


Record Verification:	May 2017
Overall Status:	Completed
Study Start:	January 2013
Primary Completion:	May 5, 2017 [Actual]
Study Completion:	May 5, 2017 [Actual]

First Submitted:	November 13, 2012
First Submitted that Met QC Criteria:	November 13, 2012
First Posted:	November 20, 2012 [Estimate]

Last Update Submitted that Met QC Criteria:	May 4, 2017
Last Update Posted:	May 9, 2017 [Actual]

Sponsor/Collaborators


Sponsor:	Lars Christian Gormsen
Responsible Party:	Sponsor-Investigator Investigator: Lars Christian Gormsen Official Title: Senior Registrar, MD PhD Affiliation: Aarhus University Hospital
Collaborators:

Oversight


U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:	Yes

Study Description

Brief Summary:

Background: Metformin treatment has beneficial effects on both glucose and lipid metabolism. Whereas there is general agreement that the blood glucose lowering effect of metformin results from inhibition of hepatic gluconeogenesis, it is less clear exactly how the drug lowers blood triglyceride concentration. There are indications that it enhances hepatic free fatty acid (FFA) oxidation thus diminishing substrate for reesterification and resecretion as very-low-density-lipoprotein (VLDL) triglycerides (TG). However, the liver is not easily accessible for sampling in humans and data on the clinical effects of metformin in the liver are therefore lacking. This may change due to the increasing use of the positron emission tomography (PET) technique. Using PET isotopes (11C or 18F) coupled to either palmitate or a fatty acid analogue, it is possible to non-invasively measure hepatic fatty acid handling.

Aim: To determine how 3 months metformin treatment (1000 mg twice daily) affects hepatic lipid metabolism in patients with newly diagnosed type 2 diabetes.

Design: Randomized, placebo controlled, double-blind parallel study with patients receiving either metformin or placebo. A control group of BMI and age-matched healthy controls will receive metformin for 3 months.

Hypothesis: Metformin lowers VLDL-TG secretion and circulating triglycerides by increasing hepatic fatty acid oxidation

Detailed Description:

Conditions


Conditions:	Type 2 Diabetes Dyslipidemia
Keywords:	Type 2 diabetes Hepatic fatty acid oxidation Dyslipidemia Metformin

Study Design


Study Type:	Interventional
Primary Purpose:	Basic Science
Study Phase:	Phase 4
Interventional Study Model:	Parallel Assignment
Number of Arms:	3
Masking:	Double (Participant, Investigator)
Allocation:	Randomized
Enrollment:	36 [Actual]

Arms and Interventions

Arms	Assigned Interventions
Healthy controls Healthy controls receiving 1000 mg metformin twice daily for 3 months	Drug: Metformin 1000 mg metformin twice daily in 3 months Other Names: Metformin "Sandoz" 500 mg
Placebo Comparator: Placebo Placebo	Drug: Placebo 2 tablets twice daily in 3 months
Active Comparator: Metformin Metformin "Sandoz", 1000 mg twice daily for 3 months	Drug: Metformin 1000 mg metformin twice daily in 3 months Other Names: Metformin "Sandoz" 500 mg

Outcome Measures


Primary Outcome Measures:
1.	Hepatic fatty acid oxidation [ Time Frame: 06/01/2015 ] Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET
2.	Hepatic fatty acid reesterification [ Time Frame: 06/01/2015 ] Hepatic fatty acid reesterification assessed by C11-palmitate PET
3.	Hepatic fatty acid uptake [ Time Frame: 06/01/2015 ] Hepatic fatty acid uptake assessed by C11-palmitate PET
4.	VLDL-TG secretion [ Time Frame: 06/01/2015 ] Hepatic VLDL-TG secretion assessed by [1-14C] VLDL tracer
Secondary Outcome Measures:
1.	Weight loss [ Time Frame: 06/01/2015 ] Weight loss after metformin treatment
2.	Fatty acid turnover [ Time Frame: 06/01/2015 ] Fatty acid turnover assessed as whole body C11-palmitate turnover
3.	VLDL-TG oxidation [ Time Frame: 06/01/2015 ] VLDL-TG oxidation assessed by 14C carbon dioxide (CO2) in exhaled breath

Eligibility


Minimum Age:	50 Years
Maximum Age:	70 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	Yes
Criteria:	Inclusion Criteria: Newly diagnosed type 2 diabetes (>3 and <12 months) Age 50-70 years BMI<40 Exclusion Criteria: Metformin treatment >6 months NASH (non alcoholic steatohepatitis) Cancer Anemia HbA1C>8.5 % Chronic or acute pancreatitis Alcohol or medicine abuse Allergy towards metformin Claustrophobia Severe obesity (weight >130 kilogram)

Contacts/Locations


Study Officials:	Lars C Gormsen, MD PhD Principal Investigator Aarhus University Hospital
Locations:

IPDSharing


Plan to Share IPD:

References


Links:
Available IPD/Information: