UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Effect of EPA/DHA combination therapy on LDL particle size in patients with hyperlipidemia and type 2 diabetes taking HMG-CoA reductive enzyme inhibitors and DPP-4 inhibitors.
Title of the study (Brief title)	Effect of EPA/DHA combination therapy on LDL particle size
Region	Japan

Condition
Condition	Type 2 diabetes mellitus with hyperlipidemia
Classification by specialty	Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	The aim of this study is evaluate the effect of EPA/DHA combination therapy on LDL particle size in patients with hyperlipidemia and type 2 diabetes taking HMG-CoA reductive enzyme inhibitors and DPP-4 inhibitors. It is conducted to the substantial patients from the multi centered participation.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	The change of parameters in LDL particle size (for 12 weeks with administration of EPA/DHA)
Key secondary outcomes	The change of - LDL particle concentration - LDL particle number - Cholesterol and triglyceride concentration, free glycerol concentration - Other cholesterol and triglyceride particle sizes - Other cholesterol and triglyceride particle concentration - Other cholesterol and triglyceride particle number - Lipoprotein Insulin Resistance Score (LPIR) - Inflammation Marker (GlycA) - EPA/AA ratio, DHA/AA ratio - Lipid profile (LDL-C, HDL-C, TG, etc) - HbA1c - Fasting blood glucose - Safety assessment (Renal function, Liver function, etc)

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	EPA/DHA formulation (1) Brand name : Lotriga granulated capsule 2g (2) Generic name : Omega-3 fatty acids ethyl
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	80 years-old >
Gender	Male and Female
Key inclusion criteria	1) Type 2 diabetes mellitus patients, those who received both DPP IV inhibitors and HMG-CoA inhibitors, and have HbA1c level of < 8.0% (NGSP) and LDL-C level of < 120mg/dl. 2) Patients have fasting TG level of >=150mg/dl, those who received diet and exercise therapy more than 12 weeks, and clinically determined to have an additional pharmacotherapy. 3) Patients aged from 20 to 80 years at the baseline 4) Patients provided written informed consent
Key exclusion criteria	Among the patients, those who judged as the criteria below are not eligible for the trial. 1) TG>=1000mg/dl or HDL-C =<30mg/dl 2) Received Fibrates 3) Received Pioglitazone 4) 0mega-3 fatty acids contraindication status (Bleeding: Hemophilia, Peptic ulcer, etc) 5) Hypersensitive history to EPA formulation or EPA/DHA formulation 6) Familial combined hyper low-density lipoproteinaemia 7) Type 1 diabetes mellitus 8) Severe diabetic ketosis, diabetic coma or total coma within 6 months 9) Severe infectious disease, before or after surgery, and sever trauma 10) Moderate renal dysfunction (Serum creatinine (mg/dl): male, 1.5=<; female, 1.3=<) 11) Occurrence of stroke, AMI, and the other severe cardiovascular events that lead patients to be hospitalized within 6 months 12) Concomitant malignant disease 13) Pregnant, lactating, possibly pregnant or planning to become pregnant women 14) Without written informed consent 15) Patients considered as inadequate by the principal investigator
Target sample size	20

Research contact person
Name of lead principal investigator	Masaya Koshizaka
Organization	Chiba University Hospital
Division name	Diabetes, Metabolism and Endocrinology
Address	1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, JAPAN
TEL	043-222-7171
Email	overslope@chiba-u.jp

Public contact
Name of contact person	Masaya Koshizaka
Organization	Chiba University Hospital
Division name	Diabetes, Metabolism and Endocrinology
Address	1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, JAPAN
TEL	043-222-7171
Homepage URL
Email	overslope@chiba-u.jp

Sponsor
Institute	Chiba University Hospital, Division of Diabetes, Metabolism and Endocrinology
Institute
Department

Funding Source
Organization	None
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2014 Year 04 Month 21 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 11 Month 18 Day
Anticipated trial start date	2013 Year 11 Month 20 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	https://lipidworld.biomedcentral.com/track/pdf/10.1186/s12944-018-0706-8?site=lipidworld.biomedcentr
Results	Concentrations of total cholesterol (P？<？0.001), LDL-C (P？= 0.003), and triglyceride (P？<？0.001) decreased following n-3 PUFA administration. N-3 PUFAs decreased the size of very low-density lipoprotein (VLDL; P？<？0.001) particles, but did not affect LDL or high-density lipoprotein (HDL) particles. The concentration of large LDL increased, whereas small LDL decreased, causing the large to small LDL ratio to increase significantly (P？=？0.042). Large VLDL and chylomicron concentrations significantly decreased, as did the large to small VLDL ratio (all P？<？0.001). FPG levels unchanged, whereas HbA1c levels slightly increased. LPIR scores improved significantly (P？= 0.001).
Other related information

Management information
Registered date	2014 Year 04 Month 21 Day
Last modified on	2018 Year 03 Month 17 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016078