Dapagliflozin on Hyperlipidemia and Insulin Resistance in Type 2 Diabetic Patients (DAPHNIS Study)

NCT02577159 | Unknown Phase 4 DMC

• 1 other identifier: DAPHNIS
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

The investigators will investigate whether dapagliflozin (FORXIGA) might improve lipoprotein metabolism as well as hyperglycemia in Japanese patients with type II diabetes mellitus whose HbA1c levels are less than 7.0% (from 20 to 65 years of age). The investigators will examine changes of fasting lipoprotein profile including TG, TC, HDL-C, apoB-48 and RemL-C before and after the 8 weeks administration of dapagliflozin.

Conditions

Diabetes Mellitus, Type 2

Keywords

sodium-glucose cotransporter 2 inhibitor; Diabetes Mellitus, Type 2; dyslipidemia; remnants; apolipoprotein B-48

Outcome Measures

Primary Outcomes (1)

• Changes in fasting lipoprotein profiles

  Changes in fasting lipoprotein profiles including concentrations of apoA-1, apoA-2, apoB, apoB-48, apoC-2, apoC-3, apoE, RemL-C, free-fatty acids profile, LPL protein mass and lipoprotein profile assessed by the HPLC at four and eight weeks after the administration of dapagliflozin

  at four and eight weeks after the administration of dapagliflozin

Secondary Outcomes (5)

• Changes in fasting lipid profiles

  at four and eight weeks after the administration of dapagliflozin

• Changes in fasting blood glucose and HbA1c

  at four and eight weeks after the administration of dapagliflozin

• Changes in insulin and adiponectin

  at four and eight weeks after the administration of dapagliflozin

• Frequency of adverse side effects

  at four and eight weeks after the administration of dapagliflozin

• Changes in biomarkers for renal and hepatic function

  four and eight weeks after the administration of dapagliflozin.

Study Arms (1)

Dapagliflozin

EXPERIMENTAL

Diabetic patients who met the inclusion/exclusion criteria. Dapagliflozin is orally administered for 8 weeks in the dose of 5mg per day if there is no serious event included in termination criteria. If the effect for improving diabetes is insufficient, it is allowed to raise its dose up to 10mg/day.

Drug: Dapagliflozin

Interventions

Dapagliflozin DRUG

Dapagliflozin is orally administered for 8 weeks in the dose of 5mg per day by adding the conventional treatment if there is no serious event included in termination criteria. If the effect for improving diabetes is insufficient, it is allowed to raise its dose up to 10mg/day.

Also known as: conventional treatment

Dapagliflozin

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects with type 2 diabetes mellitus of from 20 to 65 years of age.
• Patients who have not achieve the clinical target of the glycemic control (less than 7.0% in HbA1c).
• Patients who received the diet therapy, the exercise therapy or the following anti-diabetic drugs in addition to the diet and/or exercise therapy (up to two drugs) with dosage stable for 8 weeks prior to entry.
• Sulfonylurea (Glymepiride 2mg/day or less, Glibenclamide 1.25mg/day or less, Gliclazide 40mg/day or less)
• Thiazolidine (Actos)
• Biguanide (Metformin, Buformin)
• alpha-glucosidase inhibitor (Voglibose, Miglitol, Acarbose)
• DPP4 inhibitors (Sitagliptin, Linagliptin, Anagliptin, Teneligliptin, Alogliptin, Saxagliptin)
• Informed consent to participate in the study prior to any study procedures.

You may not qualify if:

• Type 1 diabetes mellitus
• Moderate or severe renal dysfunction (eGFR\<45 ml/min/1.73m2 or hemodialysis)
• Severe hepatic insufficiency (AST and/or ALT \>3x upper limit of normal)
• Adrenal insufficiency or pituitary gland dysfunction
• Malnourishment, starvation, irregular dietary intake, poor dietary intake, debilitating condition or a severe muscle movement
• Volume depleted patients; concomitant medication such as loop diuretics.
• Excessive alcohol intake (\>60g daily)
• SGLT2 inhibitors such as dapagliflozin are already administered
• Contraindication with dapagliflozin
• Start a new medication of statins, fibrates, ezetimibe or probucol within a month
• Females who are likely to be pregnant, during pregnancy or lactating
• Participants in other clinical trials
• Inability to communicate and comply with all study requirements.

Sponsors & Collaborators

• Osaka University: lead

Study Sites (3)

Sousei Hospital

Kadoma, Osaka, 5710025, Japan

Location

Osaka Central Hospital

Osaka, Osaka, 5300001, Japan

Location

Osaka University Hospital

Suita, Osaka, 5650871, Japan

Location

Related Publications (9)

• Hanada H, Mugii S, Okubo M, Maeda I, Kuwayama K, Hidaka Y, Kitazume-Taneike R, Yamashita T, Kawase R, Nakaoka H, Inagaki M, Yuasa-Kawase M, Nakatani K, Tsubakio-Yamamoto K, Masuda D, Ohama T, Matsuyama A, Ishigami M, Nishida M, Komuro I, Yamashita S. Establishment of chemiluminescence enzyme immunoassay for apolipoprotein B-48 and its clinical applications for evaluation of impaired chylomicron remnant metabolism. Clin Chim Acta. 2012 Jan 18;413(1-2):160-5. doi: 10.1016/j.cca.2011.09.013. Epub 2011 Sep 19.

  PMID: 21958700 BACKGROUND

• Masuda D, Sakai N, Sugimoto T, Kitazume-Taneike R, Yamashita T, Kawase R, Nakaoka H, Inagaki M, Nakatani K, Yuasa-Kawase M, Tsubakio-Yamamoto K, Ohama T, Nakagawa-Toyama Y, Nishida M, Ishigami M, Masuda Y, Matsuyama A, Komuro I, Yamashita S. Fasting serum apolipoprotein B-48 can be a marker of postprandial hyperlipidemia. J Atheroscler Thromb. 2011;18(12):1062-70. doi: 10.5551/jat.10470. Epub 2011 Sep 24.

  PMID: 21946533 BACKGROUND

• Okubo M, Hanada H, Matsui M, Hidaka Y, Masuda D, Sakata Y, Yamashita S. Serum apolipoprotein B-48 concentration is associated with a reduced estimated glomerular filtration rate and increased proteinuria. J Atheroscler Thromb. 2014;21(9):974-82. doi: 10.5551/jat.23309. Epub 2014 Jun 2.

  PMID: 24882621 BACKGROUND

• Mugii S, Hanada H, Okubo M, Masuda D, Takeoka K, Hidaka Y, Ohama T, Matsuyama A, Nakagawa-Toyama Y, Nishida M, Ishigami M, Komuro I, Yamashita S. Thyroid function influences serum apolipoprotein B-48 levels in patients with thyroid disease. J Atheroscler Thromb. 2012;19(10):890-6. doi: 10.5551/jat.12757. Epub 2012 Jul 4.

  PMID: 22786447 BACKGROUND

• Nakatani K, Sugimoto T, Masuda D, Okano R, Oya T, Monden Y, Yamashita T, Kawase R, Nakaoka H, Inagaki M, Yuasa-Kawase M, Tsubakio-Yamamoto K, Ohama T, Nishida M, Ishigami M, Komuro I, Yamashita S. Serum apolipoprotein B-48 levels are correlated with carotid intima-media thickness in subjects with normal serum triglyceride levels. Atherosclerosis. 2011 Sep;218(1):226-32. doi: 10.1016/j.atherosclerosis.2011.05.009. Epub 2011 May 18.

  PMID: 21641598 BACKGROUND

• Masuda D, Sugimoto T, Tsujii K, Inagaki M, Nakatani K, Yuasa-Kawase M, Tsubakio-Yamamoto K, Ohama T, Nishida M, Ishigami M, Kawamoto T, Matsuyama A, Sakai N, Komuro I, Yamashita S. Correlation of fasting serum apolipoprotein B-48 with coronary artery disease prevalence. Eur J Clin Invest. 2012 Sep;42(9):992-9. doi: 10.1111/j.1365-2362.2012.02687.x. Epub 2012 May 15.

  PMID: 22587365 BACKGROUND

• Ji L, Ma J, Li H, Mansfield TA, T'joen CL, Iqbal N, Ptaszynska A, List JF. Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus: a randomized, blinded, prospective phase III study. Clin Ther. 2014 Jan 1;36(1):84-100.e9. doi: 10.1016/j.clinthera.2013.11.002. Epub 2013 Dec 28.

  PMID: 24378206 BACKGROUND

• Kaku K, Maegawa H, Tanizawa Y, Kiyosue A, Ide Y, Tokudome T, Hoshino Y, Yang J, Langkilde AM. Dapagliflozin as monotherapy or combination therapy in Japanese patients with type 2 diabetes: an open-label study. Diabetes Ther. 2014 Dec;5(2):415-33. doi: 10.1007/s13300-014-0086-7. Epub 2014 Oct 24.

  PMID: 25341477 BACKGROUND

• Bolinder J, Ljunggren O, Kullberg J, Johansson L, Wilding J, Langkilde AM, Sugg J, Parikh S. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012 Mar;97(3):1020-31. doi: 10.1210/jc.2011-2260. Epub 2012 Jan 11.

  PMID: 22238392 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Dyslipidemias

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Lipid Metabolism Disorders

Study Officials

• Shizuya Yamashita, MD, PhD

  Osaka University Graduate School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2015
• First Posted: October 16, 2015
• Study Start: July 1, 2015
• Primary Completion: December 31, 2017
• Study Completion: August 31, 2018
• Last Updated: August 29, 2018

Record last verified: 2018-01

Locations

JP (3)