The Effects of Dapagliflozin on HDL Particles Subtypes and Reverse Cholesterol Transport in Type 2 Diabetic Patients

NCT02327039 | Completed Phase 4

• 3 other identifiers: 3302/AO/142014-004270-42ESR-14-10088
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

In Phase 2b/3 clinical trials, Dapagliflozin has been shown to raise HDL cholesterol levels by about 4 mg/dl (1 mmol/l), which is generally considered a clinically-meaningful change. As this HDL cholesterol increase is carried out with concomitant improvement in glucotoxicity and body weight reduction, it is possible that treatment with Dapagliflozin also improves HDL function. This is important because clinical, epidemiological and experimental studies indicate that HDL function may be more important than HDL cholesterol levels in determining the protective cardiovascular effects of HDL particles. In addition, knowing the effects of Dapagliflozin on HDL function can help interpreting the increase in HDL cholesterol levels observed in Dapagliflozin-treated patients. Finally, discovery of extra-glycemic effects of Dapagliflozin will shed new light on the potential benefits of therapy with Dapagliflozin and SGLT2i in general. So far, no study evaluated the effects of Dapagliflozin (or other SGLT2i) on HDL function. The investigators hypothesize that Dapagliflozin, in addition to raising HDL cholesterol levels, also increases HDL functionality, measured as reverse cholesterol transport and anti-oxidant capacity, in patients with T2DM

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Change from baseline in reverse cholesterol transport, measured as cholesterol efflux capacity of patient's plasma

  Detection of a significant change in reverse cholesterol transport by patients' plasma in Dapagliflozin compared to placebo-treated diabetic patients. The cholesterol efflux capacity of patient's plasma will be measured as arbitrary units using radioactive cholesterol loaded macrophages

  12 weeks

Secondary Outcomes (5)

• Changes from baseline in HDL cholesterol levels

  12 weeks

• Changes from baseline in the distribution in HDL subclasses

  12 weeks

• Changes from baseline in HDL antioxidant activity

  12 weeks

• Changes from baseline in CETP activity

  12 weeks

• Safety as measured by monitoring of adverse events

  12 weeks

Other Outcomes (3)

• Exploratory analyses - changes from baseline in plasma cytokines

  12 weeks

• Exploratory analyses - changes from baseline in plasma bioimpedance body composition

  12 weeks

• Exploratory analyses - changes from baseline in impedance cardiography analysis

  12 weeks

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin 10 mg tablet once daily for 12 weeks

Drug: Dapagliflozin

Placebo

PLACEBO COMPARATOR

Placebo 10 mg tablet once daily for 12 weeks

Drug: Placebo

Interventions

Dapagliflozin DRUG

Sodium glucose cotransporter-2 inhibitor

Also known as: Forxiga

Dapagliflozin

Placebo DRUG

Tables of Dapagliflozin placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Female and male subjects aged 18-75 years
• Type 2 diabetes on oral agents +/- insulin
• Diabetes duration \>6 months
• HbA1c 7.0-10.0%

You may not qualify if:

• Acute illness or infection
• Recent (within 1 month) surgery, trauma, cardiovascular event
• Recent (within 3 months) variation of statin therapy/dose
• Therapy with HDL-modifying drugs, such as fibrates, omega-3 fatty acids, and niacin
• Alcoholism
• Very high baseline HDL levels (\>90 mg/dL)
• History of hypotension, episodes of volume depletion / dehydration.
• Chronic renal failure (eGFR\<60 ml/min/1.73 mq)
• Chronic liver disease (SGOT or GPT \>2-fold ULN, or cirrhosis)
• Elevated hematocrit (\>50% for men or \>45% for women)
• Heart failure, NYHA classes III-IV
• Hypersensitivity to Dapagliflozin or its excipients
• Treatment with pioglitazone or GLP-1 receptor agonists
• Women with childbearing potential

Sponsors & Collaborators

• University of Padova: lead
• Azienda Ospedaliera di Padova: collaborator

Study Sites (1)

Division of Metabolic Diseases, University Hospital of Padova

Padua, 35128, Italy

Location

Related Publications (2)

• Bonora BM, Vigili de Kreutzenberg S, Avogaro A, Fadini GP. Effects of the SGLT2 inhibitor dapagliflozin on cardiac function evaluated by impedance cardiography in patients with type 2 diabetes. Secondary analysis of a randomized placebo-controlled trial. Cardiovasc Diabetol. 2019 Aug 14;18(1):106. doi: 10.1186/s12933-019-0910-5.

  PMID: 31412874 DERIVED

• Fadini GP, Bonora BM, Zatti G, Vitturi N, Iori E, Marescotti MC, Albiero M, Avogaro A. Effects of the SGLT2 inhibitor dapagliflozin on HDL cholesterol, particle size, and cholesterol efflux capacity in patients with type 2 diabetes: a randomized placebo-controlled trial. Cardiovasc Diabetol. 2017 Apr 4;16(1):42. doi: 10.1186/s12933-017-0529-3.

  PMID: 28376855 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2014
• First Posted: December 30, 2014
• Study Start: March 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: August 2, 2019

Record last verified: 2019-07

Locations

IT (1)