Dapagliflozin Effects on Epicardial Fat

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT02235298
• Collaborator: AstraZeneca (Industry)
• Enrollment: 100
• Location: 1
• Arms: 2
• Actual Duration (Months): 60.3
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

The purpose of this research study is to learn about the effect of Dapagliflozin (Farxiga) on the fat of the heart.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Dapagliflozin; Drug: Metformin; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effects of Dapagliflozin on Epicardial Fat in Subjects With Type 2 Diabetes
• Actual Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Sep 10, 2020
• Actual Study Completion Date: Sep 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dapagliflozin and Metformin Group Participants in this group will receive Dapagliflozin in addition to Metformin for 6 months.	Drug: Dapagliflozin; 5 mg taken orally once daily. After 2 weeks, if there are no safety issues as per treating physician discretion, the dose can be titrated up to 10 mg orally taken once daily.; Other Names: Farxiga ; Drug: Metformin; 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL
Active Comparator: Metformin and Placebo Group Participants in this group will receive Metformin and Placebo for 6 months.	Drug: Metformin; 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL; Drug: Placebo; Placebo pill taken once daily to mimic Dapagliflozin

Outcome Measures

Primary Outcome Measures

1. Epicardial Fat Thickness [At Baseline, 12 weeks, 24 weeks]

   Epicardial fat thickness will be measured in millimeters by treating physician using echocardiography at Baseline, 12 weeks, 24 weeks

Secondary Outcome Measures

1. Left Ventricular Mass (LVM) [At Baseline, Week 12 and Week 24]

   LVM will be measured in g/m^2 by treating physician using echocardiography at baseline, Week 12 and Week 24

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes, as defined by ADA criteria

• HbA1c < 8% measured at least 1 week prior to the study

• BMI ≥27 kg/m2

• Pre-treatment with Metformin as monotherapy

• Age > 18 and < 65 years old

• Normal and stable hemodynamic status

Exclusion Criteria:

• Known contra-indications to Farxiga, in accordance with risks and safety information included in the latest updated Prescribing Information

• Type 1 diabetes, as defined by American Diabetes Association (ADA) criteria

• Insulin dependent or treated type 2 diabetes

• Current use of other SGLT2 inhibitors, Glucagon Like Peptide -1 (GLP- 1) analogs or Dipeptidyl Peptidase 4 (DPP4) inhibitors

• Glomerular Filtration Rate (GFR) < 60 mL/min/1.73 m2

• Signs or symptoms of hypovolemia

• Patients with poor glycemic control (HbA1c ≥ 8%) will be excluded to maximize long-term patient retention without need

• History of diabetes ketoacidosis

• Patients with active bladder cancer or with a prior history of bladder cancer

• Acute or chronic infective, including genital mycotic infections

• Clinical signs or symptoms of New York Heart Association (NYHA) class III-IV heart failure

• Clinical or laboratory evidences of chronic active liver diseases

• Acute or chronic infective diseases

• Cancer or chemotherapy

• Current use of systemic corticosteroids or in the 3 months prior this study

• Known or suspected allergy to Dapagliflozin, excipients, or related products

• Pregnant, breast-feeding or the intention of becoming pregnant

• Females of childbearing potential who are not using adequate contraceptive methods

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami
• AstraZeneca

Investigators

• Principal Investigator: Gianluca Iacobellis, MD, PhD, University of Miami

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 24, 2014

More Information

Publications

None provided.

• Responsible Party: Gianluca Iacobellis, Professor of Clinical Medicine, University of Miami
• ClinicalTrials.gov Identifier: NCT02235298
• Other Study ID Numbers: 20140671
• First Posted: Sep 9, 2014
• Last Update Posted: Feb 16, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Gianluca Iacobellis, Professor of Clinical Medicine, University of Miami: epicardial fat; diabetes; dapagliflozin
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Metformin; Dapagliflozin

Study Results

Participant Flow

Arm/Group Title	Dapagliflozin and Metformin Group	Metformin and Placebo Group
Arm/Group Description	Participants in this group will receive Dapagliflozin in addition to Metformin for 6 months. Dapagliflozin: 5 mg taken orally once daily. After 2 weeks, if there are no safety issues as per treating physician discretion, the dose can be titrated up to 10 mg orally taken once daily. Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL	Participants in this group will receive Metformin and Placebo for 6 months. Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL Placebo: Placebo pill taken once daily to mimic Dapagliflozin
Period Title: Overall Study
STARTED	50	50
COMPLETED	42	42
NOT COMPLETED	8	8

Baseline Characteristics

Arm/Group Title	Dapagliflozin and Metformin Group	Metformin and Placebo Group	Total
Arm/Group Description	Participants in this group will receive Dapagliflozin in addition to Metformin for 6 months. Dapagliflozin: 5 mg taken orally once daily. After 2 weeks, if there are no safety issues as per treating physician discretion, the dose can be titrated up to 10 mg orally taken once daily. Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL	Participants in this group will receive Metformin and Placebo for 6 months. Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL Placebo: Placebo pill taken once daily to mimic Dapagliflozin	Total of all reporting groups
Overall Participants	50	50	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52 (9)	51 (11)	51.5 (10)
Sex: Female, Male (Count of Participants)
Female	29 58%	30 60%	59 59%
Male	21 42%	20 40%	41 41%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	25 50%	22 44%	47 47%
Not Hispanic or Latino	25 50%	28 56%	53 53%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Epicardial Fat Thickness
Description	Epicardial fat thickness will be measured in millimeters by treating physician using echocardiography at Baseline, 12 weeks, 24 weeks
Time Frame	At Baseline, 12 weeks, 24 weeks

Outcome Measure Data

Analysis Population Description

Data is reported only for the participants that completed the study intervention.

Arm/Group Title	Dapagliflozin and Metformin Group	Metformin and Placebo Group
Arm/Group Description	Participants in this group will receive Dapagliflozin in addition to Metformin for 6 months. Dapagliflozin: 5 mg taken orally once daily. After 2 weeks, if there are no safety issues as per treating physician discretion, the dose can be titrated up to 10 mg orally taken once daily. Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL	Participants in this group will receive Metformin and Placebo for 6 months. Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL Placebo: Placebo pill taken once daily to mimic Dapagliflozin
Measure Participants	42	42
Baseline	8.6 (2.2)	8.0 (2.5)
12 Weeks	7.2 (2.3)	7.4 (2.5)
24 Weeks	6.7 (2.1)	7.5 (2.4)

2. Secondary Outcome

Title	Left Ventricular Mass (LVM)
Description	LVM will be measured in g/m^2 by treating physician using echocardiography at baseline, Week 12 and Week 24
Time Frame	At Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

Due to time and technical limitations, LVM data were not collected for all participants that completed the study intervention.

Arm/Group Title	Dapagliflozin and Metformin Group	Metformin and Placebo Group
Arm/Group Description	Participants in this group will receive Dapagliflozin in addition to Metformin for 6 months. Dapagliflozin: 5 mg taken orally once daily. After 2 weeks, if there are no safety issues as per treating physician discretion, the dose can be titrated up to 10 mg orally taken once daily. Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL	Participants in this group will receive Metformin and Placebo for 6 months. Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL Placebo: Placebo pill taken once daily to mimic Dapagliflozin
Measure Participants	33	24
Baseline	129 (13)	130 (19)
Week 12	127 (18)	128 (20)
Week 24	122 (19)	122 (20)

Adverse Events

Time Frame	24 Weeks
Arm/Group Title	Dapagliflozin and Metformin Group		Metformin and Placebo Group
Arm/Group Description	Participants in this group will receive Dapagliflozin in addition to Metformin for 6 months. Dapagliflozin: 5 mg taken orally once daily. After 2 weeks, if there are no safety issues as per treating physician discretion, the dose can be titrated up to 10 mg orally taken once daily. Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL		Participants in this group will receive Metformin and Placebo for 6 months. Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL Placebo: Placebo pill taken once daily to mimic Dapagliflozin
All Cause Mortality
	Dapagliflozin and Metformin Group		Metformin and Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)
Serious Adverse Events
	Dapagliflozin and Metformin Group		Metformin and Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Dapagliflozin and Metformin Group		Metformin and Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/50 (16%)		2/50 (4%)
Gastrointestinal disorders
Diarrhea	0/50 (0%)	0	2/50 (4%)	2
Abdominal Distention	0/50 (0%)	0	2/50 (4%)	2
Renal and urinary disorders
Urinary Tract Infection	1/50 (2%)	1	0/50 (0%)	0
Balanitis	1/50 (2%)	1	0/50 (0%)	0
Frequency of Urination	6/50 (12%)	6	0/50 (0%)	0
Dysuria	6/50 (12%)	6	0/50 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.