Does Dapagliflozin Promote Favorable Health Benefits That Are Independent Of Weight Loss?

NCT ID: NCT02520518

Last Updated: 2019-01-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2017-05-31

Brief Summary

Th mechanism of action of dapagliflozin is via sodium-glucose co-transporter 2 (SGLT2) inhibition. Sodium-glucose co-transporter 2 inhibition is associated with moderate weight (fat) loss, in addition to other health benefits, including decreased blood pressure, decreased inflammation, and decreased oxidative stress. It is unclear as to whether these health benefits are due to SGLT2 inhibition per se, or as a secondary effect of weight loss.

Detailed Description

This is a randomized, prospective, placebo-controlled, double-blind, repeated measures study. 92 overweight/obese adults (body mas index > 27.5 kg/m^2) will be recruited for participation and randomly assigned to one of four 12 week treatments: 1) daily oral administration of dapagliflozin with ad-libitum dietary intake; 2) daily oral administration of dapagliflozin with supplemented dietary intake to achieve weight maintenance; 3) daily oral administration of a placebo plus dietary restriction such that weight loss is matched to participants in treatment 1; or, 4) daily oral administration of a placebo with ad-libitum dietary intake.

Conditions

Weight Loss

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Dapagliflozin: ad libitum dietary intake

Daily oral administration of dapagliflozin with ad libitum dietary intake. The dose of dapagliflozin will begin as one 5 mg tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two 5 mg tablets per day for the remainder of the study.

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Ad libitum dietary intake

Intervention Type: BEHAVIORAL

Dapagliflozin: weight maintenance

Daily oral administration of dapagliflozin with supplemented dietary intake to achieve weight maintenance. The dose of dapagliflozin will begin as one 5 mg tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two 5 mg tablets per day for the remainder of the study.

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Weight maintenance

Intervention Type: BEHAVIORAL

Placebo: ad libitum dietary intake

Daily oral administration of a placebo with ad-libitum dietary intake. Matching placebo for dapagliflozin 5 mg will begin as one tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two tablets for the remainder of the study.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Ad libitum dietary intake

Intervention Type: BEHAVIORAL

Placebo: dietary restriction

Daily oral administration of a placebo plus dietary restriction such that weight loss is matched to participants in Arm 1. Matching placebo for dapagliflozin 5 mg will begin as one tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two tablets for the remainder of the study.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Dietary restriction

Intervention Type: BEHAVIORAL

Interventions

Dapagliflozin

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Weight maintenance

Intervention Type: BEHAVIORAL

Ad libitum dietary intake

Intervention Type: BEHAVIORAL

Dietary restriction

Intervention Type: BEHAVIORAL

Other Intervention Names

Farxiga

Eligibility Criteria

Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures.

2. Aged 18-65 years.

3. No known Type 2 Diabetes

4. Body mass index greater than or equal to 27.5 kg/m^2

5. Sedentary (maximum of 2/week regularly scheduled activity sessions of < 20 minutes during the previous 2 years)

6. Completion of a screening visit consisting of medical history, physical examination, and 12-lead electrocardiogram and blood pressure assessment at rest and during incremental exercise to volitional exhaustion (Note: Subjects with abnormal screening values may be eligible if the results are not clinically significant, as judged by the investigator or medical monitor)

7. Agree to abide by the study schedule and dietary restrictions and to return for the required assessments

8. Women of childbearing potential must have negative pregnancy test and be using acceptable contraception

Exclusion Criteria

1. Evidence of clinically significant cardiovascular, respiratory, renal, hepatic, pulmonary, gastrointestinal, haematological, neurological, psychiatric, or other disease that may interfere with the objectives of the study or the safety of the subject, as judged by the investigator in agreement with the sponsor or medical monitor, have been hospitalized in the past 2 years as a result of these conditions, or are receiving pharmacological treatment for these conditions

2. Use of prescription drugs (see exceptions listed below) or herbal preparations in the 4 weeks before study commencement.

Permitted Prescription Drugs

• Birth Control
• Less than 7 days, short course antibiotics. Note: Rifampin is not permitted.
• Other medicines, for Gastroesophageal Reflux Disease (GERD), depression, seasonal allergies and over-the-counter analgesics, maybe allowed, but will be approved on a case-by-case basis.

3. Is currently enrolled in another clinical study for another investigational drug or has taken any other investigational drug within 30 days before the screening visit.

4. Habitual and/or recent use (within 2 years) of tobacco

5. Being considered unsuitable for participation in this trial for any reason, as judged by the investigator or medical monitor.

6. History of serious hypersensitivity reaction to dapagliflozin

7. Severe renal impairment, end-stage renal disease, or dialysis

8. Pregnant or breastfeeding patients

9. Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal and/or alanine aminotransferase (ALT) >3x upper limit of normal

10. Total bilirubin >2.0 mg/dL (34.2 umol/L)

11. Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody Immunoglobulin M, Hepatitis B surface antigen and Hepatitis C virus antibody

12. Estimated Glomerular Filtration Rate <60 mL/min/1.73 m^2 (calculated by Cockcroft-Gault formula).

13. History of bladder cancer

14. Recent cardiovascular events in a patient, including any of the following: acute coronary syndrome within 2 months prior to enrollment; hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrollment; acute stroke or trans-ischemic attack within two months prior to enrollment; less than two months post coronary artery revascularization; congestive heart failure defined as New York Heart Association class IV,unstable or acute congestive heart failure. Note: eligible patients with congestive heart failure, especially those who are on diuretic therapy, should have careful monitoring of their volume status throughout the study

15. Blood pressure at enrolment: Systolic blood pressure ≥165 mmHg and/or diastolic blood pressure ≥100 mmHg

16. Blood pressure at randomization: Systolic blood pressure ≥165 mmHg and/or diastolic blood pressure ≥100 mmHg

17. Patients who, in the judgment of the medical monitor, may be at risk for dehydration

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Christopher Bell

OTHER

Sponsor Role: lead

Responsible Party

Christopher Bell

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Colorado State University, Dept. of Health and Exercise Science

Fort Collins, Colorado, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

14-5531H

Identifier Type: -

Identifier Source: org_study_id