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

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ClinicalTrials.gov Identifier: NCT02520518
Recruitment Status : Terminated (Designed a new modified/simplified protocol see NCT 03180489)
First Posted : August 13, 2015
Results First Posted : December 11, 2018
Last Update Posted : January 3, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Christopher Bell, Colorado State University

Tracking Information
First Submitted Date  ICMJE July 27, 2015
First Posted Date  ICMJE August 13, 2015
Results First Submitted Date  ICMJE August 14, 2018
Results First Posted Date  ICMJE December 11, 2018
Last Update Posted Date January 3, 2019
Study Start Date  ICMJE August 2015
Actual Primary Completion Date May 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 16, 2018)
  • Change From Baseline in Insulin Sensitivity at Week 12 [ Time Frame: Baseline,12 weeks ]
    Via oral glucose tolerance test.
  • Change From Baseline in Blood Pressure at Week 12 [ Time Frame: Baseline, 12 weeks ]
  • Change From Baseline in Perception of Satiety at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Perceptions of satiety will be determined using a visual analog scale called a Hunger Rating Scales. The minimum value is 1 (not at all full) and the maximum value is 100 (extremely full). One value between 1 and 100 is reported by the participant dependent on their perception. No sub scores are used. The perceived values are reported as the group average at baseline and 12 weeks. There is not a better or worse outcome, but rather a measure of perceived satiety. If Dapagliflozin were effective at increasing fullness, respondents would exhibit 12-week scores for the question in comparison to their baseline scores.
  • Change From Baseline in Perception of Hunger at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Perceptions of Hunger will be determined using a visual analog scale called a Hunger Rating Scales. The minimum value is 1 (not at all hungry) and the maximum value is 100 (very hungry). One value between 1 and 100 is reported by the participant dependent on their perception. No sub scores are used. The perceived values are reported as the group average at baseline and 12 weeks. There is not a better or worse outcome, but rather a measure of perceived hunger. If Dapagliflozin were effective at decreasing hunger, respondents would exhibit 12-week scores for the question in comparison to their baseline scores.
  • Change From Baseline in Marker of Inflammation (High Sensitive C-reactive Protein) at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Marker of Inflammation (Tumor Necrosis Factor Alpha) at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Marker of Inflammation (Interleukin 6) at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Hunger Hormone Ghrelin at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Hunger Hormone Peptide Tyrosine Tyrosine at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Maker of Oxidative Stress (Oxidized Low Density Lipoprotein) at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Maker of Oxidative Stress (Low Density Thiobarbituric Acid Reactive Substances) at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Satiety Hormone Leptin at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Satiety Hormone Insulin at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
Original Primary Outcome Measures  ICMJE
 (submitted: August 7, 2015)
  • Change From Baseline in Insulin Sensitivity at Week 12 [ Time Frame: Baseline,12 weeks ]
    Via oral glucose tolerance test.
  • Change From Baseline in Blood Pressure at Week 12 [ Time Frame: Baseline, 12 weeks ]
  • Change From Baseline in Perception of Satiety at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Perceptions of satiety will be determined using a visual analog scale.
  • Change From Baseline in Perception of Hunger at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Perceptions of hunger will be determined using a visual analog scale.
  • Change From Baseline in Marker of Inflammation (High Sensitive C-reactive Protein) at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Marker of Inflammation (Tumor Necrosis Factor Alpha) at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Marker of Inflammation (Interleukin 6) at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Hunger Hormone Ghrelin at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change from baseline in hunger hormone peptide YY at week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Maker of Oxidative Stress (Oxidized Low Density Lipoprotein) at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Maker of Oxidative Stress (Low Density Thiobarbituric Acid Reactive Substances) at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Satiety Hormone Leptin at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
  • Change From Baseline in Satiety Hormone Insulin at Week 12 [ Time Frame: Baseline, 12 weeks ]
    Will be analyzed using a commercially available biochemical assay.
Change History Complete list of historical versions of study NCT02520518 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Does Dapagliflozin Promote Favorable Health Benefits That Are Independent Of Weight Loss?
Official Title  ICMJE Does Dapagliflozin Promote Favorable Health Benefits That Are Independent Of Weight Loss?
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Weight Loss
Intervention  ICMJE
  • Drug: Dapagliflozin
    Other Name: Farxiga
  • Drug: Placebo
  • Behavioral: Weight maintenance
  • Behavioral: Ad libitum dietary intake
  • Behavioral: Dietary restriction
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: Dapagliflozin
    • Behavioral: Ad libitum dietary intake
  • Experimental: 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.
    Interventions:
    • Drug: Dapagliflozin
    • Behavioral: Weight maintenance
  • Placebo Comparator: 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.
    Interventions:
    • Drug: Placebo
    • Behavioral: Ad libitum dietary intake
  • Placebo Comparator: 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.
    Interventions:
    • Drug: Placebo
    • Behavioral: Dietary restriction
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 16, 2018)
9
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2015)
92
Actual Study Completion Date  ICMJE May 2017
Actual Primary Completion Date May 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02520518
Other Study ID Numbers  ICMJE 14-5531H
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Christopher Bell, Colorado State University
Study Sponsor  ICMJE Christopher Bell
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE Not Provided
PRS Account Colorado State University
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP