Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight Loss?
Condition: Weight Loss
MeSH terms: Body Weight; Weight Loss
Intervention: Dapagliflozin Tablet; Placebo Tablet
Intervention description: Daily oral administration of dapagliflozin with dietary counseling to promote weight loss. Dapagliflozin 5 mg tablet 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.; Daily administration of placebo tablet with dietary counseling to promote weight loss. Matching placebo for dapagliflozin 5 mg tablet 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.
Intervention MeSH terms: Dapagliflozin
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Dapagliflozin is a medicine to treat diabetes. Its mechanism of action is via sodium-glucose
      co-transporter 2 (SGLT2) inhibition. In adults with diabetes, use of sodium-glucose
      co-transporter 2 inhibitors 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. We wish to compare the
      health benefits of dietary counseling for weight loss with and without concomitant use of an
      SGLT2 inhibitor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provision of informed consent prior to any study specific procedures.

          -  Aged 18-65 years.

          -  No known Type 2 Diabetes

          -  Body mass index greater than or equal to 27.5 kg/m^2

          -  Limited exercise participation (maximum of 3/week regularly scheduled activity
             sessions of < 30 minutes during the previous month).

          -  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)

          -  Agree to abide by the study schedule and dietary restrictions and to return for the
             required assessments

          -  Women of childbearing potential must have negative pregnancy test and be using
             acceptable contraception

        Exclusion Criteria:

          -  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.

          -  Use of prescription drugs (see exceptions listed below) or herbal preparations in the
             2 weeks before study commencement. Prior use of medication or herbal preparations in
             the 4 weeks before study commencement that are intended for weight-loss and/or
             sold/marketed as weight-loss products or may alter metabolism. Permitted Prescription
             Drugs: Birth Control, Less than a 7 day short course of antibiotics. Note: Rifampicin
             is not permitted. Other medicines, such as those for gastroesophageal reflux disease,
             depression, and Over The Counter analgesics and allergy medications,may be allowed,
             but will be approved on a case-by-case basis.

          -  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.

          -  Habitual and/or recent use (within 2 years) of tobacco.

          -  Being considered unsuitable for participation in this trial for any reason, as judged
             by the investigator or medical monitor.

          -  History of serious hypersensitivity reaction to Dapagliflozin.

          -  Severe renal impairment, end-stage renal disease, or dialysis.

          -  Pregnant or breastfeeding individual.

          -  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.

          -  Total bilirubin >2.0 mg/dL (34.2 umol/L).

          -  Positive serologic evidence of current infectious liver disease including Hepatitis B
             viral antibody immunoglobulin M, Hepatitis B surface antigen and Hepatitis C virus
             antibody.

          -  Estimated Glomerular Filtration Rate <60 mL/min/1.73 m^2 (calculated by
             Cockcroft-Gault formula).

          -  History of bladder cancer.

          -  Recent cardiovascular events in a patient, including any of the following: acute
             coronary syndrome within 2 months prior to enrolment; hospitalization for unstable
             angina or acute myocardial infarction within 2 months prior to enrolment; acute stroke
             or trans-ischemic attack within two months prior to enrolment; 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.

          -  Blood pressure at enrolment: Systolic blood pressure ≥160 mmHg and/or diastolic blood
             pressure ≥100 mmHg.

          -  Blood pressure at randomization: Systolic blood pressure ≥165 mmHg and/or diastolic
             blood pressure ≥100 mmHg

          -  Individuals who, in the judgment of the medical monitor, may be at risk for
             dehydration.

          -  Individuals with a history of fragility fracture, or bone mineral density values
             reflective of risk for fracture (DEXA Z-score <or= to -2 in pre-menopausal women, and
             men <50, and T-score <or= to -1) will not be permitted to participate.