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

NCT02520518 | Terminated Phase 2 Results

• 1 other identifier: 14-5531H
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Weight Loss

Outcome Measures

Primary Outcomes (13)

• Change From Baseline in Insulin Sensitivity at Week 12

  Via oral glucose tolerance test.

  Baseline,12 weeks

• Change From Baseline in Blood Pressure at Week 12

  Baseline, 12 weeks

• Change From Baseline in Perception of Satiety at Week 12

  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.

  Baseline, 12 weeks

• Change From Baseline in Perception of Hunger at Week 12

  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.

  Baseline, 12 weeks

• Change From Baseline in Marker of Inflammation (High Sensitive C-reactive Protein) at Week 12

  Will be analyzed using a commercially available biochemical assay.

  Baseline, 12 weeks

• Change From Baseline in Marker of Inflammation (Tumor Necrosis Factor Alpha) at Week 12

  Will be analyzed using a commercially available biochemical assay.

  Baseline, 12 weeks

• Change From Baseline in Marker of Inflammation (Interleukin 6) at Week 12

  Will be analyzed using a commercially available biochemical assay.

  Baseline, 12 weeks

• Change From Baseline in Hunger Hormone Ghrelin at Week 12

  Will be analyzed using a commercially available biochemical assay.

  Baseline, 12 weeks

• Change From Baseline in Hunger Hormone Peptide Tyrosine Tyrosine at Week 12

  Will be analyzed using a commercially available biochemical assay.

  Baseline, 12 weeks

• Change From Baseline in Maker of Oxidative Stress (Oxidized Low Density Lipoprotein) at Week 12

  Will be analyzed using a commercially available biochemical assay.

  Baseline, 12 weeks

• Change From Baseline in Maker of Oxidative Stress (Low Density Thiobarbituric Acid Reactive Substances) at Week 12

  Will be analyzed using a commercially available biochemical assay.

  Baseline, 12 weeks

• Change From Baseline in Satiety Hormone Leptin at Week 12

  Will be analyzed using a commercially available biochemical assay.

  Baseline, 12 weeks

• Change From Baseline in Satiety Hormone Insulin at Week 12

  Will be analyzed using a commercially available biochemical assay.

  Baseline, 12 weeks

Study Arms (4)

Dapagliflozin: ad libitum dietary intake

EXPERIMENTAL

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.

Drug: Dapagliflozin; Behavioral: Ad libitum dietary intake

Dapagliflozin: weight maintenance

EXPERIMENTAL

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.

Drug: Dapagliflozin; Behavioral: Weight maintenance

Placebo: ad libitum dietary intake

PLACEBO COMPARATOR

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.

Drug: Placebo; Behavioral: Ad libitum dietary intake

Placebo: dietary restriction

PLACEBO COMPARATOR

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.

Drug: Placebo; Behavioral: Dietary restriction

Interventions

Dapagliflozin DRUG

Also known as: Farxiga

Dapagliflozin: ad libitum dietary intake; Dapagliflozin: weight maintenance

Placebo DRUG

Placebo: ad libitum dietary intake; Placebo: dietary restriction

Weight maintenance BEHAVIORAL

Dapagliflozin: weight maintenance

Ad libitum dietary intake BEHAVIORAL

Dapagliflozin: ad libitum dietary intake; Placebo: ad libitum dietary intake

Dietary restriction BEHAVIORAL

Placebo: dietary restriction

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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 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.
• 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 patients
• 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

Sponsors & Collaborators

• Christopher Bell: lead
• AstraZeneca: collaborator

Study Sites (1)

Colorado State University, Dept. of Health and Exercise Science

Fort Collins, Colorado, 80523-1582, United States

Location

MeSH Terms

Conditions

Weight Loss

Interventions

dapagliflozin; Body Weight Maintenance; Diet Therapy

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Body Weight; Body Size; Growth; Growth and Development; Physiological Phenomena; Nutrition Therapy; Therapeutics

Results Point of Contact

• Title: Manager of Research Operations
• Organization: COLORADO STATE UNIVERSITY

Laurie.Biela@colostate.edu

970-491-2242

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 27, 2015
• First Posted: August 13, 2015
• Study Start: August 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: January 3, 2019
• Results First Posted: December 11, 2018

Record last verified: 2018-12

Locations

US (1)