Does Dapagliflozin Augment The Favorable Adaptation To Endurance Exercise Training?

NCT02371187 | Completed Phase 2 Results

• 1 other identifier: 14-5529H
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Exercise is frequently prescribed as a favorable lifestyle intervention to prevent/reverse type 2 diabetes. It is also prescribed in addition to concurrent pharmacological treatment, such as metformin. Recent data (animal and human) suggest that metformin may attenuate the favorable benefits of exercise training. In light of the physiological mechanism of Dapagliflozin (sodium-glucose co-transporter 2 (SGLT2) inhibition), one might speculate that rather than inhibit, it will augment the favorable adaptations to exercise training.

Conditions

Physical Activity

Outcome Measures

Primary Outcomes (5)

• Change From Baseline of Maximal Oxygen Uptake at Week 12

  Indirect calorimetry

  Baseline,12 weeks

• Change From Baseline of Respiratory Exchange Ratio at Week 12

  The respiratory exchange ratio (RER) is the ratio between the amount of carbon dioxide (CO2) produced in metabolism and oxygen (O2) used during standardized exercise.

  Baseline, 12 weeks

• Change From Baseline of Maximal Aerobic Enzyme Activities in Skeletal Muscle at Week 12

  Maximal citrate synthase activity in skeletal muscle sample

  Baseline, 12 weeks

• Change From Baseline of Insulin Sensitivity at Week 12

  Insulin Sensitivity was estimated by measuring circulating glucose and insulin concentrations after a 12-hour fast and after ingestion of 75 g of glucose. Glucose was measured 5, 10, 15, 20, 30, 45, 60, 75, 90, 105 and 120 minutes after glucose ingestion. Insulin was measured 15, 30, 45, 60, 90 and 120 minutes after glucose ingestion. Insulin sensitivity was estimated using the Matsuda Index, represented by the formula: Matsuda index = 10,000/SQRT \[fasting glucose\*fasting insulin\* (mean glucose from time 5, 10, 15, 20, 30, 45, 60, 75, 90, 105 and 120 minutes) \* (mean insulin from time 15, 30, 45, 60, 90 and 120 minutes)\], with higher numbers indicating better insulin sensitivity.

  Baseline, 12 weeks

• Change From Baseline of Fat Free Mass at Week 12

  Via dual energy X-ray absorptiometry

  Baseline, 12 weeks

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Dapagliflozin DRUG

Dapagliflozin tablets, 5 mg, one per day for the first 14 days, increase to two per day for 70 days.

Also known as: Farxiga

Dapagliflozin

Placebo DRUG

Matching placebo for Dapagliflozin 5 mg, one per day for the first 14 days, increase to two per day for 70 days.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of informed consent prior to any study specific procedures.
• No known Type 2 Diabetes.
• Body mass index 25-45 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 to return for the required assessments.
• Be willing and able to repeatedly perform exercise.
• 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, hematological, 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, 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 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

Related Publications (1)

• Newman AA, Grimm NC, Wilburn JR, Schoenberg HM, Trikha SRJ, Luckasen GJ, Biela LM, Melby CL, Bell C. Influence of Sodium Glucose Cotransporter 2 Inhibition on Physiological Adaptation to Endurance Exercise Training. J Clin Endocrinol Metab. 2019 Jun 1;104(6):1953-1966. doi: 10.1210/jc.2018-01741.

  PMID: 30597042 DERIVED

MeSH Terms

Conditions

Motor Activity

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Behavior

Results Point of Contact

• Title: Manager of Research Operations
• Organization: Colorado State University

Laurie.Biela@colostate.edu

9704912242

Study Officials

• Christopher Bell, PhD

  Colorado State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: February 13, 2015
• First Posted: February 25, 2015
• Study Start: June 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: April 10, 2019
• Results First Posted: April 10, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)