Physical ActivityPhase 2NCT02371187
Does Dapagliflozin Augment The Favorable Adaptation To Endurance Exercise Training?
A Phase 2 study testing Dapagliflozin in people with Physical Activity, run by Christopher Bell at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Physical Activity
- What is being tested?
- Dapagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to Jan 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
- 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.
Show all 22Show fewer
- 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.
- 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 enrollment; 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 enrollment; less than two months post coronary artery re-vascularization; 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 enrollment: Systolic blood pressure ≥165 mmHg and/or diastolic blood pressure ≥100 mmHg.
- Blood pressure at randomization: Systolic blood pressure ≥165 mmHg and/or diastolic blood pressure ≥100 mmHg
- Patients who, in the judgment of the medical monitor, may be at risk for dehydration.
Trial locations and contacts
1 site in 1 country.
United States1 site
Colorado State University, Dept. of Health and Exercise Science
Fort Collins, Colorado, 80523-1582
About this study
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.
Read the detailed description
This is a randomized, placebo-controlled, double blind, repeated measures study. 30 sedentary adults will be recruited for participation and randomly assigned to one of two 12-week treatments: 1) supervised endurance exercise training 4 days per week plus daily oral administration of Dapagliflozin; 2) supervised endurance exercise training 4 days per week plus daily oral administration of placebo. Prior to and following completion of the treatment the following dependent variables will be quantified: a) maximal aerobic capacity; b) substrate utilization during standardized low-moderate intensity exercise; c) skeletal muscle aerobic enzyme activity; d) body composition; and, e) oral glucose tolerance, fasting glucose and insulin resistance.
The dose of Dapagliflozin will begin as 5 mg/day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to 10 mg/day for the remainder of the study.
- Conditions
- Physical Activity
- Being tested
- Dapagliflozin, Placebo
- Medical subject headings
- Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
Also called Farxiga
Dapagliflozin tablets, 5 mg, one per day for the first 14 days, increase to two per day for 70 days.
PlaceboDrug
Matching placebo for Dapagliflozin 5 mg, one per day for the first 14 days, increase to two per day for 70 days.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline of Maximal Oxygen Uptake at Week 12
Indirect calorimetry
Measured: 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.
Measured: 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
Measured: 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.
Measured: Baseline, 12 weeks
Change From Baseline of Fat Free Mass at Week 12
Via dual energy X-ray absorptiometry
Measured: Baseline, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2015 (estimated)
- Study startJun 2015
- Primary completionJan 2018
- Study completionJan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Physical ActivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christopher Bell
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor-investigator, Christopher Bell, Colorado State University
- Investigators
- Christopher Bell, PhD, Principal investigator, Colorado State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02371187
- Sponsor's protocol ID
- 14-5529H
- Status last verified
- Mar 2019
- First submitted
- 13 Feb 2015
- Last updated
- 10 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 30597042
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Dapagliflozin Augment The Favorable Adaptation To Endurance Exercise Training?
- ClinicalTrials.gov ID
- NCT02371187
- Acronym / sponsor ID
- 14-5529H
- Conditions
- Physical Activity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Christopher BellUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Jun 2015 (actual)
- Primary completion
- Jan 2018 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 25 Feb 2015 (estimated)
- Results
- Posted 10 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a randomized, placebo-controlled, double blind, repeated measures study. 30 sedentary adults will be recruited for participation and randomly assigned to one of two 12-week treatments: 1) supervised endurance exercise training 4 days per week plus daily oral administration of Dapagliflozin; 2) supervised endurance exercise training 4 days per week plus daily oral administration of placebo. Prior to and following completion of the treatment the following dependent variables will be quantified: a) maximal aerobic capacity; b) substrate utilization during standardized low-moderate intensity exercise; c) skeletal muscle aerobic enzyme activity; d) body composition; and, e) oral glucose tolerance, fasting glucose and insulin resistance.
The dose of Dapagliflozin will begin as 5 mg/day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to 10 mg/day for the remainder of the study.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin | Experimental | Drug: DapagliflozinThe 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. |
| Placebo | Placebo comparator | Drug: PlaceboMatching 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (22 listed)
- Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DapagliflozinAlso: FarxigaDapagliflozin tablets, 5 mg, one per day for the first 14 days, increase to two per day for 70 days. | Drug | Dapagliflozin |
| PlaceboMatching placebo for Dapagliflozin 5 mg, one per day for the first 14 days, increase to two per day for 70 days. | Drug | Placebo |
Primary outcome
Change From Baseline of Maximal Oxygen Uptake at Week 12
Time frame: Baseline,12 weeks
Indirect calorimetry
Change From Baseline of Respiratory Exchange Ratio at Week 12
Time frame: Baseline, 12 weeks
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.
Change From Baseline of Maximal Aerobic Enzyme Activities in Skeletal Muscle at Week 12
Time frame: Baseline, 12 weeks
Maximal citrate synthase activity in skeletal muscle sample
Change From Baseline of Insulin Sensitivity at Week 12
Time frame: Baseline, 12 weeks
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.
Change From Baseline of Fat Free Mass at Week 12
Time frame: Baseline, 12 weeks
Via dual energy X-ray absorptiometry
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30597042Newman 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.
- Individual participant dataSharing planned: No
Related trials for Physical Activity
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruiting
Feasibility of a Robot-Guided Active Play Intervention for Children With Cerebral Palsy
Cerebral Palsy
Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
Recruiting
Effect of a Brief Daily Digital Meditation on Well-Being in US Young Adults (BEGIN II)
Mental Health and General Well-being
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Bell, PhD principal investigator
Colorado State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dapagliflozin in people with Physical Activity, run by Christopher Bell at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline of Maximal Oxygen Uptake at Week 12 (time frame: Baseline,12 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02371187, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2019.