Hepatic Glucose MetabolismPhase 4NCT03193684
Empagliflozin and Hepatic Glucose Metabolism
A Phase 4 study testing Empagliflozin 25 MG in people with Hepatic Glucose Metabolism, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
the aim of this study is to examine the role of autonomic nervous system in the increase in hepatic glucose production in response to glucosuria caused by inhibition of renal glucose uptake Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Glucose Metabolism
- What is being tested?
- Empagliflozin 25 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 20 May 2018to 30 Jan 2024
- Phase
- Phase 4
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- eGFR>60 ml/min healthy volunteers type 2 diabetes patients who otherwise healthy
Who cannot join
- eGFR <60 T2DM patients on insulin, GLP-1 RA or SGLT2 treatment Major organ disease type 1 diabetes
Trial locations and contacts
1 site in 1 country.
United States1 site
Diabetes Division, UTHSCSA
San Antonio, Texas, 78229
About this study
Official title: Effect of Empagliflozin on Hepatic Glucose Metabolism: Role of Autonomic Nervous System
the aim of this study is to examine the role of autonomic nervous system in the increase in hepatic glucose production in response to glucosuria caused by inhibition of renal glucose uptake
Read the detailed description
Purpose/Objectives: To investigate the effect of empagliflozin, an SGLT2 inhibitor on hepatic glucose production and the role of autonomic nervous system in mediating the increase in hepatic glucose production in response glucosuria Research Design/Plan: the role of autonomic nervous system in the increase in hepatic glucose production caused by empagliflozin will be examined with norepinephrine (NE) turnover in two protocols. The first protocol is cross sectional, in which 36 T2DM patients will receive hepatic glucose production (HGP) and NE turnover will be measured before and after empagliflozin or placebo administration. In protocol 2, diabetic and non-diabetic subjects will receive baseline HGP, NE turnover, hepatic glucose uptake (HGU) and liver fat measurement before at 2 days after the start and 12 weeks after empagliflozin or placebo treatment.
Methods: the following techniques will be employed (1) Measurement of hepatic glucose production with 3H-glucose infusion, with and without glucose clamp, (2) substrate oxidation with indirect calorimetry and plasma ketone/lactate/insulin/glucagon concentrations; (3) Measurement of HGU with Oral-IV double tracer infusion; (4) Measurement of whole body norepinephrine turnover with 3H-norepinephrine infusion; (5) Measurement of heart rate variability; (6) Measurement of liver fat content with 1H-MRS Clinical Relevance: The results of the present studies will help identify the mechanism responsible for the increase in HGP caused by empagliflozin and the increase in ketone production. The first action of the drug ameliorates its clinical efficacy while the second increases the risk of adverse events (ketoacidosis). Identifying the mechanisms underlying these actions will help developing therapeutic strategies which increase the drug clinical efficacy and mitigates its adverse events.
- Conditions
- Hepatic Glucose Metabolism
- Being tested
- Empagliflozin 25 MG, Control
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 25 MGDrug
subjects will receive daily dose of 25mg of empagliflozin for 3 months
ControlDrug
Also called Placebo
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | empagliflozin 25 mg per day Receives: Drug: Empagliflozin 25 MG |
| control | Placebo comparator | matching placebo 1 pill per day Receives: Drug: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of Empagliflozin on Autonomic Nervous System
autonomic activity will be measured with as NE turnover rate.
Total-body NE turnover rate was measured with 3H-NE infusion. A prime (3.8 µCi)-continuous (0.38 µCi/min) infusion of 3H-NE was started and continued for 60 minutes. Arterialized blood samples were collected before the start and between the 40-60 minute time period after the start of 3H-NE infusion. Total body NE turnover rate was calculated as the 3H-NE infusion rate (dpm/min) divided by the steady state plasma 3H-NE specific activity (dpm/pg) after 30 minutes
Measured: Baseline and 12 weeks
Secondary outcomes (1)
Hepatic Glucose Production
HGP will be measured with tracer dilution technique
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2017
- Study start20 May 2018
- Primary completion30 Jan 2023
- Study completion30 Jan 2024
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.
- Other trials for Hepatic Glucose MetabolismStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- subjects will receive in parallel a treatment with empagliflozin or placebo for 3 months hepatic glucose metabolism and norepinephrine turnover will be studied before and after treatment
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Muhammad Abdul-Ghani, MD, PhD, Principal investigator, Diabetes Division, UTHSCSA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03193684
- Sponsor's protocol ID
- HSC20170214H
- Other IDs
- 2R01DK097554-06
- Status last verified
- Aug 2024
- First submitted
- 17 Jun 2017
- Last updated
- 28 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Empagliflozin on Hepatic Glucose Metabolism: Role of Autonomic Nervous System
- ClinicalTrials.gov ID
- NCT03193684
- Acronym / sponsor ID
- HSC20170214H
- Conditions
- Hepatic Glucose Metabolism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 20 May 2018 (actual)
- Primary completion
- 30 Jan 2023 (actual)
- Study completion
- 30 Jan 2024 (actual)
- First posted
- 21 Jun 2017 (actual)
- Results
- Posted 28 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
the aim of this study is to examine the role of autonomic nervous system in the increase in hepatic glucose production in response to glucosuria caused by inhibition of renal glucose uptake
Detailed description
Purpose/Objectives: To investigate the effect of empagliflozin, an SGLT2 inhibitor on hepatic glucose production and the role of autonomic nervous system in mediating the increase in hepatic glucose production in response glucosuria Research Design/Plan: the role of autonomic nervous system in the increase in hepatic glucose production caused by empagliflozin will be examined with norepinephrine (NE) turnover in two protocols. The first protocol is cross sectional, in which 36 T2DM patients will receive hepatic glucose production (HGP) and NE turnover will be measured before and after empagliflozin or placebo administration. In protocol 2, diabetic and non-diabetic subjects will receive baseline HGP, NE turnover, hepatic glucose uptake (HGU) and liver fat measurement before at 2 days after the start and 12 weeks after empagliflozin or placebo treatment.
Methods: the following techniques will be employed (1) Measurement of hepatic glucose production with 3H-glucose infusion, with and without glucose clamp, (2) substrate oxidation with indirect calorimetry and plasma ketone/lactate/insulin/glucagon concentrations; (3) Measurement of HGU with Oral-IV double tracer infusion; (4) Measurement of whole body norepinephrine turnover with 3H-norepinephrine infusion; (5) Measurement of heart rate variability; (6) Measurement of liver fat content with 1H-MRS Clinical Relevance: The results of the present studies will help identify the mechanism responsible for the increase in HGP caused by empagliflozin and the increase in ketone production. The first action of the drug ameliorates its clinical efficacy while the second increases the risk of adverse events (ketoacidosis). Identifying the mechanisms underlying these actions will help developing therapeutic strategies which increase the drug clinical efficacy and mitigates its adverse events.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- subjects will receive in parallel a treatment with empagliflozin or placebo for 3 months hepatic glucose metabolism and norepinephrine turnover will be studied before and after treatment
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Empagliflozin 25 MGempagliflozin 25 mg per day |
| control | Placebo comparator | Drug: Controlmatching placebo 1 pill per day |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- eGFR>60 ml/min healthy volunteers type 2 diabetes patients who otherwise healthy
Key exclusion criteria (1 listed)
- eGFR <60 T2DM patients on insulin, GLP-1 RA or SGLT2 treatment Major organ disease type 1 diabetes
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 |
|---|---|---|
| Empagliflozin 25 MGsubjects will receive daily dose of 25mg of empagliflozin for 3 months | Drug | Treatment |
| ControlAlso: PlaceboPlacebo | Drug | control |
Primary outcome
Effect of Empagliflozin on Autonomic Nervous System
Time frame: Baseline and 12 weeks
autonomic activity will be measured with as NE turnover rate. Total-body NE turnover rate was measured with 3H-NE infusion. A prime (3.8 µCi)-continuous (0.38 µCi/min) infusion of 3H-NE was started and continued for 60 minutes. Arterialized blood samples were collected before the start and between the 40-60 minute time period after the start of 3H-NE infusion. Total body NE turnover rate was calculated as the 3H-NE infusion rate (dpm/min) divided by the steady state plasma 3H-NE specific activity (dpm/pg) after 30 minutes
1 secondary outcome
Hepatic Glucose Production
Time frame: Baseline and 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Muhammad Abdul-Ghani, MD, PhD principal investigator
Diabetes Division, UTHSCSA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Empagliflozin 25 MG in people with Hepatic Glucose Metabolism, run by The University of Texas Health Science Center at San Antonio 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 1 inclusion and 1 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 28 Aug 2024. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 28 Aug 2024). 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?
Effect of Empagliflozin on Autonomic Nervous System (time frame: Baseline and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Aug 2024.