Type2 Diabetes MellitusPhase 4NCT03437330
Empagliflozin Effect on Glucose Toxicity
A Phase 4 study testing Empagliflozin (Jardiance®) and Insulin Glargine (Lantus®) in people with Type2 Diabetes Mellitus, run by University Hospital Tuebingen at 2 sites in Germany.
Trial summary
Empagliflozin effect on glucose toxicity in type 2 diabetes patients - a randomized, open-label, controlled, parallel group, exploratory study Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Type2 Diabetes Mellitus
- What is being tested?
- Empagliflozin (Jardiance®) and Insulin Glargine (Lantus®)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesGermany
- Study dates
- 27 Oct 2021to 3 May 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must fulfill all of the following criteria before inclusion in the study:
- The informed consent form must be signed before any study specific tests or procedures are done
- Male or female patients aged between 40 and 70 years (including) at the first screening visit
- Patients diagnosed with T2DM
- HbA1c between 7-9% (including)
- Stable treatment with antidiabetic drugs over the last 4 weeks
Show all 13Show fewer
- Accepted background medication:
- Metformin up to 2000 mg per day and/or
- DPP-IV inhibitors:
- Linagliptin up to 5 mg per day Sitagliptin up to 100 mg per day Vildagliptin up to 100 mg per day Saxagliptin up to 5 mg per day
- Body mass index (BMI) between 25 and 40 kg/m2 (including)
- Ability to understand and follow study-related instructions
- No clinical relevant abnormalities during ECG and cardiac examinations
Who cannot join
- Subjects are to be excluded from the study if they display any of the following criteria:
- Unstable Angina pectoris, myocardial infarction or stroke within 1 year before inclusion in the study
- History of atrial fibrillation
- Uncontrolled arterial hypertension (> 160/100 mmHg in three subsequent measurements - mean value)
- eGFR < 60 ml/min/1.73 m2
- Macroalbuminuria defined as ≥ 300 mg albumin / 24h urine
Show all 22Show fewer
- Triglyceride > 250 mg/dl
- Genetic muscle disease
- Known coagulation disorder
- Treatment with anti-platelet therapy and anticoagulation which cannot be paused for medical reasons
- Treatment with anticoagulants within 7 days prior to the muscle biopsy
- Contraindications according to the local SmPC of Lantus® or Jardiance® (see Appendix 1)
- History of hypersensitivity to any of the study drugs or their ingredients or to drugs with similar structure or to the local anesthetic scandicaine or lidocaine
- Addiction or other diseases that preclude the patient from appropriately assessing the nature and scope as well as possible consequences of the clinical study
- Pregnant or breast-feeding women
- Women of childbearing potential unless women who meet the following criteria:
- Post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum follicle-stimulating hormone [FSH] > 40 U/mL)
- Postoperatively (six weeks after bilateral ovariectomy with or without hysterectomy)
- Regular and correct use of a contraceptive method with error rate <1% per year such as implants, depot injections, oral contraceptives or intrauterine devices
- Sexual abstinence
- Vasectomy of the partner
- Males must agree not to father a child and to refrain from donating semen or sperm while participating in the study and for 90 days following discontinuation from this study
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
German Diabetes Center, Leibniz-Center for Diabetes Research at the Heinrich-Heine-University Duesseldorf
Düsseldorf, North Rhine-Westphalia, 40225
University Hospital
Tübingen, Baden-Wurttemberg, 72076
About this study
Official title: Empagliflozin Effect on Glucose Toxicity in Type 2 Diabetes Patients - a Randomized, Open-label, Controlled, Parallel Group, Exploratory Study
Empagliflozin effect on glucose toxicity in type 2 diabetes patients - a randomized, open-label, controlled, parallel group, exploratory study
Read the detailed description
The EMPA-REG outcome trial showed that empagliflozin on top of standard therapy for Type 2 diabetes mellitus (T2DM) resulted in superiority in terms of the primary composite cardiovascular endpoint (hazard ratio (1) = 0.86; 95% confidence interval [CI] 0.74-0.99; P value = 0.04), hospitalization for heart failure (-35%), cardiovascular mortality (-38%) and all-cause mortality (-32%, each p < 0.001) (2). This reduction in mortality is not fully explained by the reduction in HbA1c, body weight, waist circumference and blood pressure in the empagliflozin groups versus the placebo group. Differences in mode of action of empagliflozin compared to standard therapy might, thus, help to explain why empagliflozin was so efficient in reducing cardiovascular death.
The aim of the present study is to provide evidence for a reduction of skeletal muscle H2O2 levels, and consequently improvement in mitochondrial function, and restored methylation pattern of key transcription factors in skeletal muscle from patients with T2DM when treated with empagliflozin versus insulin glargine as the prototypical medication favoring glucose uptake into tissues. It is hypothesized that empagliflozin compared to insulin specifically reduces H2O2 concentrations in skeletal muscle of patients with T2DM, because it leads to excretion of glucose and lower glucose uptake in skeletal muscle (22), while insulin shifts the major part of excess glucose into skeletal muscle cells.
- Conditions
- Type2 Diabetes Mellitus
- Being tested
- Empagliflozin (Jardiance®), Insulin Glargine (Lantus®)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin (Jardiance®)Drug
Empagliflozin Dose/frequency: 10 mg once daily for 12 weeks Route of administration: oral Reference group: Insulin glargine (Lantus®) Dose/frequency: see below FBG 6-7 mmol/L: +2 IU (stop when FBG is reduced by 0.5 mmol/L or documented hypoglycemia < 3.9 mmol/L occurs) FBG 7-8 mmol/L: +4 IU (stop when FBG is reduced by 1.0 mmol/L or documented hypoglycemia < 3.9 mmol/L occurs) FBG > 8 mmol/L: +6 IU (stop when FBG is reduced by 1.5 mmol/L or documented hypoglycemia < 3.9 mmol/L occurs)
Insulin Glargine (Lantus®)Drug
insulin glargine shall be titrated according to the following scheme: If FBG 6-7 mmol/L: reduce fasting glucose by 0.5 mmol/L If FBG 7-8 mmol/L: reduce fasting glucose by 0.75 mmol/L
If FBG 8-9 mmol/L: reduce fasting glucose by 1.0 mmol/L Thus, insulin glargine doses should be adapted as follows:
FBG 6-7 mmol/L: +2 IU (stop when FBG is reduced by 0.5 mmol/L or documented hypoglycemia < 3.9 mmol/L occurs) FBG 7-8 mmol/L: +3IU (stop when FBG is reduced by 0.75 mmol/L or documented hypoglycemia < 3.9 mmol/L occurs) FBG > 8 mmol/L: +5 IU (stop when FBG is reduced by 1.0mmol/L or documented hypoglycemia < 3.9 mmol/L occurs)
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin (Jardiance®) | Experimental | Dose/frequency: 10 mg once daily for 12 weeks Route of administration: oral Receives: Drug: Empagliflozin (Jardiance®) |
| Insulin Glargine (Lantus®) | Active comparator | Thus, insulin glargine doses should be adapted as follows:
FBG 6-7 mmol/L: +2 IU FBG 7-8 mmol/L: +3 IU FBG > 8 mmol/L: +5 IU Receives: Drug: Insulin Glargine (Lantus®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in skeletal muscle H202 concentration between baseline and end of treatment (EoT)
The primary objective is to investigate the change in H2O2 concentration as a read out of reactive oxygen species (ROS) production in skeletal muscle biopsies from T2DM patients before and after treatment with empagliflozin or insulin glargine.
Measured: 12 weeks
Secondary outcomes (5)
Secondary objectives of the study are to evaluate the effect of empagliflozin and insulin glargine on glucose toxicity in skeletal muscle by investigating
Change in skeletal muscle mitochondrial function (O2consumption) between baseline and EoT
Measured: 12 weeks
Change in skeletal muscle lipid peroxidation
Change in skeletal muscle lipid peroxidation between baseline and EoT
Measured: 12 weeks
Change in 24-hour urinary excretion rate of 8-iso PGF2a
Change in 24-hour urinary excretion rate of 8-iso PGF2a between baseline and EoT
Measured: 12 weeks
• Difference in DNA methylation pattern
- Difference in DNA methylation pattern between the treatment groups at EoT
Measured: 12 weeks
Change in plasma FFA levels
Change in plasma FFA levels between baseline and end of trial
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start27 Oct 2021
- Primary completion3 May 2023
- Study completion3 May 2023
Why it stopped: poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03437330
- Sponsor's protocol ID
- Oxidise
- Status last verified
- May 2024
- First submitted
- 21 Dec 2017
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Empagliflozin Effect on Glucose Toxicity in Type 2 Diabetes Patients - a Randomized, Open-label, Controlled, Parallel Group, Exploratory Study
- ClinicalTrials.gov ID
- NCT03437330
- Acronym / sponsor ID
- Oxidise
- Conditions
- Type2 Diabetes Mellitus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: poor recruitment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- 27 Oct 2021 (actual)
- Primary completion
- 3 May 2023 (actual)
- Study completion
- 3 May 2023 (actual)
- First posted
- 19 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Empagliflozin effect on glucose toxicity in type 2 diabetes patients - a randomized, open-label, controlled, parallel group, exploratory study
Detailed description
The EMPA-REG outcome trial showed that empagliflozin on top of standard therapy for Type 2 diabetes mellitus (T2DM) resulted in superiority in terms of the primary composite cardiovascular endpoint (hazard ratio (1) = 0.86; 95% confidence interval [CI] 0.74-0.99; P value = 0.04), hospitalization for heart failure (-35%), cardiovascular mortality (-38%) and all-cause mortality (-32%, each p < 0.001) (2). This reduction in mortality is not fully explained by the reduction in HbA1c, body weight, waist circumference and blood pressure in the empagliflozin groups versus the placebo group. Differences in mode of action of empagliflozin compared to standard therapy might, thus, help to explain why empagliflozin was so efficient in reducing cardiovascular death.
The aim of the present study is to provide evidence for a reduction of skeletal muscle H2O2 levels, and consequently improvement in mitochondrial function, and restored methylation pattern of key transcription factors in skeletal muscle from patients with T2DM when treated with empagliflozin versus insulin glargine as the prototypical medication favoring glucose uptake into tissues. It is hypothesized that empagliflozin compared to insulin specifically reduces H2O2 concentrations in skeletal muscle of patients with T2DM, because it leads to excretion of glucose and lower glucose uptake in skeletal muscle (22), while insulin shifts the major part of excess glucose into skeletal muscle cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin (Jardiance®) | Experimental | Drug: Empagliflozin (Jardiance®)Dose/frequency: 10 mg once daily for 12 weeks Route of administration: oral |
| Insulin Glargine (Lantus®) | Active comparator | Drug: Insulin Glargine (Lantus®)Thus, insulin glargine doses should be adapted as follows: FBG 6-7 mmol/L: +2 IU FBG 7-8 mmol/L: +3 IU FBG > 8 mmol/L: +5 IU |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- The informed consent form must be signed before any study specific tests or procedures are done
- Male or female patients aged between 40 and 70 years (including) at the first screening visit
- Patients diagnosed with T2DM
- HbA1c between 7-9% (including)
- Stable treatment with antidiabetic drugs over the last 4 weeks
Key exclusion criteria (22 listed)
- Unstable Angina pectoris, myocardial infarction or stroke within 1 year before inclusion in the study
- History of atrial fibrillation
- Uncontrolled arterial hypertension (> 160/100 mmHg in three subsequent measurements - mean value)
- eGFR < 60 ml/min/1.73 m2
- Macroalbuminuria defined as ≥ 300 mg albumin / 24h urine
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 (Jardiance®)Empagliflozin Dose/frequency: 10 mg once daily for 12 weeks Route of administration: oral Reference group: Insulin glargine (Lantus®) Dose/frequency: see below FBG 6-7 mmol/L: +2 IU (stop when FBG is reduced by 0.5 mmol/L or documented hypoglycemia < 3.9 mmol/L occurs) FBG 7-8 mmol/L: +4 IU (stop when FBG is reduced by 1.0 mmol/L or documented hypoglycemia < 3.9 mmol/L occurs) FBG > 8 mmol/L: +6 IU (stop when FBG is reduced by 1.5 mmol/L or documented hypoglycemia < 3.9 mmol/L occurs) | Drug | Empagliflozin (Jardiance®) |
| Insulin Glargine (Lantus®)insulin glargine shall be titrated according to the following scheme: If FBG 6-7 mmol/L: reduce fasting glucose by 0.5 mmol/L If FBG 7-8 mmol/L: reduce fasting glucose by 0.75 mmol/L If FBG 8-9 mmol/L: reduce fasting glucose by 1.0 mmol/L Thus, insulin glargine doses should be adapted as follows: FBG 6-7 mmol/L: +2 IU (stop when FBG is reduced by 0.5 mmol/L or documented hypoglycemia < 3.9 mmol/L occurs) FBG 7-8 mmol/L: +3IU (stop when FBG is reduced by 0.75 mmol/L or documented hypoglycemia < 3.9 mmol/L occurs) FBG > 8 mmol/L: +5 IU (stop when FBG is reduced by 1.0mmol/L or documented hypoglycemia < 3.9 mmol/L occurs) | Drug | Insulin Glargine (Lantus®) |
Primary outcome
Change in skeletal muscle H202 concentration between baseline and end of treatment (EoT)
Time frame: 12 weeks
The primary objective is to investigate the change in H2O2 concentration as a read out of reactive oxygen species (ROS) production in skeletal muscle biopsies from T2DM patients before and after treatment with empagliflozin or insulin glargine.
5 secondary outcomes
Secondary objectives of the study are to evaluate the effect of empagliflozin and insulin glargine on glucose toxicity in skeletal muscle by investigating
Time frame: 12 weeks
Change in skeletal muscle lipid peroxidation
Time frame: 12 weeks
Change in 24-hour urinary excretion rate of 8-iso PGF2a
Time frame: 12 weeks
• Difference in DNA methylation pattern
Time frame: 12 weeks
Change in plasma FFA levels
Time frame: 12 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites 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 (Jardiance®) and Insulin Glargine (Lantus®) in people with Type2 Diabetes Mellitus, run by University Hospital Tuebingen at 2 sites in Germany.
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 13 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: withdrawn, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. 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. 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?
The study was withdrawn before enrolling participants, so there are no results.
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 in skeletal muscle H202 concentration between baseline and end of treatment (EoT) (time frame: 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 16 May 2024.