Empagliflozin Effect on Glucose Toxicity

NCT03437330 | Withdrawn Phase 4

• 1 other identifier: Oxidise
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Empagliflozin effect on glucose toxicity in type 2 diabetes patients - a randomized, open-label, controlled, parallel group, exploratory study

Conditions

Type2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  12 weeks

• Change in skeletal muscle lipid peroxidation

  12 weeks

• Change in 24-hour urinary excretion rate of 8-iso PGF2a

  12 weeks

• • Difference in DNA methylation pattern

  12 weeks

• Change in plasma FFA levels

  12 weeks

Study Arms (2)

Empagliflozin (Jardiance®)

EXPERIMENTAL

Dose/frequency: 10 mg once daily for 12 weeks Route of administration: oral

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

Drug: Insulin Glargine (Lantus®)

Interventions

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)

Empagliflozin (Jardiance®)

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)

Insulin Glargine (Lantus®)

Eligibility Criteria

• Age: 40 Years - 70 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• Subjects are to be excluded from the study if they display any of the following criteria:
• 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
• 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:

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (2)

University Hospital

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

German Diabetes Center, Leibniz-Center for Diabetes Research at the Heinrich-Heine-University Duesseldorf

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

MeSH Terms

Interventions

empagliflozin; Insulin Glargine

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2017
• First Posted: February 19, 2018
• Study Start: October 27, 2021
• Primary Completion: May 3, 2023
• Study Completion: May 3, 2023
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)