Sodium-glucose cotransporter-2 inhibition and renal oxygenation in type 1 diabetes

Phase 1

• Conditions: Type 1 diabetes; MedDRA version: 21.1Level: LLTClassification code 10045228Term: Type I diabetes mellitusSystem Organ Class: 100000004861; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2019-004557-92-DK
• Lead Sponsor: Steno Diabetes Center Copenhagen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-01-02
• Last Update Posted: 17 May 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Inclusion criteria healthy controls:
•Written informed consent must be provided before participation
•Male or female patients >18 years of age with a diagnosis of type 1 diabetes (WHO criteria)
•Capable of lying in a MR-scanner for two hours

Inclusion criteria persons with type 1 diabetes:
•Written informed consent must be provided before participation
•Male or female patients >18 years of age with a diagnosis of type 1 diabetes (WHO criteria)
•Urinary albumin creatinine ratio (UACR) =30 mg/g in 2 out of 3 consecutive samples (albuminuria) prior to randomization assessed from electronic laboratory database.
•Capable of lying in a MR-scanner for two hours

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Exclusion criteria for all:
• Non-diabetic kidney disease as indicated by medical history and/or laboratory findings
• Renal failure (eGFR<15 ml/min/1.73m2), dialysis or kidney transplantation
• Treatment with beta-blocking medication
• Uncontrolled arrhythmia, 2. or 3. degree AV-block or sick sinus syndrome - assessed from a standard 12-lead electrocardiogram
• Pregnancy or breastfeeding (urine HCG is performed on all fertile women)
• Systolic blood pressure < 90 or > 200 mmHg
• Patients who, in the judgement of the investigator, is incapable of participating
• Exclusion criteria for MRI
o Claustrophobia
o Known heart disease
o Known lung disease
o Have had surgery the past six weeks
o Have foreign bodies of metal in the body (e.g. pacemaker, metal plates, metal screws)
• Exclusion criteria for arterial blood gas sampling
o Absent pulse
o Raynauds syndrome
o Buergers Disease (thromboangiitis obliterans)
o Inadequate or interrupted circulation
o Anticoagulation treatment
o Coagulopathies (hypo or hyper coagulable states)
o Arterial atherosclerosis
o Insufficient collateral perfusion
o Partial or full thickness burns over the cannulation site
o Synthetic arterial or vascular grafts or infection at the proposed site of cannulation

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary aim of the study is to assess the acute effects of SGLT2 inhibition on parameters reflecting oxygenation and oxygen consumption of the human kidney in persons with type 1 diabetes. ;Secondary Objective: Exploratory aims are to investigate acute changes in oxygen availability and oxygen access to the kidneys after SGLT2i. This include measures of peripheral blood oxygenation, mitochondrial function and autonomic function.;Primary end point(s): Primary end-point<br>•Renal oxygenation (T2*)<br>;Timepoint(s) of evaluation of this end point: 3 hours from intervention and 6 hours from intervention

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Exploratory end-points<br>•Renal cortical and medullary perfusion<br>•Renal artery flow<br>•Renal oxygen consumption<br>•Peripheral capillary oxygen saturation (SpO2)<br>•Arterial blood gasses<br>oArterial blood oxygen partial pressure (PaO2)<br>oArterial blood oxygen saturation (SaO2)<br>•Peripheral Blood Monocyte mitochondrial function<br>•Circulating inflammatory markers<br>•Baroreflex sensitivity<br>;Timepoint(s) of evaluation of this end point: 3 hours and 6 hours from intervention: Renal cortical and medullary perfusion, Renal artery flow, Renal oxygen consumption, Peripheral capillary oxygen saturation (SpO2), Arterial blood gasses, Arterial blood oxygen partial pressure (PaO2), Arterial blood oxygen saturation (SaO2)<br><br>12 hours from intervention: Peripheral Blood Monocyte mitochondrial function, Circulating inflammatory markers, Baroreflex sensitivity