SGLT2-Hemmung in Verbindung mit Lebensstilintervention und die Auswirkung auf das Risiko für Komplikationen bei Subtypen von PatientInnen mit Prädiabetes - eine randomisierte, placebokontrollierte, multizentrische Studie
- Conditions
- The study will include adult male and female patients with an early stage of chronic kidney disease (CKD stage G1A2/G2A2) and prediabetesTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2021-005721-25-DE
- Lead Sponsor
- niveristy Hospital Tuebingen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 182
••Male, female or intersexual diverse patients aged 35 and 75 years (including)
•Patients assigned to high risk for diabetes clusters 3, 5 and 6 according to Wagner et al., 2021 who have signs of early kidney disease (urinary albumin-to-creatinine ratio (uACR) 30mg/g - 300 mg/g, CKD stage G1A2/G2A2)
•Prediabetes (defined by one of the following: FG > 100 mg/dL, HbA1c > 5,6 or 2h OGTT glucose > 140 mg/dL)
•BMI = 20 kg/m2
•TSH within normal range
•Ability to understand and follow study-related instructions
•Negative pregnancy test for premenopausal women (blood)
•Patients who are receiving thyroid replacement therapy must be on a stable treatment (i.e. TSH within normal range) regimen for at least 3 months prior to the screening visit (V-10)
•Patients who are receiving antihypertensive medication such as mineralocorticoid receptor antagonists must be on a stable treatment regimen (i.e. no hospital admission due to excessive hypertension and stable dosing) for at least 6 weeks prior to the screening visit (V-10)
•Patients who are treated with antihypertensive medication such as ACE inhibitors and AT1 receptor antagonists, thiazides as well as loop diuretics must be on stable treatment (i.e. no hospital admission due to excessive hypertension and stable dosing) for at least 2 weeks
•Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
•Patients will not be included in the study if, in the opinion of the investigator, participation will lead to an unacceptable risk to the subjects’ safety or well-being
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 169
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13
••Manifest diabetes mellitus
•eGFR (as calculated by the CKD-EPI equation) < 60 ml/min/1.73 m2
•all glucose altering medications (including current therapy with dapagliflozin or empagliflozin or any other SGLT2-Inhibitor)
•Symptomatic chronic congestive heart disease
•New diuretic or antihypertensive medication or dosing changes within the last 2 weeks, for aldosterone antagonists within the last 6 weeks
•known or suspected orthostatic proteinuria
•any acute severe or chronic severe illness, including the following: malignant disease ongoing or < 5 years ago, unstable cardiovascular disease or procedure within 3 months prior to enrolment or expected to require coronary revascularisation procedure
•history of or current therapy for congestive heart failure (NYHA III and IV), pacemaker or aortic stenosis > II°
•acute pancreatic disease (i.e. elevated lipase 3x ULN)
•rapidly progressing renal disease or anuria
•known HIV infection or positive HIV test at screening
•history of or planned organ transplantation
•history or presence of inflammatory bowel disease or other severe gastrointestinal diseases, particularly those which may impact gastric emptying, such as gastroparesis or pyloric stenosis
•relevant hepatic disease, including, but not limited to, acute hepatitis, chronic active hepatitis, or severe hepatic insufficiency, including patients with alanine aminotransferase and/or aspartate aminotransferase > 3 x upper limit of normal and/or total bilirubin (TB) > 2 mg/dL (> 34.2 µmol/L) (patients with TB > 2 mg/dL [> 34.2 µmol/L] and documented Gilbert’s syndrome will be allowed to participate).
•treatment with glucocorticoids
•antibiotic treatment within the last 4 weeks
•History of ketoacidosis
•history of repeated urogenital infection
•hemoglobinopathies, haemolytic anaemia, or chronic anaemia (haemoglobin concentration < 12.0 g/dL)
•presence of psychiatric disorder or intake of antidepressant or antipsychotic agents
•Positive Screening for a severe depression (BDI =29)
•history of hypersensitivity to the study drug or its ingredients
•allergy to iodine contrast dye
•more than 5% weight loss in the last 3 months
•Pregnant or breastfeeding women
•Subject (male, female or intersexualdiverse) is not willing to use highly effective contraceptive methods during treatment and for 14 days (male or female) after the end of treatment (highly effective methods are defined as: combined hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence).
•Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the trial participant and that the vasectomized partner has received medical assessment of the surgical success.
•Current participation in other interventional clinical trials or treatment with other IMPs within five times the half-life of the drug
•Previous therapy with dapagliflozin or other drugs that can potentially lead to overlapping toxicities within five times the half-life of the drug
•Patients who do not want to be informed about accidental findings
•Any other clinical condition that would jeopardize subjects’ safety or well-being while participating in this clinical trial
•Patients will not be included in the study if, in the opinion
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to test if kidney damage can be improved;Secondary Objective: •Reduction in estimated glomerular filtration rate (eGFR) and measured GFR (mGFR) as well as slopes over time of eGFR and mGFR <br>•insulin secretion and insulin sensitivity<br>•progress to T2DM as defined as a HbA1c = 6.5<br>•remission of prediabetes as defined by HbA1c <5.7 % and in the oGTT a fasting glucose <100 mg/dl and 2 h glucose <140 mg/dl<br>•body weight, body mass index (BMI) and body composition<br>•resolution of CKD<br>•arterial blood pressure<br>•left ventricular mass index and systolic and diastolic myocardial function<br>;Primary end point(s): mean of baseline-adjusted uACR measurements (V2-V6) with dapagliflozin in comparison to treatment with placebo;Timepoint(s) of evaluation of this end point: mean of baseline-adjusted uACR measurements (V2-V6) with dapagliflozin in comparison to treatment with placebo
- Secondary Outcome Measures
Name Time Method Secondary end point(s): mean of baseline-adjusted uACR measurements (V2-V6) with dapagliflozin in comparison to treatment with placebo;Timepoint(s) of evaluation of this end point: mean of baseline-adjusted uACR measurements (V2-V6) with dapagliflozin in comparison to treatment with placebo