Evaluation of Dapagliflozin and Lifestyle Intervention on Complication Risk in Prediabetes with Early Chronic Kidney Disease: A Randomized, Placebo-Controlled Trial
- Trial ID
- 2024-512179-11-00
- Protocol
- Lifetime
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate whether **kidney damage** can be improved in patients with early-stage chronic kidney disease (CKD stage G1A2/G2A2) and prediabetes through the administration of SGLT2 inhibitor, Dapagliflozin, in addition to lifestyle interventions. This is clinically relevant as it addresses the potential for therapeutic intervention to mitigate renal complications in a population at risk for progression to more severe kidney disease.
Participants
The clinical trial involves participants diagnosed with **early stage of chronic kidney disease** (CKD stage G1A2/G2A2) and prediabetes. The study population includes male, female, and intersex individuals aged between 35 and 75 years. Participants are selected based on their assignment to high-risk diabetes clusters 3, 5, and 6, as per Wagner et al., 2021, and must exhibit signs of early kidney disease, such as a urinary albumin-to-creatinine ratio (uACR) between 30 mg/g and 300 mg/g. Prediabetes is defined by fasting glucose levels greater than 100 mg/dL, HbA1c levels above 5.6, or 2-hour OGTT glucose levels exceeding 140 mg/dL. Participants are required to have a body mass index (BMI) of at least 20 kg/m² and normal thyroid-stimulating hormone (TSH) levels. The trial includes individuals on stable thyroid replacement therapy and antihypertensive medication regimens. The sponsor has not provided information regarding the total number of participants. The trial population was selected with consideration for their ability to understand and follow study-related instructions, and all participants must have signed an informed consent document. The study does not include individuals if their participation poses an unacceptable risk to their safety or well-being, as determined by the investigator.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **dapagliflozin**, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, in improving kidney damage in patients with early-stage chronic kidney disease (CKD stage G1A2/G2A2) and prediabetes. This study is a randomized, placebo-controlled, double-blind, multi-center trial. Participants will be randomly assigned to receive either dapagliflozin 10 mg daily or a matching placebo, in addition to lifestyle counseling, for a duration of one year. The primary endpoint is the improvement of kidney damage as indicated by albuminuria levels.
The trial will commence with a screening visit to assess eligibility based on specific inclusion criteria, such as age between 35 and 75 years, presence of prediabetes, and early signs of kidney disease. Participants must also have a stable treatment regimen for any existing thyroid or antihypertensive medications. Following successful screening, eligible participants will be enrolled and randomized into the treatment or placebo group. Study visits will occur at regular intervals to monitor safety, adherence, and efficacy outcomes, with assessments including laboratory tests and physical examinations.
The expected duration of participant involvement is approximately 12 months, with the possibility of early termination if any safety concerns arise or if the participant withdraws consent. The trial is anticipated to conclude by October 2027, with recruitment starting in January 2024. The end-of-study visit will involve a comprehensive evaluation to assess the primary and any secondary endpoints, ensuring the collection of final data for analysis.
Treatment
The clinical trial involves the administration of **Dapagliflozin**, an antidiabetic medication, as the experimental treatment. Dapagliflozin is provided in the form of a **film-coated tablet** and is administered orally. The dosage is set at a maximum of 10 mg per day, with a total maximum dose of 3650 mg over the course of the study. The treatment period is limited to 12 months. Participants are required to take the medication daily, and compliance is monitored through regular assessments. The primary objective of the trial is to evaluate the effect of Dapagliflozin on kidney damage in patients with prediabetes.
The study also includes a **placebo** group, which receives a placebo matching Dapagliflozin. The placebo is designed to mimic the appearance of the Dapagliflozin tablets but contains no active pharmaceutical ingredients. The placebo is administered in the same manner as the experimental medication, ensuring that the study remains double-blind. Participants in the placebo group follow the same dosing schedule and compliance monitoring as those receiving Dapagliflozin. This allows for a controlled comparison to assess the efficacy of the experimental treatment.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the improvement of kidney damage in patients with **chronic kidney disease (CKD)** stage G1A2/G2A2 and prediabetes. The primary endpoint is the reduction of albuminuria, which will be measured to determine the effectiveness of the treatment with the SGLT2 inhibitor dapagliflozin (10 mg/day) in conjunction with lifestyle counseling, compared to placebo and lifestyle counseling over a one-year period. The trial will involve a randomized, placebo-controlled, multi-center design to ensure robust and reliable results. The efficacy assessments will focus on the changes in urinary albumin-to-creatinine ratio (uACR) as a key indicator of kidney function improvement. The trial is designed to provide comprehensive data on the potential benefits of dapagliflozin in reducing kidney damage in the specified patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male, female or intersexualpatients aged between 35 and 75 years (including)
- Prediabetes (defined by one of the following: FG ≥ 100 mg/dL or 2h OGTT glucose ≥ 140mg/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 treatmentregimen for at least 3 months prior to the screening visit (V-1)
- Patients who are receiving antihypertensive medication such as mineralocorticoidreceptor antagonists must be on a stable treatment regimen for at least 6 weeks prior tothe screening visit (V-1)
- Patients who are treated antihypertensive medication such as ACE inhibitors and AT1receptor antagonists, thiazides as well as loop diuretics must be on stable treatment forat least 2 weeks
- Understand and voluntarily sign an informed consent document prior to any studyrelated 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
Exclusion Criteria
- 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 empagliflozinor any other SGLT2-Inhibitor)
- Symptomatic chronic congestive heart disease
- New diuretic or antihypertensive medication or dosing changes within the last 2 weeks, foraldosterone antagonists within the last 6 weeks
- known or suspected orthostatic proteinuria
- any acute severe or chronic severe illness, including the following: malignant disease ongoingor < 5 years ago, unstable cardiovascular disease or procedure within 3 months prior toenrolment or expected to require coronary revascularisation procedure
- history of or current therapy for congestive heart failure (NYHA III and IV), pacemaker oraortic 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 pyloricstenosis
- relevant hepatic disease, including, but not limited to, acute hepatitis, chronic activehepatitis, or severe hepatic insufficiency, including patients with alanine aminotransferaseand/or aspartate aminotransferase > 3 x upper limit of normal and/or total bilirubin (TB) > 2mg/dL (> 34.2 μmol/L) (patients with TB > 2 mg/dL [> 34.2 μmol/L] and documented Gilbert’ssyndrome 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 new intake of antidepressant or antipsychotic agents(start within last 3 months)
- Positive Screening for a severe depression (BDI ≥29)
- history of hypersensitivity to the study drug or its ingredients
- more than 5% weight loss in the last 3 months
- Pregnant or breastfeeding women
- Subject (male, female or intersexual) is not willing to use highly effective contraceptivemethods during treatment and for 14 days (male or female) after the end of treatment(highly effective methods are defined as: combined hormonal contraception associated withinhibition of ovulation, progestogen-only hormonal contraception associated with inhibitionof ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubalocclusion, vasectomized partner, sexual abstinence)
- Current participation in other interventional clinical trials or treatment with other IMPswithin five times the half-life of the drug
- Previous therapy with dapagliflozin or other drugs that can potentially lead to overlappingtoxicities 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 whileparticipating in this clinical trial
- Patients will not be included in the study if, in the opinion of the investigator, participationleads to an unacceptable risk to their safety and well-being
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 15 Jan 2024 | 182 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo matching Dapagliflozin | Placebo | N/A | — | — | — | N/A |
Dapagliflozin Ascend 10 mg Filmtabletten | Test | FILMTABLETTEN | ORAL USE | 10 | 12 | PRD11219972 |