Treating Patients With Renal Impairment and Altered Glucose MetAbolism With TherapeutIc Carbohydrate Restriction and Sglt2-Inhibiton - a Pilot Study

Study Overview
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Brief Summary
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This randomized controlled trail will evaluate the efficacy and safety of a simultaneous therapeutic carbohydrate restriction and treatment with the Sodium-Glucose-Transporter-2-Inhibitor dapagliflozin in comparison to the standard of care treatment in patients with chronic kidney disease and prediabetes or type 2 diabetes mellitus. Participants will be randomized 1:1. The interventional group will be educated on how to implement a therapeutic carbohydrate restriction (50-100 grams of carbohydrates per day). Regarding safety, the patients of the interventional group will be provided with continuous glucose monitoring systems and blood ketone meters. The participants of the control group will continue to receive the standard of care therapy for the treatment of chronic kidney disease and prediabetes or type 2 diabetes mellitus. Both groups will be treated with dapagliflozin.

Official Title
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Treating Patients With Renal Impairment and Altered Glucose MetAbolism With TherapeutIc Carbohydrate Restriction and Sglt2-Inhibiton - a Pilot Study

Conditions
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Chronic Kidney Diseases, Diabetes Mellitus, PreDiabetes, Overweight and Obesity

Intervention / Treatment
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* Behavioral: Therapeutic carbohydrate restriction combined with an SGLT-2-Inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic Kidney Disease Stage KDIGO 3a-4 (eGFR eGFR 25-59 mg/min/1.73m²) Prediabetes or Diabetes according to the Guideline of the American Diabetes Association (HbA1c >5,7 percent, or fasting glucose values > 100 mg/dL, or glucose levels > 140 mg/dL at 2h during an oral glucose tolerance test) Being overweight (Body Mass Index > 25.0 kg/m²) Being able to independently: - Perform measurements of blood glucose and ketone levels - Use a continous glucose monitor - Contact the study team Exclusion Criteria: Patients who are allergic to SGLT-2-Inhibitors Patients with autoimmune diabetes (Typ 1 or LADA) Patients with pancreoprivic diabetes Patients with a history of ketoacidosis or lactate acidosis Patients with severe hypoglycemic episodes in the 6 moths prior to inclusion Patients with bariatric surgery (in the past or planed) Patients with nephritic range proteinuria (>3,5g of Albumin/day) Patients with active malignant diseases Pregnant or breastfeeding patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional Arm<br>The patients randomized to the interventional Arm will be simultaneously treated with therapeutic carbohydrate restriction and dapagliflozin for a period of three months. During this time repeated measurements of blood ketone levels and a continuous glucose monitoring will be performed. | Behavioral: Therapeutic carbohydrate restriction combined with an SGLT-2-Inhibitor<br>* The patients will be educated on how to implement a therapeutic carbohydrate restriction, which consists of 50 to 130 grams of carbohydrate per day, simultaneously they will continue to receive the SGLT-2-Inhibitor dapagliflozin.<br>|
| No Intervention: Control Arm<br>The patients randomized to the control arm will continue to receive the standard of care for chronic kidney disease and prediabetes or diabetes, which includes the use of dapagliflozin. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in HbA1c | Primary endpoint is difference in HbA1c after 3 months in the interventional group | after 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | Body composition will be measured with a body composition monitoring device before and after the study period | after 3 Months | 
| Body weight | Body weight will be measured before and after the study period | after 3 Months | 
| Serum creatinine | Serum creatinine will be measured before and after the study period | after 3 Months | 
| Serum Cystatin C | Serum Cystatin C will be measured before and after the study period | after 3 Months | 
| Albuminuria | Albuminuria will be measured before and after the study period | after 3 Months | 
| Oral glucose tolerance | Oral glucose tolerance will be assessed using a 75g oral glucose tolerance test before and after the study period | after 3 Months | 
| Glucose variability | Glucose variability will be assessed using continuous glucose monitor | during the 3 Months of the study period | 
| Time in range | Time in range regarding glucose will be assessed using continuous glucose monitor | during the 3 Months of the study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low Carbohydrate Diet, Carbohydrate Restriction, SGLT-2-Inhibitors