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

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus; Chronic Kidney Diseases; PreDiabetes; Overweight and Obesity
• Intervention / Treatment: Behavioral: Therapeutic carbohydrate restriction combined with an SGLT-2-Inhibitor

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stefan Scherr, MDMD; Phone Number: +431 49150 2605; Email: stefan.scherr@gesundheitsverbund.at
• Study Contact Backup: Name: Marcus D Säemann, MD; Phone Number: +431 49150 2605; Email: marcus.saemann@gesundheitsverbund.at

Study Locations

• Austria
  • Vienna, Austria, 1160
    • Recruiting
    • 6th Medical Department with Nephrology and Dialysis, Clinik Ottakring
    • Contact: Stefan Scherr, MD; Phone Number: +43 1 49150 2605; Email: stefan.scherr@gesundheitsverbund.at
    • Contact: Marcus D Säemann, MD; Phone Number: +43 1 49150 2605; Email: marcus.saemann@gesundheitsverbund.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional Arm; 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; 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.
No Intervention: Control Arm; 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?

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

Collaborators and Investigators

• Sponsor: Department of Nephrology Clinic Ottakring Vienna
• Investigators: Principal Investigator: Stefan Scherr, MD, 6th Medical Department with Nephrology and Dialysis, Clinik Ottakring, Vienna, Austria

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2023
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: October 6, 2023
• First Submitted That Met QC Criteria: October 16, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Low Carbohydrate Diet; Carbohydrate Restriction; SGLT-2-Inhibitors
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Overnutrition; Nutrition Disorders; Body Weight; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Overweight; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: PRAGMATICS-Pilot

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No