Impact of SGLT2 on Glucosuria in HNF1A-MODY
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Urinary glucose excretion
Study Overview
Brief Summary
Maturity onset diabetes of the young (MODY) is a subtype of diabetes which is caused by mutations in specific genes leading to diabetes. The most common cause of MODY is due to mutations in the gene hepatocyte nuclear factor 1 alpha (HNF1A) and is consequently named HNF1A-MODY (or MODY3). HNF1A-MODY is associated with urinary excretion of glucose at lower blood glucose levels compared to other types of diabetes. Normally, glucose is reabsorbed by sodium-glucose cotransporter 2 (SGLT2), but SGLT2 is downregulated due to the mutation in HNF1A. Investigators aim to evaluate the impact of the decreased expression of SGLT2 on glucosuria in patients with HNF1A-MODY compared to patients with type 2 diabetes (T2D) using a single dose of an SGLT2 inhibitor during a glucose clamp experiment.
Detailed Description
Participants: Patients with HNF1A-MODY (n=12) and patients with T2D (n=12)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥18 years
- •HNF1A-MODY verified by genetic testing (only patients with HNF1A-MODY)
- •Type 2 diabetes diagnosis according to World Health Organization (only patients with type 2 diabetes)
- •Treatment with diet and/or a glucose-lowering drug (only patients with HNF1A-MODY)
- •Normal haemoglobin (males 8.3-10.5 mmol/l, females 7.3-9.5 mmol/l)
- •Informed consent
Exclusion Criteria
- •Nephropathy (estimated GFR <60 ml/min/1.73m2 and/or albuminuria)
- •Known significant liver disease and/or plasma alanine aminotransferase (ALT) and/or plasma aspartate aminotransferase (AST) above 2 × normal values)
- •Pregnancy or breastfeeding
- •Treatment with SGLT2 inhibitor
- •Fasting plasma glucose > 10 mmol/l
- •Family history of HNF1A-MODY (only patients with type 2 diabetes)
Arms & Interventions
HNF1A-MODY - SGLT2 inhibition
3-hour hyperglycemic clamp with inhibition of SGLT2 (single-dose empagliflozin 25 mg two hours before clamp)
Intervention: Hyperglycaemic clamp (Other)
HNF1A-MODY - SGLT2 inhibition
3-hour hyperglycemic clamp with inhibition of SGLT2 (single-dose empagliflozin 25 mg two hours before clamp)
Intervention: Empagliflozin (Drug)
HNF1A-MODY - Placebo
3-hour hyperglycemic clamp without inhibition of SGLT2 (placebo comparator to empagliflozin)
Intervention: Hyperglycaemic clamp (Other)
HNF1A-MODY - Placebo
3-hour hyperglycemic clamp without inhibition of SGLT2 (placebo comparator to empagliflozin)
Intervention: Placebo (Drug)
Type 2 Diabetes - SGLT2 inhibition
3-hour hyperglycemic clamp with inhibition of SGLT2 (single-dose empagliflozin 25 mg two hours before clamp)
Intervention: Hyperglycaemic clamp (Other)
Type 2 Diabetes - SGLT2 inhibition
3-hour hyperglycemic clamp with inhibition of SGLT2 (single-dose empagliflozin 25 mg two hours before clamp)
Intervention: Empagliflozin (Drug)
Type 2 Diabetes - Placebo
3-hour hyperglycemic clamp without inhibition of SGLT2 (placebo comparator to empagliflozin)
Intervention: Hyperglycaemic clamp (Other)
Type 2 Diabetes - Placebo
3-hour hyperglycemic clamp without inhibition of SGLT2 (placebo comparator to empagliflozin)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Urinary glucose excretion
Time Frame: Assesed during 3 hour hyperglycaemic clamp
Secondary Outcomes
- Concentration of plasma c-peptide(Assesed during 3 hour hyperglycaemic clamp)
- Glucose tissue disposal(Assesed during 3 hour hyperglycaemic clamp)
- Concentration of plasma glucagon(Assesed during 3 hour hyperglycaemic clamp)
- Renal threshold of glucose excretion(Assesed during 3 hour hyperglycaemic clamp)
- Urinary glucose excretion adjusted for glomerular filtration rate (GFR)(Assesed during 3 hour hyperglycaemic clamp)
- Urine volume(Assesed during 3 hour hyperglycaemic clamp)
- Urinary creatinine clearance(Assesed during 3 hour hyperglycaemic clamp)
- Infused amount of glucose(Assesed during 3 hour hyperglycaemic clamp)