Impact of SGLT2 on Glucosuria in HNF1A-MODY

NCT ID: NCT05417646

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-22
• Study Completion Date: 2023-06-14

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)

Conditions

Maturity-Onset Diabetes of the Young, Type 3; Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

HNF1A-MODY - SGLT2 inhibition

3-hour hyperglycemic clamp with inhibition of SGLT2 (single-dose empagliflozin 25 mg two hours before clamp)

Group Type: ACTIVE_COMPARATOR

Hyperglycaemic clamp

Intervention Type: OTHER

Three-hour, three-step glucose clamp with plasma glucose targets 10, 14 and 18 mmol/l (each one hour)

Empagliflozin

Intervention Type: DRUG

Single-dose, 25 mg, two hours before clamp

HNF1A-MODY - Placebo

3-hour hyperglycemic clamp without inhibition of SGLT2 (placebo comparator to empagliflozin)

Group Type: PLACEBO_COMPARATOR

Hyperglycaemic clamp

Intervention Type: OTHER

Three-hour, three-step glucose clamp with plasma glucose targets 10, 14 and 18 mmol/l (each one hour)

Placebo

Intervention Type: DRUG

Placebo comparator to empagliflozin

Type 2 Diabetes - SGLT2 inhibition

3-hour hyperglycemic clamp with inhibition of SGLT2 (single-dose empagliflozin 25 mg two hours before clamp)

Group Type: ACTIVE_COMPARATOR

Hyperglycaemic clamp

Intervention Type: OTHER

Three-hour, three-step glucose clamp with plasma glucose targets 10, 14 and 18 mmol/l (each one hour)

Empagliflozin

Intervention Type: DRUG

Single-dose, 25 mg, two hours before clamp

Type 2 Diabetes - Placebo

3-hour hyperglycemic clamp without inhibition of SGLT2 (placebo comparator to empagliflozin)

Group Type: PLACEBO_COMPARATOR

Hyperglycaemic clamp

Intervention Type: OTHER

Three-hour, three-step glucose clamp with plasma glucose targets 10, 14 and 18 mmol/l (each one hour)

Placebo

Intervention Type: DRUG

Placebo comparator to empagliflozin

Interventions

Hyperglycaemic clamp

Three-hour, three-step glucose clamp with plasma glucose targets 10, 14 and 18 mmol/l (each one hour)

Intervention Type: OTHER

Placebo

Placebo comparator to empagliflozin

Intervention Type: DRUG

Empagliflozin

Single-dose, 25 mg, two hours before clamp

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Copenhagen

OTHER

Sponsor Role: collaborator

Steno Diabetes Center Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tina Vilsbøll

Role: PRINCIPAL_INVESTIGATOR

Steno Diabetes Center Copenhagen

Locations

Steno Diabetes Center Copenhagen

Herlev, , Denmark

Countries

Denmark

Other Identifiers

H-21066984

Identifier Type: -

Identifier Source: org_study_id