Impact of SGLT2 on Glucosuria in HNF1A-MODY

NCT05417646 | Completed

• 1 other identifier: H-21066984
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Glycosuria

Outcome Measures

Primary Outcomes (1)

• Urinary glucose excretion

  Assesed during 3 hour hyperglycaemic clamp

Secondary Outcomes (8)

• Urinary glucose excretion adjusted for glomerular filtration rate (GFR)

  Assesed during 3 hour hyperglycaemic clamp

• Infused amount of glucose

  Assesed during 3 hour hyperglycaemic clamp

• Urine volume

  Assesed during 3 hour hyperglycaemic clamp

• Glucose tissue disposal

  Assesed during 3 hour hyperglycaemic clamp

• Urinary creatinine clearance

  Assesed during 3 hour hyperglycaemic clamp

Study Arms (4)

HNF1A-MODY - SGLT2 inhibition

ACTIVE COMPARATOR

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

Other: Hyperglycaemic clamp; Drug: Empagliflozin

HNF1A-MODY - Placebo

PLACEBO COMPARATOR

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

Other: Hyperglycaemic clamp; Drug: Placebo

Type 2 Diabetes - SGLT2 inhibition

ACTIVE COMPARATOR

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

Other: Hyperglycaemic clamp; Drug: Empagliflozin

Type 2 Diabetes - Placebo

PLACEBO COMPARATOR

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

Other: Hyperglycaemic clamp; Drug: Placebo

Interventions

Hyperglycaemic clamp OTHER

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

HNF1A-MODY - Placebo; HNF1A-MODY - SGLT2 inhibition; Type 2 Diabetes - Placebo; Type 2 Diabetes - SGLT2 inhibition

Placebo DRUG

Placebo comparator to empagliflozin

HNF1A-MODY - Placebo; Type 2 Diabetes - Placebo

Empagliflozin DRUG

Single-dose, 25 mg, two hours before clamp

HNF1A-MODY - SGLT2 inhibition; Type 2 Diabetes - SGLT2 inhibition

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• University of Copenhagen: collaborator

Study Sites (1)

Steno Diabetes Center Copenhagen

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

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

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Tina Vilsbøll

  Steno Diabetes Center Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2022
• First Posted: June 14, 2022
• Study Start: June 22, 2022
• Primary Completion: June 14, 2023
• Study Completion: June 14, 2023
• Last Updated: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)