Clinical trial NCT05417646: Impact of SGLT2 on Glucosuria in HNF1A-MODY
Official title: Impact of SGLT2 on Glucosuria in HNF1A-MODY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Maturity-Onset Diabetes of the Young, Type 3
Type 2 Diabetes
Keywords: Sodium-Glucose Transporter 2
Sodium-Glucose Transporter 2 Inhibitors
Glycosuria
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2022-06-14
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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)

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)

Primary outcomes:
measure: Urinary glucose excretion
timeFrame: Assesed during 3 hour hyperglycaemic clamp
Secondary outcomes:
measure: Urinary glucose excretion adjusted for glomerular filtration rate (GFR)
timeFrame: Assesed during 3 hour hyperglycaemic clamp
measure: Infused amount of glucose
timeFrame: Assesed during 3 hour hyperglycaemic clamp
measure: Urine volume
timeFrame: Assesed during 3 hour hyperglycaemic clamp
measure: Glucose tissue disposal
timeFrame: Assesed during 3 hour hyperglycaemic clamp
measure: Urinary creatinine clearance
timeFrame: Assesed during 3 hour hyperglycaemic clamp
measure: Concentration of plasma c-peptide
timeFrame: Assesed during 3 hour hyperglycaemic clamp
measure: Concentration of plasma glucagon
timeFrame: Assesed during 3 hour hyperglycaemic clamp
measure: Renal threshold of glucose excretion
timeFrame: Assesed during 3 hour hyperglycaemic clamp
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Tina Vilsbøll
role: PRINCIPAL_INVESTIGATOR
References: