Impact of SGLT2 on Glucosuria in HNF1A-MODY

Type 2 Diabetes Clinical Trial

— MOD3ST-CLAMP  

Official title:

Impact of SGLT2 on Glucosuria in HNF1A-MODY

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05417646
• Other study ID #: H-21066984
• Status: Completed
• Phase: N/A
• Start date: June 22, 2022
• Est. completion date: June 14, 2023

Study information

• Verified date: July 2023
• Source: Steno Diabetes Center Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Participants: Patients with HNF1A-MODY (n=12) and patients with T2D (n=12)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: June 14, 2023
• Est. primary completion date: June 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

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

Drug:
• Placebo
Placebo comparator to empagliflozin
• Empagliflozin
Single-dose, 25 mg, two hours before clamp

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center Copenhagen	Herlev

Sponsors (2)

Lead Sponsor	Collaborator
Steno Diabetes Center Copenhagen	University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urinary glucose excretion		Assesed during 3 hour hyperglycaemic clamp
Secondary	Urinary glucose excretion adjusted for glomerular filtration rate (GFR)	GFR: 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) plasma clearance	Assesed during 3 hour hyperglycaemic clamp
Secondary	Infused amount of glucose		Assesed during 3 hour hyperglycaemic clamp
Secondary	Urine volume		Assesed during 3 hour hyperglycaemic clamp
Secondary	Glucose tissue disposal	difference between infused and excreted glucose	Assesed during 3 hour hyperglycaemic clamp
Secondary	Urinary creatinine clearance	Urinary creatinine clearance calculated by plasma creatinine concentration and urinary creatinine excretion	Assesed during 3 hour hyperglycaemic clamp
Secondary	Concentration of plasma c-peptide	Summarized as area under the curve (AUC)	Assesed during 3 hour hyperglycaemic clamp
Secondary	Concentration of plasma glucagon	Summarized as AUC	Assesed during 3 hour hyperglycaemic clamp
Secondary	Renal threshold of glucose excretion	Estimated using plasma glucose concentrations, urinary glucose excretion and GFR	Assesed during 3 hour hyperglycaemic clamp