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NCT Number: NCT05417646

Impact of SGLT2 on Glucosuria in HNF1A-MODY

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.

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Key information

Conditions

Maturity-Onset Diabetes of the Young, Type 3 Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glucose Metabolism Disorders Glycosuria Male Urogenital Diseases Metabolic Diseases Nutritional and Metabolic Diseases Type 2 Diabetes Urination Disorders Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Steno Diabetes Center Copenhagen

Herlev, 2730, Denmark

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Hyperglycaemic clamp

Other

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

Placebo

Drug

Placebo comparator to empagliflozin

Empagliflozin

Drug

Single-dose, 25 mg, two hours before clamp

Primary outcomes

  1. Urinary glucose excretion

    Time frame: Assesed during 3 hour hyperglycaemic clamp

Secondary outcomes

  1. Urinary glucose excretion adjusted for glomerular filtration rate (GFR)

    Time frame: Assesed during 3 hour hyperglycaemic clamp

    GFR: 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) plasma clearance

  2. Infused amount of glucose

    Time frame: Assesed during 3 hour hyperglycaemic clamp

  3. Urine volume

    Time frame: Assesed during 3 hour hyperglycaemic clamp

  4. Glucose tissue disposal

    Time frame: Assesed during 3 hour hyperglycaemic clamp

    difference between infused and excreted glucose

  5. Urinary creatinine clearance

    Time frame: Assesed during 3 hour hyperglycaemic clamp

    Urinary creatinine clearance calculated by plasma creatinine concentration and urinary creatinine excretion

  6. Concentration of plasma c-peptide

    Time frame: Assesed during 3 hour hyperglycaemic clamp

    Summarized as area under the curve (AUC)

  7. Concentration of plasma glucagon

    Time frame: Assesed during 3 hour hyperglycaemic clamp

    Summarized as AUC

  8. Renal threshold of glucose excretion

    Time frame: Assesed during 3 hour hyperglycaemic clamp

    Estimated using plasma glucose concentrations, urinary glucose excretion and GFR

Sponsors and collaborators

Lead sponsor

Steno Diabetes Center Copenhagen

Other

Collaborators

  • University of Copenhagen

Registry information

Acronym: MOD3ST-CLAMP

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Jun 14, 2022
Registry last updated
Jul 27, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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