search
Back to results

Impact of SGLT2 on Glucosuria in HNF1A-MODY (MOD3ST-CLAMP)

Primary Purpose

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

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Hyperglycaemic clamp
Placebo
Empagliflozin
Sponsored by
Steno Diabetes Center Copenhagen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Maturity-Onset Diabetes of the Young, Type 3 focused on measuring Sodium-Glucose Transporter 2, Sodium-Glucose Transporter 2 Inhibitors, Glycosuria

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Steno Diabetes Center Copenhagen

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

HNF1A-MODY - SGLT2 inhibition

HNF1A-MODY - Placebo

Type 2 Diabetes - SGLT2 inhibition

Type 2 Diabetes - Placebo

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

Urinary glucose excretion

Secondary Outcome Measures

Urinary glucose excretion adjusted for glomerular filtration rate (GFR)
GFR: 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) plasma clearance
Infused amount of glucose
Urine volume
Glucose tissue disposal
difference between infused and excreted glucose
Urinary creatinine clearance
Urinary creatinine clearance calculated by plasma creatinine concentration and urinary creatinine excretion
Concentration of plasma c-peptide
Summarized as area under the curve (AUC)
Concentration of plasma glucagon
Summarized as AUC
Renal threshold of glucose excretion
Estimated using plasma glucose concentrations, urinary glucose excretion and GFR

Full Information

First Posted
May 24, 2022
Last Updated
July 25, 2023
Sponsor
Steno Diabetes Center Copenhagen
Collaborators
University of Copenhagen
search

1. Study Identification

Unique Protocol Identification Number
NCT05417646
Brief Title
Impact of SGLT2 on Glucosuria in HNF1A-MODY
Acronym
MOD3ST-CLAMP
Official Title
Impact of SGLT2 on Glucosuria in HNF1A-MODY
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
June 22, 2022 (Actual)
Primary Completion Date
June 14, 2023 (Actual)
Study Completion Date
June 14, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Steno Diabetes Center Copenhagen
Collaborators
University of Copenhagen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Maturity-Onset Diabetes of the Young, Type 3, Type 2 Diabetes
Keywords
Sodium-Glucose Transporter 2, Sodium-Glucose Transporter 2 Inhibitors, Glycosuria

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HNF1A-MODY - SGLT2 inhibition
Arm Type
Active Comparator
Arm Description
3-hour hyperglycemic clamp with inhibition of SGLT2 (single-dose empagliflozin 25 mg two hours before clamp)
Arm Title
HNF1A-MODY - Placebo
Arm Type
Placebo Comparator
Arm Description
3-hour hyperglycemic clamp without inhibition of SGLT2 (placebo comparator to empagliflozin)
Arm Title
Type 2 Diabetes - SGLT2 inhibition
Arm Type
Active Comparator
Arm Description
3-hour hyperglycemic clamp with inhibition of SGLT2 (single-dose empagliflozin 25 mg two hours before clamp)
Arm Title
Type 2 Diabetes - Placebo
Arm Type
Placebo Comparator
Arm Description
3-hour hyperglycemic clamp without inhibition of SGLT2 (placebo comparator to empagliflozin)
Intervention Type
Other
Intervention Name(s)
Hyperglycaemic clamp
Intervention Description
Three-hour, three-step glucose clamp with plasma glucose targets 10, 14 and 18 mmol/l (each one hour)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo comparator to empagliflozin
Intervention Type
Drug
Intervention Name(s)
Empagliflozin
Intervention Description
Single-dose, 25 mg, two hours before clamp
Primary Outcome Measure Information:
Title
Urinary glucose excretion
Time Frame
Assesed during 3 hour hyperglycaemic clamp
Secondary Outcome Measure Information:
Title
Urinary glucose excretion adjusted for glomerular filtration rate (GFR)
Description
GFR: 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) plasma clearance
Time Frame
Assesed during 3 hour hyperglycaemic clamp
Title
Infused amount of glucose
Time Frame
Assesed during 3 hour hyperglycaemic clamp
Title
Urine volume
Time Frame
Assesed during 3 hour hyperglycaemic clamp
Title
Glucose tissue disposal
Description
difference between infused and excreted glucose
Time Frame
Assesed during 3 hour hyperglycaemic clamp
Title
Urinary creatinine clearance
Description
Urinary creatinine clearance calculated by plasma creatinine concentration and urinary creatinine excretion
Time Frame
Assesed during 3 hour hyperglycaemic clamp
Title
Concentration of plasma c-peptide
Description
Summarized as area under the curve (AUC)
Time Frame
Assesed during 3 hour hyperglycaemic clamp
Title
Concentration of plasma glucagon
Description
Summarized as AUC
Time Frame
Assesed during 3 hour hyperglycaemic clamp
Title
Renal threshold of glucose excretion
Description
Estimated using plasma glucose concentrations, urinary glucose excretion and GFR
Time Frame
Assesed during 3 hour hyperglycaemic clamp

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tina Vilsbøll
Organizational Affiliation
Steno Diabetes Center Copenhagen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Steno Diabetes Center Copenhagen
City
Herlev
ZIP/Postal Code
2730
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Impact of SGLT2 on Glucosuria in HNF1A-MODY

We'll reach out to this number within 24 hrs