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Mauriac Syndrome: Isotopic Techniques and Genetic Analysis

Primary Purpose

Diabetes Mellitus, Short Stature, Glycogen Deposition

Status

Recruiting

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

oral glucose load

exercise test

About this trial

This is an interventional other trial for Diabetes Mellitus

Eligibility Criteria

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

Inclusion Criteria:

Inclusion criteria for controls:
DT1
> 18 years old)
Presence of at least one of the following auto-antibodies: anti-GAD65, anti-IAA, anti-ZnT8, anti-IA2 or ICA and/or low C-Peptide
Insulin therapy by multiple daily injections or continuous subcutaneous insulin infusion by an insulin pump
Informed consent as documented by signature

Inclusion criteria for subjects:

Mauriac syndrome
DT1
> 18 years old
Presence of hepatomegaly in infancy (confirmed ≥ 1 abdominal US) at the time of diagnosis of Mauriac Syndrome
Presence of short stature during infancy at the time of diagnosis of Mauriac Syndrome (<P3; WHO growth curves on ≥ 2 different measures, at 2 different time-points)
Presence of at least one of the following auto-antibodies: anti-GAD65, anti-IAA, anti-ZnT8, anti-IA2 or ICA and/or low C-Peptide
Informed consent as documented by signature

Exclusion criteria for subjects and controls :

Obesity (BMI ≥ 30 kg/m2 or > 90th percentile)
Illness that contraindicates physical activity
Women who are pregnant or breast feeding
Any clinically unstable disease
Myocardial infarcts, syncope, heart rhythm disorder, unstable hypertension in the last 6 months
Blood donation in the last 3 months for men and 4 months for women before the study
Enrollment in a previous study less than 30 days before the start of the study
Participation of the investigator, a family member, an employee or someone having a link with the investigator

Sites / Locations

Lausanne University HospitalsRecruiting
Geneva University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Mauriac syndrome

Type 1 diabetes mellitus

Arm Description

An oral dose of glucose (labelled with 1% U-13C6-glucose) will be given at time 0 min followed by a 30-min cycling exercise at time 300 min.

Outcomes

Primary Outcome Measures

In vivo kinetics of ingested glucose

Plasma glucose kinetics [Time -90 min before ingestion of a test meal to Time 360 min after ingestion of a test meal] Baseline : [Time -90min to Time 0min] After an oral glucose load (60g): [Time 0min to Time 300min] During exercise at fixed wattage (60W) for 30 min: [Time 300 min to Time 330 min] After exercise for 30 min [Time 330 min to Time 360 min] Trial stable isotope tracers ([U-13C6] glucose ingestion, will be used to assess ingested glucose flux at baseline and during the test.

In vivo kinetics of endogenous glucose

Plasma glucose kinetics [Time -90 min before ingestion of a test meal to Time 360 min after ingestion of a test meal] Baseline : [Time -90min to Time 0min] After an oral glucose load (60g): [Time 0min to Time 300min] During exercise at fixed wattage (60W) for 30 min: [Time 300 min to Time 330 min] After exercise for 30 min [Time 330 min to Time 360 min] Trial stable isotope tracers [6,6-2H2] glucose infusion will be used to assess endogenous glucose flux at baseline and during the test.

In vivo kinetics of lactate

Plasma lactate kinetics [Time -90 min before ingestion of a test meal to Time 360 min after ingestion of a test meal] Baseline : [Time -90min to Time 0min] After an oral glucose load (60g): [Time 0min to Time 300min] During exercise at fixed wattage (60W) for 30 min: [Time 300 min to Time 330 min] After exercise for 30 min [Time 330 min to Time 360 min] Trial stable isotope tracers [1-13C1]lactate infusion will be used to assess lactate flux at baseline and during the test.

Secondary Outcome Measures

DNA Banking

10 ml of whole blood will be collected, at baseline, in two tubes EDTA 5ml for DNA extraction and banking in view of next generation sequencing (NGS) analysis.

Full Information

NCT ID

NCT04275141

First Posted

February 12, 2020

Last Updated

April 4, 2023

Sponsor

University of Lausanne

Collaborators

University Hospital, Geneva

1. Study Identification

Unique Protocol Identification Number

NCT04275141

Brief Title

Mauriac Syndrome: Isotopic Techniques and Genetic Analysis

Official Title

Genetic Analysis Coupled to Application of Isotopic Techniques to the Study of Mauriac Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 17, 2022 (Actual)

Primary Completion Date

July 31, 2022 (Actual)

Study Completion Date

December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Lausanne

Collaborators

University Hospital, Geneva

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Mauriac syndrome (MS) is an entity of individuals combining poorly controlled diabetes mellitus type 1, short stature and glycogenic hepatopathy. Thus, the functional significance of Mauriac syndrome for glucose metabolism remains disputed, and whether genetic defects in glycogen metabolism contribute to glycogenic hepatopathy in MS remains to be clarified.Coupling the genetic analysis of targeted genes involved in glucose regulation with a dynamic exploration will eventually determine if a genetic abnormality leads to the disease and explains the nature of the phenotype.

Detailed Description

Investigation of glucose homeostasis in MS, after an oral glucose load followed by exercise, using a quantitative measurement of the substrate flux. This dynamic in vivo kinetics can be explored using stable, nonradioactive tracers with the help of gas or liquid chromatography. Investigation of genetic factors associated with MS phenotype. Molecular analysis will be performed by next generation sequencing (exome or whole genome sequencing). In addition, a targeted analysis for pathogenic variants in genes implicated in homeostasis regulation will be done.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Short Stature, Glycogen Deposition

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Case control study

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Mauriac syndrome

Arm Type

Other

Arm Description

An oral dose of glucose (labelled with 1% U-13C6-glucose) will be given at time 0 min followed by a 30-min cycling exercise at time 300 min.

Arm Title

Type 1 diabetes mellitus

Arm Type

Other

Arm Description

An oral dose of glucose (labelled with 1% U-13C6-glucose) will be given at time 0 min followed by a 30-min cycling exercise at time 300 min.

Intervention Type

Other

Intervention Name(s)

oral glucose load

Intervention Description

oral glucose load (60g) followed by exercise at fixed wattage (60W) for 30 min

Intervention Type

Other

Intervention Name(s)

exercise test

Intervention Description

oral glucose load (60g) followed by exercise at fixed wattage (60W) for 30 min

Primary Outcome Measure Information:

Title

In vivo kinetics of ingested glucose

Description

Time Frame

Time -90 minutes to Time 360 minutes

Title

In vivo kinetics of endogenous glucose

Description

Plasma glucose kinetics [Time -90 min before ingestion of a test meal to Time 360 min after ingestion of a test meal] Baseline : [Time -90min to Time 0min] After an oral glucose load (60g): [Time 0min to Time 300min] During exercise at fixed wattage (60W) for 30 min: [Time 300 min to Time 330 min] After exercise for 30 min [Time 330 min to Time 360 min] Trial stable isotope tracers [6,6-2H2] glucose infusion will be used to assess endogenous glucose flux at baseline and during the test.

Time Frame

Time -90 minutes to Time 360 minutes

Title

In vivo kinetics of lactate

Description

Time Frame

Time -90 minutes to Time 360 minutes

Secondary Outcome Measure Information:

Title

DNA Banking

Description

10 ml of whole blood will be collected, at baseline, in two tubes EDTA 5ml for DNA extraction and banking in view of next generation sequencing (NGS) analysis.

Time Frame

At inclusion period

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Inclusion criteria for controls: DT1 > 18 years old) Presence of at least one of the following auto-antibodies: anti-GAD65, anti-IAA, anti-ZnT8, anti-IA2 or ICA and/or low C-Peptide Insulin therapy by multiple daily injections or continuous subcutaneous insulin infusion by an insulin pump Informed consent as documented by signature Inclusion criteria for subjects: Mauriac syndrome DT1 > 18 years old Presence of hepatomegaly in infancy (confirmed ≥ 1 abdominal US) at the time of diagnosis of Mauriac Syndrome Presence of short stature during infancy at the time of diagnosis of Mauriac Syndrome (<P3; WHO growth curves on ≥ 2 different measures, at 2 different time-points) Presence of at least one of the following auto-antibodies: anti-GAD65, anti-IAA, anti-ZnT8, anti-IA2 or ICA and/or low C-Peptide Informed consent as documented by signature Exclusion criteria for subjects and controls : Obesity (BMI ≥ 30 kg/m2 or > 90th percentile) Illness that contraindicates physical activity Women who are pregnant or breast feeding Any clinically unstable disease Myocardial infarcts, syncope, heart rhythm disorder, unstable hypertension in the last 6 months Blood donation in the last 3 months for men and 4 months for women before the study Enrollment in a previous study less than 30 days before the start of the study Participation of the investigator, a family member, an employee or someone having a link with the investigator

Facility Information:

Facility Name

Lausanne University Hospitals

City

Lausanne

State/Province

Vaud

ZIP/Postal Code

1011

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christel F Tran, MD

Phone

+41213143680

christel.tran@chuv.ch

First Name & Middle Initial & Last Name & Degree

Christel Tran, MD

First Name & Middle Initial & Last Name & Degree

Anne Wojtusciszyn, MD

First Name & Middle Initial & Last Name & Degree

Despina Pavlidou, MD

Facility Name

Geneva University Hospital

City

Geneva

ZIP/Postal Code

1205

Country

Switzerland

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Karim Gariani, MD

karim.gariani@hcuge.ch

First Name & Middle Initial & Last Name & Degree

Karim Gariani, MD

First Name & Middle Initial & Last Name & Degree

Philippe Klee, MD

12. IPD Sharing Statement

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Mauriac Syndrome: Isotopic Techniques and Genetic Analysis

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