Mauriac Syndrome: Isotopic Techniques and Genetic Analysis

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus; Short Stature; Glycogen Deposition
• Intervention / Treatment: Other: oral glucose load; Other: exercise test

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.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1205
    • Not yet recruiting
    • Geneva University Hospital
    • Contact: Karim Gariani, MD; Email: karim.gariani@hcuge.ch
    • Principal Investigator: Karim Gariani, MD
    • Sub-Investigator: Philippe Klee, MD
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Recruiting
      • Lausanne University Hospitals
      • Contact: Christel F Tran, MD; Phone Number: +41213143680; Email: christel.tran@chuv.ch
      • Principal Investigator: Christel Tran, MD
      • Principal Investigator: Anne Wojtusciszyn, MD
      • Principal Investigator: Despina Pavlidou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Mauriac syndrome; 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.	Other: oral glucose load; oral glucose load (60g) followed by exercise at fixed wattage (60W) for 30 min; Other: exercise test; oral glucose load (60g) followed by exercise at fixed wattage (60W) for 30 min
Other: Type 1 diabetes mellitus; 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.	Other: oral glucose load; oral glucose load (60g) followed by exercise at fixed wattage (60W) for 30 min; Other: exercise test; oral glucose load (60g) followed by exercise at fixed wattage (60W) for 30 min

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Time -90 minutes to Time 360 minutes
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.	Time -90 minutes to Time 360 minutes
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.	Time -90 minutes to Time 360 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At inclusion period

Collaborators and Investigators

• Sponsor: University of Lausanne
• Collaborators: University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2022
• Primary Completion (Actual): July 31, 2022
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: February 12, 2020
• First Submitted That Met QC Criteria: February 14, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Developmental; Dwarfism
• Other Study ID Numbers: NCT2019-01755

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No