Mauriac Syndrome: Isotopic Techniques and Genetic Analysis

NCT04275141 | Completed

• 1 other identifier: NCT2019-01755
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

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.

Conditions

Diabetes Mellitus; Short Stature; Glycogen Deposition

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• DNA Banking

  At inclusion period

Study Arms (2)

Mauriac syndrome

OTHER

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; Other: exercise test

Type 1 diabetes mellitus

OTHER

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; Other: exercise test

Interventions

oral glucose load OTHER

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

Mauriac syndrome; Type 1 diabetes mellitus

exercise test OTHER

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

Mauriac syndrome; Type 1 diabetes mellitus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Lausanne: lead
• University Hospital, Geneva: collaborator

Study Sites (2)

Lausanne University Hospitals

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Geneva University Hospital

Geneva, 1205, Switzerland

Location

MeSH Terms

Conditions

Diabetes Mellitus; Dwarfism

Interventions

Exercise Test

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Case control study

Study Record Dates

• First Submitted: February 12, 2020
• First Posted: February 19, 2020
• Study Start: January 17, 2022
• Primary Completion: July 31, 2022
• Study Completion: December 30, 2023
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

CH (2)