Characterization of Diabetes Mellitus in Fibrous Dysplasia/McCune-Albright Syndrome

Diabetes Mellitus Clinical Trial

Official title:

Characterization of Diabetes Mellitus in Fibrous Dysplasia/McCune-Albright Syndrome

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03520153
• Other study ID #: 2000022658
• Status: Withdrawn
• Start date: August 7, 2018
• Est. completion date: August 2021

Study information

• Verified date: July 2019
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators' objective is to understand the pathogenesis of diabetes mellitus in Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) by: 1) establishing the contributions of insulin resistance versus impaired insulin secretion, 2) investigating presence of excess glucagon signaling by measuring gluconeogenesis and glycogenolysis, and 3) investigating a potential interaction between diabetes and intraductal papillary mucinous neoplasms (IPMNs).

Description:

Specific project aims include:

Aim 1: Determine insulin secretion and sensitivity in subjects with MAS-associated diabetes.

Aim 2: Measure gluconeogenesis and glycogenolysis in MAS-associated diabetes to investigate a potential role for excess glucagon signaling.

Aim 3: Determine if IPMN development is associated with impairment of insulin secretion prior to development of overt diabetes.

The authors expect that this study will:

1. Establish the etiology of diabetes in FD/MAS

2. Increase understanding of the role of IPMNs in pathogenesis of diabetes

3. Provide critical insights into the pathogenesis of diabetes in FD/MAS

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2021
• Est. primary completion date: August 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) group:

• Must be diagnosed based on clinical grounds and/or mutation testing on bone and/or affected tissue

Control group:

• Must be at least 18 years old

Exclusion Criteria:

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) group:

• Unwilling to fully cooperate with the evaluation

• Unable to provide informed consent

Control group:

• History of diabetes, insulin resistance, pancreatic disease, pancreatic cysts or amylase/lipase abnormality

• Use of any type of oral diabetes medications and/or insulin

• Unable to provide informed consent

Related Conditions & MeSH terms

• Diabetes Mellitus
• Fibrous Dysplasia
• Fibrous Dysplasia of Bone
• Intraductal Papillary Mucinous Neoplasm
• McCune-Albright Syndrome
• Syndrome

Intervention

Procedure:
• Hyperinsulinemic Euglycemic Clamp and 2H20
Test is used to assess insulin effects on hepatic glucose production.
• Hyperglycemic Clamp
Test of beta-cell function and insulin secretion. Involves increasing and maintaining blood glucose concentration with IV variable infusion of dextrose.

Diagnostic Test:
• Oral Glucose Tolerance Test
The oral glucose tolerance test (OGTT) measures the body's ability to use a type of sugar, called glucose, that is the body's main source of energy. An OGTT can be used to diagnose prediabetes and diabetes.

Locations

Country	Name	City	State
United States	Yale New Haven Hospital	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maturity-Onset Diabetes of Young (MODY) genetic testing	The test detects deletions in the HNF4A, GCK, HNF1A, HNF1B genes and mutations in the HNF4A, GCK, HNF1A, HNF1B and IPF1. Will be obtained at baseline before the start of oral glucose tolerance test only in those subjects with an existing diagnosis of diabetes mellitus.	Baseline
Primary	Glucose tolerance status	An oral glucose tolerance test will be performed to assess glucose tolerance status to determine if subjects have pre-IGT, IGT or diabetes	Baseline
Primary	Insulin sensitivity	This primary outcome will be obtained from the oral glucose tolerance test	Baseline
Primary	Insulin secretion	This primary outcome will be obtained from the hyperglycemic clamp	Baseline
Primary	Beta cell capacity	AIRmax stimulation test during the hyperglycemic clamp to ascertain the maximal acute insulin response (AIR) to arginine, which is a measure of functional beta cell capacity.	Baseline
Primary	Hepatic glucose fluxes (gluconeogenesis and glycogenolysis)	Measurements from the Hyperinsulinemic Euglycemic Clamp/ 2H20 Study will be used to assess insulin effects on hepatic glucose production and glycerol kinetics isotopes and the deuterium enrichment at carbons 2 and 5 (C2 and C5) of plasma glucose providing information on glucose fluxes	At least 2 weeks post baseline testing
Secondary	Islet cell antibodies (ICA),	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Glutamic acid decarboxylase antibodies (GAD65)	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Islet antigen-2 antibodies (IA-2A)	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Zinc transporter 8 (ZnT8)	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Fasting lipid panel	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Fasting incretins	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Prandial incretins	Peripheral blood draw at the end of the oral glucose tolerance test	Baseline
Secondary	Free fatty acids	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Growth hormone	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Insulin-like growth factor-1 (IGF-1)	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Renal function (BUN and creatinine)	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Hemoglobin A1c	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Urinalysis	Will be obtained at baseline before the start of oral glucose tolerance test to look for albuminuria	Baseline
Secondary	Glycerol	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Leptin	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Adiponectin	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Liver function tests (AST and ALT)	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	C-reactive protein (CRP)	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Interleukin 6 (IL-6)	Peripheral blood draw before the start of oral glucose tolerance test	Baseline
Secondary	Tumor necrosis factor alpha (TNF-alpha)	Peripheral blood draw before the start of oral glucose tolerance test	Baseline