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

NCT03520153 | Withdrawn

• 1 other identifier: 2000022658
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

McCune-Albright Syndrome; Fibrous Dysplasia; Intraductal Papillary Mucinous Neoplasm; Diabetes Mellitus

Outcome Measures

Primary Outcomes (5)

• 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

• Insulin sensitivity

  This primary outcome will be obtained from the oral glucose tolerance test

  Baseline

• Insulin secretion

  This primary outcome will be obtained from the hyperglycemic clamp

  Baseline

• 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

• 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 Outcomes (20)

• Islet cell antibodies (ICA),

  Baseline

• Glutamic acid decarboxylase antibodies (GAD65)

  Baseline

• Islet antigen-2 antibodies (IA-2A)

  Baseline

• Zinc transporter 8 (ZnT8)

  Baseline

• Fasting lipid panel

  Baseline

Other Outcomes (1)

• Maturity-Onset Diabetes of Young (MODY) genetic testing

  Baseline

Study Arms (5)

FD/MAS with diabetes mellitus

Fibrous Dysplasia/McCune-Albright Syndrome with diabetes mellitus. Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Procedure: Hyperinsulinemic Euglycemic Clamp and 2H20; Procedure: Hyperglycemic Clamp; Diagnostic Test: Oral Glucose Tolerance Test

FD/MAS without diabetes mellitus

Fibrous Dysplasia/McCune-Albright Syndrome without diabetes mellitus. Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Procedure: Hyperinsulinemic Euglycemic Clamp and 2H20; Procedure: Hyperglycemic Clamp; Diagnostic Test: Oral Glucose Tolerance Test

FD/MAS without diabetes and without IPMN

Fibrous Dysplasia/McCune-Albright Syndrome without diabetes mellitus and without intraductal papillary mucinous neoplasms. Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Procedure: Hyperinsulinemic Euglycemic Clamp and 2H20; Procedure: Hyperglycemic Clamp; Diagnostic Test: Oral Glucose Tolerance Test

FD/MAS without diabetes and with IPMN

Fibrous Dysplasia/McCune-Albright Syndrome without diabetes mellitus and with intraductal papillary mucinous neoplasms. Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Procedure: Hyperinsulinemic Euglycemic Clamp and 2H20; Procedure: Hyperglycemic Clamp; Diagnostic Test: Oral Glucose Tolerance Test

Healthy Controls

Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Procedure: Hyperinsulinemic Euglycemic Clamp and 2H20; Procedure: Hyperglycemic Clamp; Diagnostic Test: Oral Glucose Tolerance Test

Interventions

Hyperinsulinemic Euglycemic Clamp and 2H20 PROCEDURE

Test is used to assess insulin effects on hepatic glucose production.

FD/MAS with diabetes mellitus; FD/MAS without diabetes and with IPMN; FD/MAS without diabetes and without IPMN; FD/MAS without diabetes mellitus; Healthy Controls

Hyperglycemic Clamp PROCEDURE

Test of beta-cell function and insulin secretion. Involves increasing and maintaining blood glucose concentration with IV variable infusion of dextrose.

FD/MAS with diabetes mellitus; FD/MAS without diabetes and with IPMN; FD/MAS without diabetes and without IPMN; FD/MAS without diabetes mellitus; Healthy Controls

Oral Glucose Tolerance Test DIAGNOSTIC_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.

FD/MAS with diabetes mellitus; FD/MAS without diabetes and with IPMN; FD/MAS without diabetes and without IPMN; FD/MAS without diabetes mellitus; Healthy Controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will include adult Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) subjects (\> 18 years-old) with diabetes, without diabetes, with and without intraductal papillary mucinous neoplasms (IPMNs). FD/MAS subjects, who are enrolled in the National Institutes of Health (NIH) Natural History Study and who have already been screened with an MRI of the abdomen or magnetic resonance cholangiopancreatography for pancreatic lesions, will be invited to participate in the current study based on an existing diagnosis of diabetes and/or IPMNs. In addition, seven adult healthy volunteers will be screened and recruited by the investigator from Yale Center for Clinical Investigation (YCCI) Recruitment Database.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Fibrous Dysplasia, Polyostotic; Fibrous Dysplasia of Bone; Diabetes Mellitus

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Cemre Robinson, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: May 9, 2018
• Study Start: August 7, 2018
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: September 4, 2019

Record last verified: 2019-07

Locations

US (1)