Clinical trial NCT03520153: Characterization of Diabetes Mellitus in Fibrous Dysplasia/McCune-Albright Syndrome
Official title: Characterization of Diabetes Mellitus in Fibrous Dysplasia/McCune-Albright Syndrome
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: McCune-Albright Syndrome
Fibrous Dysplasia
Intraductal Papillary Mucinous Neoplasm
Diabetes Mellitus
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2018-05-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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).

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Glucose tolerance status
timeFrame: Baseline
measure: Insulin sensitivity
timeFrame: Baseline
measure: Insulin secretion
timeFrame: Baseline
measure: Beta cell capacity
timeFrame: Baseline
measure: Hepatic glucose fluxes (gluconeogenesis and glycogenolysis)
timeFrame: At least 2 weeks post baseline testing
Secondary outcomes:
measure: Islet cell antibodies (ICA),
timeFrame: Baseline
measure: Glutamic acid decarboxylase antibodies (GAD65)
timeFrame: Baseline
measure: Islet antigen-2 antibodies (IA-2A)
timeFrame: Baseline
measure: Zinc transporter 8 (ZnT8)
timeFrame: Baseline
measure: Fasting lipid panel
timeFrame: Baseline
measure: Fasting incretins
timeFrame: Baseline
measure: Prandial incretins
timeFrame: Baseline
measure: Free fatty acids
timeFrame: Baseline
measure: Growth hormone
timeFrame: Baseline
measure: Insulin-like growth factor-1 (IGF-1)
timeFrame: Baseline
measure: Renal function (BUN and creatinine)
timeFrame: Baseline
measure: Hemoglobin A1c
timeFrame: Baseline
measure: Urinalysis
timeFrame: Baseline
measure: Glycerol
timeFrame: Baseline
measure: Leptin
timeFrame: Baseline
measure: Adiponectin
timeFrame: Baseline
measure: Liver function tests (AST and ALT)
timeFrame: Baseline
measure: C-reactive protein (CRP)
timeFrame: Baseline
measure: Interleukin 6 (IL-6)
timeFrame: Baseline
measure: Tumor necrosis factor alpha (TNF-alpha)
timeFrame: Baseline
Other outcomes:
measure: Maturity-Onset Diabetes of Young (MODY) genetic testing
timeFrame: Baseline
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Cemre Robinson, MD
role: PRINCIPAL_INVESTIGATOR
References: