McCune-Albright SyndromeNCT03520153
Characterization of Diabetes Mellitus in Fibrous Dysplasia/McCune-Albright Syndrome
An observational study of McCune-Albright Syndrome and Fibrous Dysplasia, run by Yale University at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- McCune-Albright Syndrome, Fibrous Dysplasia, Intraductal Papillary Mucinous Neoplasm
- What is being tested?
- Hyperinsulinemic Euglycemic Clamp and 2H20, Hyperglycemic Clamp and Oral Glucose Tolerance Test
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Aug 2018to Aug 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale New Haven Hospital
New Haven, Connecticut, 06510
About this study
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).
Read the 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:
- Establish the etiology of diabetes in FD/MAS
- Increase understanding of the role of IPMNs in pathogenesis of diabetes
- Provide critical insights into the pathogenesis of diabetes in FD/MAS
- Conditions
- McCune-Albright Syndrome, Fibrous Dysplasia, Intraductal Papillary Mucinous Neoplasm, Diabetes Mellitus
- Being tested
- Hyperinsulinemic Euglycemic Clamp and 2H20, Hyperglycemic Clamp, Oral Glucose Tolerance Test
- Medical subject headings
- Fibrous Dysplasia, Polyostotic, Fibrous Dysplasia of Bone, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperinsulinemic Euglycemic Clamp and 2H20Procedure or surgery
Test is used to assess insulin effects on hepatic glucose production.
Hyperglycemic ClampProcedure or surgery
Test of beta-cell function and insulin secretion. Involves increasing and maintaining blood glucose concentration with IV variable infusion of dextrose.
Oral Glucose Tolerance TestDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Procedure: Hyperinsulinemic Euglycemic Clamp and 2H20; Procedure: Hyperglycemic Clamp; Diagnostic Test: Oral Glucose Tolerance Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline
Insulin sensitivity
This primary outcome will be obtained from the oral glucose tolerance test
Measured: Baseline
Insulin secretion
This primary outcome will be obtained from the hyperglycemic clamp
Measured: 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.
Measured: 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
Measured: At least 2 weeks post baseline testing
Secondary outcomes (20)
Islet cell antibodies (ICA),
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Glutamic acid decarboxylase antibodies (GAD65)
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Islet antigen-2 antibodies (IA-2A)
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Zinc transporter 8 (ZnT8)
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Fasting lipid panel
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Fasting incretins
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Prandial incretins
Peripheral blood draw at the end of the oral glucose tolerance test
Measured: Baseline
Free fatty acids
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Growth hormone
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Insulin-like growth factor-1 (IGF-1)
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Renal function (BUN and creatinine)
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Hemoglobin A1c
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Urinalysis
Will be obtained at baseline before the start of oral glucose tolerance test to look for albuminuria
Measured: Baseline
Glycerol
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Leptin
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Adiponectin
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Liver function tests (AST and ALT)
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
C-reactive protein (CRP)
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Interleukin 6 (IL-6)
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Tumor necrosis factor alpha (TNF-alpha)
Peripheral blood draw before the start of oral glucose tolerance test
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2018
- Study start7 Aug 2018 (estimated)
- Primary completionAug 2021 (estimated)
- Study completionAug 2021 (estimated)
Why it stopped: The principal investigator is leaving Yale University and will not be continuing the work at her new institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for McCune-Albright SyndromeStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cemre Robinson, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03520153
- Sponsor's protocol ID
- 2000022658
- Status last verified
- Jul 2019
- First submitted
- 26 Apr 2018
- Last updated
- 4 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Diabetes Mellitus in Fibrous Dysplasia/McCune-Albright Syndrome
- ClinicalTrials.gov ID
- NCT03520153
- Acronym / sponsor ID
- 2000022658
- Conditions
- McCune-Albright Syndrome, Fibrous Dysplasia, Intraductal Papillary Mucinous Neoplasm, Diabetes Mellitus
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: The principal investigator is leaving Yale University and will not be continuing the work at her new institution.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 7 Aug 2018 (estimated)
- Primary completion
- Aug 2021 (estimated)
- Study completion
- Aug 2021 (estimated)
- First posted
- 9 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Establish the etiology of diabetes in FD/MAS
- Increase understanding of the role of IPMNs in pathogenesis of diabetes
- Provide critical insights into the pathogenesis of diabetes in FD/MAS
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| FD/MAS with diabetes mellitus | – | Procedure: Hyperinsulinemic Euglycemic Clamp and 2H20, Procedure: Hyperglycemic Clamp, Diagnostic Test: Oral Glucose Tolerance TestFibrous 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. |
| FD/MAS without diabetes mellitus | – | Procedure: Hyperinsulinemic Euglycemic Clamp and 2H20, Procedure: Hyperglycemic Clamp, Diagnostic Test: Oral Glucose Tolerance TestFibrous 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. |
| FD/MAS without diabetes and without IPMN | – | Procedure: Hyperinsulinemic Euglycemic Clamp and 2H20, Procedure: Hyperglycemic Clamp, Diagnostic Test: Oral Glucose Tolerance TestFibrous 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. |
| FD/MAS without diabetes and with IPMN | – | Procedure: Hyperinsulinemic Euglycemic Clamp and 2H20, Procedure: Hyperglycemic Clamp, Diagnostic Test: Oral Glucose Tolerance TestFibrous 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. |
| Healthy Controls | – | Procedure: Hyperinsulinemic Euglycemic Clamp and 2H20, Procedure: Hyperglycemic Clamp, Diagnostic Test: Oral Glucose Tolerance TestParticipants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- Must be diagnosed based on clinical grounds and/or mutation testing on bone and/or affected tissue
- Must be at least 18 years old
Key exclusion criteria (7 listed)
- Unwilling to fully cooperate with the evaluation
- Unable to provide informed consent
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperinsulinemic Euglycemic Clamp and 2H20Test is used to assess insulin effects on hepatic glucose production. | Procedure or surgery | 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 ClampTest of beta-cell function and insulin secretion. Involves increasing and maintaining blood glucose concentration with IV variable infusion of dextrose. | Procedure or surgery | 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 TestThe 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. | Diagnostic test | 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 |
Primary outcome
Glucose tolerance status
Time frame: Baseline
An oral glucose tolerance test will be performed to assess glucose tolerance status to determine if subjects have pre-IGT, IGT or diabetes
Insulin sensitivity
Time frame: Baseline
This primary outcome will be obtained from the oral glucose tolerance test
Insulin secretion
Time frame: Baseline
This primary outcome will be obtained from the hyperglycemic clamp
Beta cell capacity
Time frame: Baseline
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.
Hepatic glucose fluxes (gluconeogenesis and glycogenolysis)
Time frame: At least 2 weeks post baseline testing
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
20 secondary outcomes
Islet cell antibodies (ICA),
Time frame: Baseline
Glutamic acid decarboxylase antibodies (GAD65)
Time frame: Baseline
Islet antigen-2 antibodies (IA-2A)
Time frame: Baseline
Zinc transporter 8 (ZnT8)
Time frame: Baseline
Fasting lipid panel
Time frame: Baseline
Fasting incretins
Time frame: Baseline
Prandial incretins
Time frame: Baseline
Free fatty acids
Time frame: Baseline
Growth hormone
Time frame: Baseline
Insulin-like growth factor-1 (IGF-1)
Time frame: Baseline
Renal function (BUN and creatinine)
Time frame: Baseline
Hemoglobin A1c
Time frame: Baseline
Urinalysis
Time frame: Baseline
Glycerol
Time frame: Baseline
Leptin
Time frame: Baseline
Adiponectin
Time frame: Baseline
Liver function tests (AST and ALT)
Time frame: Baseline
C-reactive protein (CRP)
Time frame: Baseline
Interleukin 6 (IL-6)
Time frame: Baseline
Tumor necrosis factor alpha (TNF-alpha)
Time frame: Baseline
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2019.
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Fibrous Dysplasia, McCune-Albright Syndrome Patient Registry
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cemre Robinson, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of McCune-Albright Syndrome and Fibrous Dysplasia, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 4 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glucose tolerance status (time frame: Baseline). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2019.