EnVision CF Multicenter Study of Glucose Tolerance in Cystic Fibrosis

NCT03650712 | Completed DMC FDA Device

• 1 other identifier: 201809715
• Study Type: interventional
• Target: 317
• Locations: 1 country
• Sites: 4

Brief Summary

Cystic Fibrosis Related Diabetes has been identified by the CF community as one of the top ten priorities for CF research. In CF clinical decline due to dysglycemia begins early, prior to diagnosis of diabetes and increases mortality from pulmonary disease. There is presently no way to determine who, of those with dysglycemia, will experience clinical compromise. However, the CF Center in Milan has found that measurable age- and sex-dependent variables on oral glucose tolerance testing (OGTT) predict β-cell failure-the primary driver of decline in CF. the investigators propose a multi-center trial to develop nomograms of age and sex dependent reference values for OGTT-derived measures including glucose, insulin, c-peptide, and the resultant OGTT-derived estimates of β-cell function, β cell sensitivity to glucose, and oral glucose insulin sensitivity (OGIS) and to determine correlation of these with clinical status (FEV-1, BMI z score, number of pulmonary exacerbations over the past 12 months). In a subset of the cohort the investigators will perform additional studies to determine possible mechanisms driving abnormal β cell function, including the role of lean body mass (as measured by DXA), impact of incretin (GLP-1, GIP) and islet hormones (glucagon, pancreatic polypeptide) on β cell function and the relationship of reactive hypoglycemia and catecholamine responses to β cell function, as well as the relationship of β cell sensitivity to glucose as determined by our model to abnormalities in blood glucose found in a period of free living after the study (determined by continuous glucose monitoring measures (Peak glucose, time spent \>200 mg/dl, standard deviation). the investigators will also develop a biobank of stored samples to allow expansion to the full cohort if warranted and to enable future studies of dysglycemia and diabetes in CF. the investigator's eventual goal is utilization of the nomograms to determine the minimum number of measures to accurately predict risk for clinical decline from dysglycemia in CF.

Conditions

Cystic Fibrosis-related Diabetes

Keywords

cystic fibrosis; insulin; glucose; children; abnormal glucose tolerance; impaired glucose tolerance; indeterminate glycemia; diabetes

Outcome Measures

Primary Outcomes (2)

• age- and sex-based nomograms for beta cell glucose sensitivity

  The primary endpoint is relationship of beta cell sensitivity to glucose to age. To assess the primary endpoint, the following method will be used: Quantiles of beta-cell glucose sensitivity will be calculated using quantile regression. The outcome variable of the quantile curve is beta-cell glucose sensitivity (continuous, picomol per minute-1 per meter-2 per millimole-1) and the predictor variable is age (continuous, years). On the basis of the available data, we expect a linear relationship between beta-cell glucose sensitivity and age with no heteroskedasticy

  the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months

• age- and sex-based nomograms for OGIS (oral glucose insulin sensitivity)

  The primary outcome of this study is to establish age- and sex-based nomograms ("growth charts") ranging from the 5th-95th % for OGIS (oral glucose insulin sensitivity)

  the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months

Secondary Outcomes (12)

• evaluate the relationships between age and sex-based quantiles for beta cell glucose sensitivity and BMI Z-score

  data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months

• evaluate the relationships between age and sex-based quantiles for beta cell glucose sensitivity and FEV-1

  the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months

• evaluate the relationships between age and sex-based quantiles for beta cell glucose sensitivity and pulmonary exacerbations in the previous 12 months

  the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months

• evaluate the relationships between age and sex-based quantiles for OGIS and BMI z-score

  the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months

• evaluate the relationships between age and sex-based quantiles for OGIS and FEV-1

  the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months

Other Outcomes (15)

• the correlation between fat mass and fat free mass as determined by DXA and beta cell function as measured by beta cell sensitivity to glucose

  the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months

• Determine whether the area under the curve (AUC) for GLP-1 is a significant predictor of beta cell glucose sensitivity

  the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months

• Determine whether the area under the curve (AUC) for GIP is a significant predictor of beta cell glucose sensitivity

  the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months

Study Arms (4)

frequently sampled oral glucose tolerance testing

OTHER

frequently sampled oral glucose tolerance testing will be performed in a one-time cross sectional visit

Diagnostic Test: Oral glucose tolerance test

Frequently sampled oral glucose tolerance testing anc CGM

OTHER

frequently sampled oral glucose tolerance testing will be performed in a one-time cross sectional visit + continuous glucose monitor will be placed after the visit and mailed back

Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Continuous glucose monitoring

frequently sampled oral glucose tolerance testing and DXA

OTHER

frequently sampled oral glucose tolerance testing will be performed in a one-time cross sectional visit + a DXA scan will be done at the same visit

Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Dexa scan

frequently sampled oral glucose tolerance testing, CGM & DXA

OTHER

frequently sampled oral glucose tolerance testing will be performed in a one-time cross sectional visit + continuous glucose monitor will be placed after the visit and mailed back + a DXA scan will be done at the same visit

Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Continuous glucose monitoring; Diagnostic Test: Dexa scan

Interventions

Oral glucose tolerance test DIAGNOSTIC_TEST

oral glucose solution is given by mouth, blood is drawn prior to the administration of the oral glucose beverage and then at timed intervals afterward. This is the standard test to diagnosis cystic fibrosis related diabetes mellitus. However, this study will have more time points than standard screening for cystic fibrosis related diabetes mellitus

Frequently sampled oral glucose tolerance testing anc CGM; frequently sampled oral glucose tolerance testing; frequently sampled oral glucose tolerance testing and DXA; frequently sampled oral glucose tolerance testing, CGM & DXA

Continuous glucose monitoring DIAGNOSTIC_TEST

a device is placed on the subject's arm that continuously monitors subcutaneous glucose levels for up to 10 days

Also known as: CGM, CGMS

Frequently sampled oral glucose tolerance testing anc CGM; frequently sampled oral glucose tolerance testing, CGM & DXA

Dexa scan DIAGNOSTIC_TEST

low dose x-rays are used to measure the subject's bone density. This is the standard test to diagnose osteoporosis

Also known as: DXA, DEXA

frequently sampled oral glucose tolerance testing and DXA; frequently sampled oral glucose tolerance testing, CGM & DXA

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>/= 6 years
• Diagnosis of cystic fibrosis
• CF patients regularly attending the CF centers
• Clinically stable in previous 3wks:
• absence of major clinical events including pulmonary exacerbations,
• no change in their habitual treatment regimen including introduction of antibiotics or steroids in the past 3 weeks

You may not qualify if:

• Diagnosis of type 1 diabetes, type 2 diabetes, or MODY
• Organ transplantation
• new diagnosis of CFRD in the past 6 months
• antidiabetic treatment in past 6 mos (insulin or oral hypoglycemic agents)
• patients with previous CFRD diagnosis, but not currently taking insulin/glucose-lowering medications for at least 6 months should be included
• pulmonary exacerbation associated with systemic steroid requirement in the last 6 months
• on CFTR corrector less than 6 months prior to enrollment

Sponsors & Collaborators

• Katie Larson Ode: lead

Study Sites (4)

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University St. Louis

St Louis, Missouri, 63110, United States

Location

Related Publications (3)

• Battezzati A, Bedogni G, Zazzeron L, Mari A, Battezzati PM, Alicandro G, Bertoli S, Colombo C. Age- and Sex-Dependent Distribution of OGTT-Related Variables in a Population of Cystic Fibrosis Patients. J Clin Endocrinol Metab. 2015 Aug;100(8):2963-71. doi: 10.1210/jc.2015-1512. Epub 2015 Jun 9.

  PMID: 26057180 BACKGROUND

• Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ. A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care. 2001 Mar;24(3):539-48. doi: 10.2337/diacare.24.3.539.

  PMID: 11289482 BACKGROUND

• Mari A, Ferrannini E. Beta-cell function assessment from modelling of oral tests: an effective approach. Diabetes Obes Metab. 2008 Nov;10 Suppl 4:77-87. doi: 10.1111/j.1463-1326.2008.00946.x.

  PMID: 18834435 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis; Insulin Resistance; Glucose Intolerance; Diabetes Mellitus

Interventions

Glucose Tolerance Test; Continuous Glucose Monitoring; Absorptiometry, Photon

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperglycemia; 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; Monitoring, Physiologic; Radiography; Diagnostic Imaging; Densitometry; Photometry; Chemistry Techniques, Analytical

Study Officials

• Katie Larson Ode, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor Pediatric Endocrinology & Diabetes

Study Record Dates

• First Submitted: July 18, 2018
• First Posted: August 29, 2018
• Study Start: July 1, 2019
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)