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Glycemic Characterization and Pancreatic Imaging Correlates in Cystic Fibrosis

Completed
Conditions
Cystic Fibrosis-related Diabetes
Cystic Fibrosis Liver Disease
Hepatic Steatosis
Cystic Fibrosis
Pancreatic Steatosis
Interventions
Device: Frequently Sampled Oral Glucose Tolerance Test and CGM
Radiation: MRI Pancreas and Liver
Registration Number
NCT03961516
Lead Sponsor
University Hospitals Cleveland Medical Center
Brief Summary

The purpose of this study is to investigate the utility of a continuous glucose monitor device (CGM) in screening for cystic fibrosis related diabetes. The investigators will also study how fat deposition in the pancreas and liver impacts insulin production and response, as measured by a frequently sampled oral glucose tolerance test.

Detailed Description

Cystic Fibrosis Related Diabetes (CFRD) occurs in 20% of adolescents and 30-40% of adults with cystic fibrosis. CFRD is associated with reduced lung function, lower body mass index, and increased mortality. The CF Foundation recommends yearly Oral Glucose Tolerance Test (OGTT) for all CF patients beginning at age 10 years. Unfortunately adherence to screening recommendations is poor, with fewer than 50% of the eligible CF patients completing OGTT each year. Additionally, the OGTT has been criticized for poor reproducibility and for not accurately reflecting real-life glycemic excursions.

The FreeStyle Libre Pro is a blinded CGM that can record up to 14 days of home-living glucose data on one sensor. This quarter-sized device is placed on the upper arm and requires no fingerstick calibrations. Multiple studies have demonstrated the utility of CGM in CF patients, but no study has determined the utility of CGM in replicating the results of an OGTT. The use of CGM in CFRD screening has the potential to reduce screening burden, increase screening adherence and provide useful information about home glycemic excursions.

Pancreatic steatosis is common in CF with complete pancreatic fat replacement occurring in some cases. Pancreatic steatosis is also seen in patients with type 2 diabetes and may impact insulin secretion or the rate of beta cell decline. MRI is the most sensitive tool for detecting pancreatic steatosis. Ferrozzi described four patterns of pancreatic fat replacement in CF patients: (1) diffusely hyperintense with variable lobular pattern, (2) homogenous hyperintensity without lobular pattern, (3) hyperintense parenchyma with focal hypointensity, and (4) no structural or signal intensity changes. No studies have directly compared the degree of pancreatic steatosis with OGTT derived measures of insulin secretion or glycemic excursions on CGM.

Hepatic steatosis is also common in CF patients and has an unclear impact on insulin sensitivity. Outside of CF, hepatic steatosis is associated with insulin resistance.

This study has two aims:

Aim 1: Determine how closely the FreeStyle Libre Pro CGM can replicate the results of an in-clinic oral glucose tolerance test.

Aim 2: Explore whether pancreatic and hepatic steatosis correlated with insulin secretion and sensitivity in CF patients.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
34
Inclusion Criteria
  • Cystic fibrosis confirmed by sweat chloride or genetics
  • Pancreatic insufficient or pancreatic sufficient
  • No change in insulin status (either initiating or discontinuing) in the past 3 months
Exclusion Criteria
  • CF liver disease with portal hypertension
  • Systemic glucocorticoid exposure the past 2 weeks (does not include inhaled)
  • Current pulmonary exacerbation treated with antibiotics
  • Baseline or current FEV1 <30% at time of recruitment
  • Transplant recipient
  • Pancreatic sufficient on insulin
  • Started CFTR modulator in the past 3 months

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Cystic Fibrosis, Pancreatic SufficientFrequently Sampled Oral Glucose Tolerance Test and CGMCF patients with exocrine pancreatic sufficiency
Cystic Fibrosis, Pancreatic Insufficient, Treated with InsulinMRI Pancreas and LiverCF patients with exocrine pancreatic insufficiency who are treated with insulin therapy for CFRD
Cystic Fibrosis, Pancreatic Insufficient, No InsulinFrequently Sampled Oral Glucose Tolerance Test and CGMCF patients with exocrine pancreatic insufficiency but not treated with insulin therapy
Cystic Fibrosis, Pancreatic Insufficient, No InsulinMRI Pancreas and LiverCF patients with exocrine pancreatic insufficiency but not treated with insulin therapy
Cystic Fibrosis, Pancreatic SufficientMRI Pancreas and LiverCF patients with exocrine pancreatic sufficiency
Cystic Fibrosis, Pancreatic Insufficient, Treated with InsulinFrequently Sampled Oral Glucose Tolerance Test and CGMCF patients with exocrine pancreatic insufficiency who are treated with insulin therapy for CFRD
Primary Outcome Measures
NameTimeMethod
Glycemic agreement between plasma glucose and CGM0 min-120min

Difference between blood glucose and CGM result will be calculated for each time point (0min, 30min, 60min, 90min, 120min).

Pancreatic Fat and Glycemic measures0min-120min

Correlation between the degree of pancreatic fat replacement (Class 1-4 and fat fraction) and measures of beta cell function on glucose tolerance testing

Secondary Outcome Measures
NameTimeMethod
Pancreatic Fat by Modulator Status0min-120min

Comparison of pancreatic fat (Ferrozzi category and fat fraction) in patients who are and are not receiving a CFTR modulator.

CGM results in CFRD vs. CFND0 min-120min

Comparison of CGM parameters (time and excursions \>140mg/dL and \>200mg/dL between patients with insulin treated CFRD and no insulin treated CFRD

Trial Locations

Locations (1)

University Hospitals Cleveland Medical Center

🇺🇸

Cleveland, Ohio, United States

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