Glycemic Characterization and Pancreatic Imaging Correlates in Cystic Fibrosis

Cystic Fibrosis Clinical Trial

— CFCGM  

Official title:

Glycemic Characterization and Pancreatic Imaging Correlates in Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03961516
• Other study ID #: 20181150
• Status: Completed
• Start date: May 1, 2019
• Est. completion date: August 30, 2021

Study information

• Verified date: May 2022
• Source: University Hospitals Cleveland Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: August 30, 2021
• Est. primary completion date: August 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Cystic Fibrosis Liver Disease
• Cystic Fibrosis-related Diabetes
• Fatty Liver
• Fibrosis
• Hepatic Steatosis
• Liver Diseases
• Pancreatic Steatosis

Intervention

Device:
• Frequently Sampled Oral Glucose Tolerance Test and CGM
Patients will undergo a 2 hour frequently sampled oral glucose tolerance test while wearing an active FreeStyle Libre Pro sensor. Using as a tool to collect data.

Radiation:
• MRI Pancreas and Liver
Patients will undergo an MRI of the pancreas and liver

Locations

Country	Name	City	State
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
University Hospitals Cleveland Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (15)

Adler AI, Shine BS, Chamnan P, Haworth CS, Bilton D. Genetic determinants and epidemiology of cystic fibrosis-related diabetes: results from a British cohort of children and adults. Diabetes Care. 2008 Sep;31(9):1789-94. doi: 10.2337/dc08-0466. Epub 2008 Jun 5. — View Citation

Annual Data Report 2016 Cystic Fibrosis Foundation Patient Registry [Internet]. Cystic Fibrosis Foundation Patient Registry. 2016

Ayoub F, Trillo-Alvarez C, Morelli G, Lascano J. Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease. World J Hepatol. 2018 Jan 27;10(1):34-40. doi: 10.4254/wjh.v10.i1.34. — View Citation

Della Corte C, Mosca A, Majo F, Lucidi V, Panera N, Giglioni E, Monti L, Stronati L, Alisi A, Nobili V. Nonalcoholic fatty pancreas disease and Nonalcoholic fatty liver disease: more than ectopic fat. Clin Endocrinol (Oxf). 2015 Nov;83(5):656-62. doi: 10.1111/cen.12862. Epub 2015 Aug 12. — View Citation

Engjom T, Kavaliauskiene G, Tjora E, Erchinger F, Wathle G, Lærum BN, Njølstad PR, Frøkjær JB, Gilja OH, Dimcevski G, Haldorsen IS. Sonographic pancreas echogenicity in cystic fibrosis compared to exocrine pancreatic function and pancreas fat content at Dixon-MRI. PLoS One. 2018 Jul 26;13(7):e0201019. doi: 10.1371/journal.pone.0201019. eCollection 2018. — View Citation

Ferrozzi F, Bova D, Campodonico F, De Chiara F, Uccelli M, Bacchini E, Grinzcich R, dè Angelis GL, Battistini A. Cystic fibrosis: MR assessment of pancreatic damage. Radiology. 1996 Mar;198(3):875-9. — View Citation

Franzese A, Valerio G, Buono P, Spagnuolo MI, Sepe A, Mozzillo E, De Simone I, Raia V. Continuous glucose monitoring system in the screening of early glucose derangements in children and adolescents with cystic fibrosis. J Pediatr Endocrinol Metab. 2008 Feb;21(2):109-16. — View Citation

Jefferies C, Solomon M, Perlman K, Sweezey N, Daneman D. Continuous glucose monitoring in adolescents with cystic fibrosis. J Pediatr. 2005 Sep;147(3):396-8. — View Citation

Leclercq A, Gauthier B, Rosner V, Weiss L, Moreau F, Constantinescu AA, Kessler R, Kessler L. Early assessment of glucose abnormalities during continuous glucose monitoring associated with lung function impairment in cystic fibrosis patients. J Cyst Fibros. 2014 Jul;13(4):478-84. doi: 10.1016/j.jcf.2013.11.005. Epub 2013 Dec 17. — View Citation

Li A, Vigers T, Pyle L, Zemanick E, Nadeau K, Sagel SD, Chan CL. Continuous glucose monitoring in youth with cystic fibrosis treated with lumacaftor-ivacaftor. J Cyst Fibros. 2019 Jan;18(1):144-149. doi: 10.1016/j.jcf.2018.07.010. Epub 2018 Aug 10. — View Citation

Lindblad A, Glaumann H, Strandvik B. Natural history of liver disease in cystic fibrosis. Hepatology. 1999 Nov;30(5):1151-8. — View Citation

Mainguy C, Bellon G, Delaup V, Ginoux T, Kassai-Koupai B, Mazur S, Rabilloud M, Remontet L, Reix P. Sensitivity and specificity of different methods for cystic fibrosis-related diabetes screening: is the oral glucose tolerance test still the standard? J Pediatr Endocrinol Metab. 2017 Jan 1;30(1):27-35. doi: 10.1515/jpem-2016-0184. — View Citation

Moran A, Dunitz J, Nathan B, Saeed A, Holme B, Thomas W. Cystic fibrosis-related diabetes: current trends in prevalence, incidence, and mortality. Diabetes Care. 2009 Sep;32(9):1626-31. doi: 10.2337/dc09-0586. Epub 2009 Jun 19. — View Citation

O'Riordan SM, Hindmarsh P, Hill NR, Matthews DR, George S, Greally P, Canny G, Slattery D, Murphy N, Roche E, Costigan C, Hoey H. Validation of continuous glucose monitoring in children and adolescents with cystic fibrosis: a prospective cohort study. Diabetes Care. 2009 Jun;32(6):1020-2. doi: 10.2337/dc08-1925. Epub 2009 Mar 11. — View Citation

Walshaw M. Routine OGTT screening for CFRD - no thanks. J R Soc Med. 2009 Jul;102 Suppl 1:40-4. doi: 10.1258/jrsm.2009.s19009. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemic agreement between plasma glucose and CGM	Difference between blood glucose and CGM result will be calculated for each time point (0min, 30min, 60min, 90min, 120min).	0 min-120min
Primary	Pancreatic Fat and Glycemic measures	Correlation between the degree of pancreatic fat replacement (Class 1-4 and fat fraction) and measures of beta cell function on glucose tolerance testing	0min-120min
Secondary	CGM results in CFRD vs. CFND	Comparison of CGM parameters (time and excursions >140mg/dL and >200mg/dL between patients with insulin treated CFRD and no insulin treated CFRD	0 min-120min
Secondary	Pancreatic Fat by Modulator Status	Comparison of pancreatic fat (Ferrozzi category and fat fraction) in patients who are and are not receiving a CFTR modulator.	0min-120min