Glycemic Characterization and Pancreatic Imaging Correlates in Cystic Fibrosis

NCT ID: NCT03961516

Last Updated: 2022-05-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

34 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-05-01

Study Completion Date

2021-08-30

Brief Summary

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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

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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.

Conditions

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Cystic Fibrosis Cystic Fibrosis-related Diabetes Cystic Fibrosis Liver Disease Pancreatic Steatosis Hepatic Steatosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Cystic Fibrosis, Pancreatic Sufficient

CF patients with exocrine pancreatic sufficiency

Frequently Sampled Oral Glucose Tolerance Test and CGM

Intervention Type DEVICE

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.

MRI Pancreas and Liver

Intervention Type RADIATION

Patients will undergo an MRI of the pancreas and liver

Cystic Fibrosis, Pancreatic Insufficient, No Insulin

CF patients with exocrine pancreatic insufficiency but not treated with insulin therapy

Frequently Sampled Oral Glucose Tolerance Test and CGM

Intervention Type DEVICE

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.

MRI Pancreas and Liver

Intervention Type RADIATION

Patients will undergo an MRI of the pancreas and liver

Cystic Fibrosis, Pancreatic Insufficient, Treated with Insulin

CF patients with exocrine pancreatic insufficiency who are treated with insulin therapy for CFRD

Frequently Sampled Oral Glucose Tolerance Test and CGM

Intervention Type DEVICE

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.

MRI Pancreas and Liver

Intervention Type RADIATION

Patients will undergo an MRI of the pancreas and liver

Interventions

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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.

Intervention Type DEVICE

MRI Pancreas and Liver

Patients will undergo an MRI of the pancreas and liver

Intervention Type RADIATION

Eligibility Criteria

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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
Minimum Eligible Age

6 Years

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospitals Cleveland Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Katherine Kutney

Assistant Professor of Pediatric Endocrinology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Katherine Kutney, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center

Locations

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University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 19542209 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18535191 (View on PubMed)

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

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 27977404 (View on PubMed)

Walshaw M. Routine OGTT screening for CFRD - no thanks. J R Soc Med. 2009 Jul;102 Suppl 1(Suppl 1):40-4. doi: 10.1258/jrsm.2009.s19009. No abstract available.

Reference Type BACKGROUND
PMID: 19605874 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30104123 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24359972 (View on PubMed)

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. doi: 10.1515/jpem.2008.21.2.109.

Reference Type BACKGROUND
PMID: 18422023 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19279304 (View on PubMed)

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. doi: 10.1016/j.jpeds.2005.05.004.

Reference Type BACKGROUND
PMID: 16182684 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26201937 (View on PubMed)

Engjom T, Kavaliauskiene G, Tjora E, Erchinger F, Wathle G, Laerum BN, Njolstad PR, Frokjaer 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.

Reference Type BACKGROUND
PMID: 30048483 (View on PubMed)

Ferrozzi F, Bova D, Campodonico F, De Chiara F, Uccelli M, Bacchini E, Grinzcich R, de Angelis GL, Battistini A. Cystic fibrosis: MR assessment of pancreatic damage. Radiology. 1996 Mar;198(3):875-9. doi: 10.1148/radiology.198.3.8628886.

Reference Type BACKGROUND
PMID: 8628886 (View on PubMed)

Lindblad A, Glaumann H, Strandvik B. Natural history of liver disease in cystic fibrosis. Hepatology. 1999 Nov;30(5):1151-8. doi: 10.1002/hep.510300527.

Reference Type BACKGROUND
PMID: 10534335 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29399276 (View on PubMed)

Other Identifiers

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20181150

Identifier Type: -

Identifier Source: org_study_id

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