β-cell Function and Insulin Sensitivity in Patients With Cystic Fibrosis

NCT04379726 | Unknown DMC

• 1 other identifier: FCMilano
• Study Type: observational
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

Cystic fibrosis is a genetic disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, leading to pulmonary infections, sinus disease, pancreatic insufficiency, hepatobiliary disease and male infertility, with respiratory failure being the primary cause of death. Cystic Fibrosis Related Diabetes (CFRD) in one of the most common complication of cystic fibrosis (CF) and it's associated with a worse respiratory and nutritional state, with a negative impact on life expectancy. It differs from type 1 diabetes and type 2 diabetes for particular characteristics making this disease a separated clinical entity. To date, there is a lack of evidence on many aspects concerning this disease:

• the pathophysiology of the disease: decreased insulin secretion has historically been seen has the major trigger for CFRD, but data about this mechanism are scarce and conflicting. Moreover, the role of insulin-resistance seems to be not consistent, but pulmonary exacerbations are very common and, in this setting, insulin sensitivity can worsen significantly.
• the relationship between its development and particular genetic settings: certain CFTR genotypes are known to be most related to the risk of diabetes, and only few susceptibility genes for type 2 diabetes have been evaluated as potential predisposing factors for CFRD.
• the relationship between the therapeutic optimization and its impact on metabolic status and lung function: CFRD is known to be associated with worse clinical outcomes, reflected in more frequent clinical exacerbations, greater reduction in lung function, poorer nutritional status and decreased survival. It has also been demonstrated that insulin therapy can improve pulmonary function, increase body weight and reduce lung exacerbations. However, no study on the clinical impact of the optimization of insulin therapy on pulmonary outcomes and life expectancy are available in this population.
• finally, no data about potential predisposing pre-transplant risk factors for development of post-transplant DM are available For this reason, the investigators have structured a study with the aim to:
• characterize the pathophysiological process leading to CFRD, with assessment of the relative contribution of the insulin resistance and the β-cellular secretion impairment
• define the prevalence of CFRD in relation to the mutations of the CFTR gene and to the presence of candidate genes for the development of type 2 diabetes
• perform a proteomic analysis to identify potential proteomic biomarkers among CFRD patients
• evaluate the body composition, muscle performance and respiratory outcomes in patients on insulin therapy, before and after therapeutic optimization, in a follow-up period of 24 months.
• identify eventual predisposing factors for the development of post-transplant diabetes in subjects without pre-transplant CFRD.

Conditions

Cystic Fibrosis-related Diabetes

Keywords

insulin; beta cell function; insulin resistance

Outcome Measures

Primary Outcomes (6)

• TASK 1: derivative control (DC)

  index of first phase insulin secretion, calculated using the Minimum Model applied to the OGTT in patients with CF and various degrees of glucose homeostasis

  2 YEARS

• TASK 1: proportional control (PC)

  index of second phase insulin secretion, calculated using the Minimum Model applied to the OGTT in patients with CF and various degrees of glucose homeostasis

  2 YEARS

• TASK 1: OGIS-2H

  index of insulin sensitivity, calculated with the appropriate formula applied to the OGTT in patients with CF and various degrees of glucose homeostasis

  2 YEARS

• TASK 2: prevalence of CFRD in relation to the classes of mutations in the CFTR gene

  2 YEARS

• TASK 3: variation of FEV1

  difference between pre- and post-institution of an optimal glycemic control

  2 YEARS

• TASK 4: incidence of post-transplant diabetes in subjects without CFRD

  2 YEARS

Secondary Outcomes (3)

• TASK 2: prevalence of candidate genes for DM2 in the population with CF

  2 YEARS

• TASK2: variations in the protein pattern expression in CFRD population

  2 YEARS

• TASK 3: variations of other respiratory and muscle-performance parameters

  2 YEARS

Study Arms (2)

patients with CFRD

Patients with diagnosis of CFRD, after OGTT

Behavioral: therapeutic optimization

patients without CFRD

Patients without diagnosis of CFRD, after OGTT

Interventions

therapeutic optimization BEHAVIORAL

patients with diagnosis of CFRD will undergo the gold standard treatment for the disease (insulin therapy)

patients with CFRD

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

patients will be followed for three years as described in the protocol

You may qualify if:

• written informed
• diagnosis of cystic fibrosis

You may not qualify if:

• celiac disease
• pregnancy
• diagnosis of T1DM

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead

Related Publications (41)

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Related Links

• Related Info

MeSH Terms

Conditions

Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Emanuela Orsi, MD

CONTACT

0255034590; emanuela.orsi@policlinico.mi.it

Valeria Grancini, MD, PhD

CONTACT

0255033498; valeria.grancini@policlinico.mi.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Diabetology

Study Record Dates

• First Submitted: April 28, 2020
• First Posted: May 7, 2020
• Study Start: July 1, 2020
• Primary Completion: July 1, 2023
• Study Completion: September 1, 2023
• Last Updated: May 7, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share