Cystic Fibrosis-related Diabetes Clinical Trial
Official title:
Characterization of β-cell Function and Insulin Sensitivity in Pre-transplant Patients With Cystic Fibrosis
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.
Status | Not yet recruiting |
Enrollment | 150 |
Est. completion date | September 1, 2023 |
Est. primary completion date | July 1, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 45 Years |
Eligibility |
Inclusion Criteria: - written informed - diagnosis of cystic fibrosis Exclusion Criteria: - celiac disease - pregnancy - diagnosis of T1DM |
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico |
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* Note: There are 40 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | |
Primary | 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 | |
Primary | TASK 2: prevalence of CFRD in relation to the classes of mutations in the CFTR gene | 2 YEARS | ||
Primary | TASK 3: variation of FEV1 | difference between pre- and post-institution of an optimal glycemic control | 2 YEARS | |
Primary | TASK 4: incidence of post-transplant diabetes in subjects without CFRD | 2 YEARS | ||
Secondary | TASK 2: prevalence of candidate genes for DM2 in the population with CF | 2 YEARS | ||
Secondary | TASK2: variations in the protein pattern expression in CFRD population | highlighted with a proteomic analysis | 2 YEARS | |
Secondary | TASK 3: variations of other respiratory and muscle-performance parameters | n° episodes of exacerbation/year, n° of severe exacerbation (need of hospitalization)/year, and patient-reported outcomes (PROs) obtained from a specific validated questionnaire (CF-quality of life questionnaire, 9 quality of life domains: Physical Functioning, Vitality, Emotional state, Social limitations, Role Limitations/School Performance, Embarrassment, Body Image, Eating Disturbances, Treatment Constraints. 3 symptom scales: Respiratory, Digestive, Weight. 1 health perception scale: Health Status (present/evolution).Scores range from 0 to 100, with higher scores indicating better health) | 2 YEARS |
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