Clinical trial NCT05099939: Identification of Dysglycemia With Continuous Glucose Monitoring to Assess Clinical Evolution in Cystic Fibrosis
Official title: Identification of Dysglycemia With Continuous Glucose Monitoring: A Prospective Study to Assess the Relationship With Clinical Evolution in Cystic Fibrosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cystic Fibrosis
Keywords: Diabetes
Screening Test
Continuous glucose monitoring
Oral glucose tolerance test
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
Collaborators: name: Centre hospitalier de l'Université de Montréal (CHUM)
name: University Hospital, Strasbourg, France
name: Centre Hospitalier Lyon Sud
name: Fondation Francophone pour la Recherche sur le Diabete
First posted: 2021-10-29
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult individuals living with cystic fibrosis who are being followed at the following centers: Centre Hospitalier de l'Université de Montréal (CHUM), Université de Lyon (Hospices Civils de Lyon) and Université de Strasbourg (CHU de Strasbourg).

Brief summary: Cystic fibrosis (CF)-related diabetes (CFRD) is the most important emerging complication after pulmonary complications. This specific form of diabetes is associated with an increased morbidity and mortality. CFRD prevalence at the age of 10 is 10% and reaches 40 to 50% in adulthood, while a similar percentage is afflicted with milder dysglycemia also called pre-diabetes abnormalities.

In order to identify patients at risk and to implement early therapeutic measures, an annual CFRD screening test is recommended for CF patients after 10 years of age. The standard 2-hour oral glucose tolerance test (OGTT) is the recommended screening test. However, this test is perceived by both patients and CF care teams as unpleasant while adding a significant burden and workload, resulting in screening rates lower than 50% in most centers. An ideal alternative test should be simpler, less invasive, more sensitive than an OGTT to establish risks for lung function and/or nutritional deterioration, and predict future CFRD risk. To date, compared to the OGTT, no alternative screening method has demonstrated its effectiveness. However, continuous glucose monitoring (CGM) is emerging as a possible alternative method.

In patients living with CF, CGM is easy to use and can identify early dysglycemia, which in turn, can predict increased risk of accelerated decline of pulmonary function and/or weight, higher risk of pseudomonas colonization, and future risk of CFRD. However, these observations are based on studies of small sample size with very limited prospective data. Furthermore, many of the multiple CGM metrics that have been standardized are based on the risk of complications associated with Type 1 and Type 2 Diabetes.

Thus, there is a need for prospective studies to identify the CGM metrics and the cut-off level that is relevant as a predictor of clinical deterioration and/or CFRD risk in CF. The identification of such CF-specific criteria would provide important information to target at-risk patients.

Detailed description: The investigators propose an international multicenter observational study to evaluate the predictive value of CGM variables on the evolution of the clinical state in adult patients with CF.

To do this, the following will be evaluated:

* The clinical condition of the patients over a period of 5 years (2 years before, up to 3 years after inclusion);
* The detailed glycemic profile using a CGM system during 3 visits (on inclusion, 1 year, then 2 years after inclusion).

The primary objective is to identify which CGM variable, at inclusion in the study, is the most strongly linked to the risk of a decrease in pulmonary function of more than 2% / year measured by the FEV1% over the 5 years of follow-up of the study. The investigators will also i) investigate which CGM variables are most strongly linked to other clinical markers (ex. nutritional status, CFRD diagnosis and pulmonary exacerbations; ii) assess the association between changes in CGM variables (ex. increased number of glycemic excursions \>11.0 mmol/L over 2 years) and changes in clinical status over time; and iii) evaluate the correlation between plasma glucose values during the standard routine OGTT and CGM values.

This study includes 3 visits with participants: inclusion (V1), the visit at 1 year (V2), then 2 years after inclusion (V3).

This study consists of 3 phases:

* Phase 1: A retrospective file-based data collection, which covers 2 years before inclusion;
* Phase 2: Prospective data collection, including the installation of a CMG 3 times over a period of 2 years, then;
* Phase 3: An additional one-year prospective data collection on file only.

Only phase 2 includes visits for the participant. A CMG system will be installed for 14 days at inclusion (visit 1), at 1 year (visit 2) and 2 years (visit 3) during a regular routine visit and / or an annual OGTT visit. The participants' only involvement will be to wear the CMG system and return it to the research center at the end of the 14-day period. All data obtained during a routine visit will be collected directly from medical records over a period of 5 years (two years before inclusion until the final visit): pulmonary function (FEV1), nutritional status (weight and height), bronchial colonization by Pseudomonas aeruginosa, number of exacerbations, number of intravenous antibiotic courses, number of hospitalizations, and annual OGTT results.

Eligibility criteria: Inclusion Criteria:

* Have cystic fibrosis
* Be 18 years of age or older
* Have given clear and informed consent

Exclusion Criteria:

* Receive pharmaceutical treatment for diabetes
* Have had a lung or liver transplant
* Participate in a randomized controlled trial for more than 3 months in parallel with this study
* Currently pregnant
* Patients under legal protection (for centers in France)

Primary outcomes:
measure: Change in lung function
timeFrame: 5 years
Secondary outcomes:
measure: Change in body mass index
timeFrame: 2 years
measure: Number of pulmonary exacerbations
timeFrame: 1 year
measure: CFRD diagnosis
timeFrame: 3 years
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Institut de recherches cliniques de Montréal
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Strasbourg
country: France
facility: CHU de Strasbourg
Study officials:
affiliation: Institut de recherches cliniques de Montréal
name: Rémi Rabasa-Lhoret
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Strasbourg
name: Laurence Kessler
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospices Civils de Lyon
name: Isabelle Durieu
role: PRINCIPAL_INVESTIGATOR
References: