Effect of One Year Elexacaftor-tezacaftor-ivacaftor Treatment (DIATRIM)

DIATRIM : Effect of One Year Elexacaftor-tezacaftor-ivacaftor Treatment on Glucose Tolerance Abnormalities in Adult Patients With Cystic Fibrosis.

The development of CFTR (cystic fibrosis conductance transmembrane regulator) modulators for people with cystic fibrosis (pwCF) and eligible for these treatments is a true therapeutic revolution. The major beneficial effect of CFTR modulators (CFTRm) on pulmonary function and the reduction of pulmonary exacerbations should have a considerable impact on the quality of life and patient's life expectancy. Data on the impact of CFTRm on glucose tolerance abnormalities are still very fragmentary. The investigators can think that their use, earlier and earlier in the history of the disease, will transform the evolutionary trajectories of patients on the respiratory, nutritional and metabolic levels.

Diabetes represents a major challenge in the management of pwCF because it is a factor in morbidity and mortality at all stages of the disease, from children to patients with terminal respiratory failure requiring lung transplantation. Early abnormalities in glucose tolerance observed in childhood, before the stage of diabetes, are also associated with poor pulmonary and nutritional outcomes. Experimental data suggest a positive effect of CFTRm on insulin secretion. However, investigators do not currently know the impact of CFTRm in patients with very early glucose disorders or at the stage of diabetes treated with insulin. Recently continuous glucose measurement (CGM) devices represent very effective tools for assessing abnormalities in glucose tolerance before the stage of diabetes and for monitoring patients treated with insulin.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: elexacaftor-tezacaftor-ivacaftor treatment

• Study Type: Observational
• Enrollment (Actual): 184

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67000
    • Hopitaux universitaires de Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with cystic fibrosis aged over 18, followed in cystic fibrosis ambulatory care services of 18 french centers

Description

Inclusion Criteria:

• Patients with cystic fibrosis aged over 18
• Patients treated for 1 year by elexacaftortezacaftor-ivacaftor
• Normal tolerant or intolerant to glucose or presenting with cystic fibrosis related diabetes treated or not with insulin
• Patient who had a continuous glucose monitoring in the 6 months before and 6 months after one year of treatment with elexacaftor-tezacaftor-ivacaftor

Exclusion Criteria:

• Patient not eligible for triple CFTR modulator
• Patient intolerant to triple corrector
• Pregnant woman

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult patients with cystic fibrosis	Drug: elexacaftor-tezacaftor-ivacaftor treatment; Effect of one year elexacaftor-tezacaftor-ivacaftor treatment on glucose tolerance abnormalities in adult patients with cystic fibrosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate time in range of blood glucose variation >140 mg/dl during 2 weeks in a cohort of adult patients treated for one year with elexacaftor-tezacaftor-ivacaftor	time in range of blood glucose variation >140 mg/dl one year before and one year after the begining of elexacaftor-tezacaftor-ivacaftor treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate other CGM parameters : time in range of blood glucose >180mg/dl ; >140mg/dl ; <70mg/dl ; 70-180 mg/dl ; 70-140mg/dl	One year before and one year after the start of elexacaftor-tezacaftor-ivacaftor treatment
Marker of metabolic status: HbA1c (mmol/l)	One year before and one year after the start of elexacaftor-tezacaftor-ivacaftor treatment
Marker of metabolic status: HbA1c (%)	One year before and one year after the start of elexacaftor-tezacaftor-ivacaftor treatment
Marker of metabolic status: C-Peptid (µg/L)	One year before and one year after the start of elexacaftor-tezacaftor-ivacaftor treatment
Marker of metabolic status: C-Peptid (nmol/L)	One year before and one year after the start of elexacaftor-tezacaftor-ivacaftor treatment
Markers of nutritional status: Evaluation of weight monitoring (kg)	One year before and one year after the start of elexacaftor-tezacaftor-ivacaftor treatment
Markers of nutritional status: Body Mass Index (BMI)	One year before and one year after the start of elexacaftor-tezacaftor-ivacaftor treatment
Diabetes treatment (assess insulin needs) : mean glucose value per day (mg/dl)	One year before and one year after the start of elexacaftor-tezacaftor-ivacaftor treatment
Assessment of respiratory function parameters : number of IV antibiotics	One year before and one year after the start of elexacaftor-tezacaftor-ivacaftor treatment
Number patients with severe hypoglycaemia and serious adverse events	One year before and one year after the start of elexacaftor-tezacaftor-ivacaftor treatment

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2024
• Primary Completion (Actual): February 20, 2025
• Study Completion (Actual): February 24, 2025

Study Registration Dates

• First Submitted: February 23, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2025
• Last Update Submitted That Met QC Criteria: May 5, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Cystic fibrosis; Glucose tolerance abnormalities; Elexacaftor-Tezacaftor-Ivacaftor
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Elexacaftor; Ivacaftor
• Other Study ID Numbers: 9248

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No