Observational Study of Glucose Tolerance Abnormalities in Patient With Cystic Fibrosis Homozygous for Phe 508 Del CFTR Treated by Lumacaftor-Ivacaftor (GLUCORRECTOR)

Cystic Fibrosis related diabetes (CFRD), a major factor of morbid-mortality in CF, is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years.

At the physiopathology level, insulin secretion is determinant in the glucose tolerance abnormalities in CF. Indeed insulin secretion is dependent of the CFTR activity at the beta cell surface and inhibition of CFTR leads to a decrease in insulin secretion.

Recently, the combination of the lumacaftor, a CFTR corrector, with Ivacaftor, a CFTR potentiator, was studied in patient with CF homozygous for the Phe508 del CFTR mutation patients and showed an improvement of the respiratory state in comparison with the placebo group.

These data suggests that lumacaftor in combination with ivacaftor in targeting CFTR action may have an early impact on the insulin-secretion and consequently on the glucose tolerance.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis Homozygous for Phe 508 Del CFTR; Glucose Intolerance or Newly Diagnosis Diabetes
• Intervention / Treatment: Drug: Lumacaftor-Ivacaftor treatment

• Study Type: Observational
• Enrollment (Actual): 55

Contacts and Locations

Study Locations

• France
  • Angers, France, 49033
    • Centre Hospitalier Universitaire d'Angers
  • Giens, France, 83406
    • Hôpital Renée Sabran
  • Lyon, France, 69000
    • Centre Hospitalier Lyon Sud
  • Marseille, France, 13385
    • Hôpital NORD - Assistance Publique Hôpitaux de Marseille
  • Montpellier, France, 34295
    • Hopital Arnaud de Villeneuve
  • Paris, France, 75019
    • Hopital Robert Debre
  • Reims, France, 51092
    • American Memorial Hospital
  • Roscoff, France, 29684
    • Clinique "Mucoviscidose" Presqu'île de Perharidy
  • Rouen, France, 76031
    • Hopital Charles Nicolle
  • Suresnes, France, 92151
    • Hôpital Foch
  • Tours, France, 37044
    • Hopital Bretonneau - CHRU de Tours
  • Tours, France, 37044
    • Hôpital de Clocheville - CHRU de Tours
  • Alsace
    • Strasbourg, Alsace, France, 67000
      • Hôpitaux Universitaires de Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patient with cystic fibrosis homozygous for Phe 508 del CFTR having a glucose intolerance or newly diagnosis diabetes

Description

Inclusion Criteria:

• patients with CF homozygous for the Phe508del CFTR mutation aged 12 years and over
• Combined Lumacaftor-Ivacaftor treatment scheduled or already started
• glucose intolerance in OGTT (ADA criteria) or newly diabetes diagnosed at the OGTT (ADA criteria) or diabetic patients with insulin requirement ≤ 0.3 unit / kg / day or without insulin treatment
• signed informed consent of patient and of one parent OR legal representative for minor subject

Exclusion Criteria:

• hypersensitivity to the active substances or to any of the excipients of Lumactfor -Ivacaftor
• lung and/or liver transplant patient
• Known diabetes with insulin treatment > 0.3 unit / kg / day
• patient pregnant or wishing to pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patient; Patient with cystic fibrosis homozygous for Phe 508 del CFTR having a glucose intolerance or newly diagnosis diabetes	Drug: Lumacaftor-Ivacaftor treatment; Lumacaftor-Ivacaftor treatment during one year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Measure of 2 hours plasma glucose value (mmol/l) of OGTT, change from baseline at one year of Lumacaftor-Ivacaftor treatment	Day 0 (traitement beginning) and year 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting and one hour glucose value of OGTT (mmol/l)		Day 0 (traitement beginning) and year 1
C peptide and insulin values at T0, 1 , 2 hours of OGTT (µg/l)		Day 0 (traitement beginning) and year 1
Glucose, insulin and C peptide AUC of OGTT (µU/L)		Day 0 (traitement beginning) and year 1
HOMA -R , HOMA-S		Day 0 (traitement beginning) and year 1
Mean glucose value per day and 2 h after meal (mg/dl)		Day 0 (traitement beginning) and year 1
Duration in hypoglycemic area [hypo CGM = 2 consecutive values below 3.3 mmol/l - % of time spent]		Day 0 (traitement beginning) and year 1
Duration in hyperglycemic area [for glucose value higher than 7.7 mmol/l, % time /24h]	Number hypoglycaemic events (below 3.3mmol/L, from midnight to 6 am) Variability glycemic indexes: MAGE (mg/dl), SD (mg/dl)	Day 0 (traitement beginning) and year 1
Number hypoglycaemic events (below 3.3mmol/L, from midnight to 6 am)	Variability glycemic indexes: MAGE (mg/dl), SD (mg/dl)	Day 0 (traitement beginning) and year 1
Variability glycemic indexes: MAGE (mg/dl), SD (mg/dl)		Day 0 (traitement beginning) and year 1
HbA1c (mmol/l and %)		Day 0 (traitement beginning) and year 1
Daily insulin doses (UI/day)		Day 0 (traitement beginning) and year 1
(BMI) body mass index		Day 0 (traitement beginning) and year 1
Weight (Kg) maximum weight never reached		Day 0 (traitement beginning) and year 1
Albumin and Pre albumin (g/l)		Day 0 (traitement beginning) and year 1
FEV1, Vital Capacity (VC) (L and %)		Day 0 (traitement beginning) and year 1
O2 saturation (%)		Day 0 (traitement beginning) and year 1
Number of cures of antibiotics IV and per os /year and interval between 2 cures (week)		Day 0 (traitement beginning) and year 1

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 11, 2016
• Primary Completion (ACTUAL): April 10, 2019
• Study Completion (ACTUAL): April 10, 2019

Study Registration Dates

• First Submitted: January 15, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (ACTUAL): April 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 24, 2021
• Last Update Submitted That Met QC Criteria: November 23, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Cystic fibrosis; Glucose tolerance abnormalities; CFTR corrector and potentiator
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Hyperglycemia; Pancreatic Diseases; Fibrosis; Glucose Intolerance; Congenital Abnormalities; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: 6403

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