Clinical trial NCT03512119: Observational Study of Glucose Tolerance Abnormalities in Patient With Cystic Fibrosis Homozygous for Phe 508 Del CFTR Treated by Lumacaftor-Ivacaftor
Official title: Observational Study of Glucose Tolerance Abnormalities in Patient With Cystic Fibrosis Homozygous for Phe 508 Del CFTR Treated by Lumacaftor-Ivacaftor
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis Homozygous for Phe 508 Del CFTR
Glucose Intolerance or Newly Diagnosis Diabetes
Keywords: Cystic fibrosis
Glucose tolerance abnormalities
CFTR corrector and potentiator
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
First posted: 2018-04-30
Enrollment: 55
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Measure of 2 hours plasma glucose value (mmol/l) of OGTT, change from baseline at one year of Lumacaftor-Ivacaftor treatment
timeFrame: Day 0 (traitement beginning) and year 1
Secondary outcomes:
measure: Fasting and one hour glucose value of OGTT (mmol/l)
timeFrame: Day 0 (traitement beginning) and year 1
measure: C peptide and insulin values at T0, 1 , 2 hours of OGTT (µg/l)
timeFrame: Day 0 (traitement beginning) and year 1
measure: Glucose, insulin and C peptide AUC of OGTT (µU/L)
timeFrame: Day 0 (traitement beginning) and year 1
measure: HOMA -R , HOMA-S
timeFrame: Day 0 (traitement beginning) and year 1
measure: Mean glucose value per day and 2 h after meal (mg/dl)
timeFrame: Day 0 (traitement beginning) and year 1
measure: Duration in hypoglycemic area [hypo CGM = 2 consecutive values below 3.3 mmol/l - % of time spent]
timeFrame: Day 0 (traitement beginning) and year 1
measure: Duration in hyperglycemic area [for glucose value higher than 7.7 mmol/l, % time /24h]
timeFrame: Day 0 (traitement beginning) and year 1
measure: Number hypoglycaemic events (below 3.3mmol/L, from midnight to 6 am)
timeFrame: Day 0 (traitement beginning) and year 1
measure: Variability glycemic indexes: MAGE (mg/dl), SD (mg/dl)
timeFrame: Day 0 (traitement beginning) and year 1
measure: HbA1c (mmol/l and %)
timeFrame: Day 0 (traitement beginning) and year 1
measure: Daily insulin doses (UI/day)
timeFrame: Day 0 (traitement beginning) and year 1
measure: (BMI) body mass index
timeFrame: Day 0 (traitement beginning) and year 1
measure: Weight (Kg) maximum weight never reached
timeFrame: Day 0 (traitement beginning) and year 1
measure: Albumin and Pre albumin (g/l)
timeFrame: Day 0 (traitement beginning) and year 1
measure: FEV1, Vital Capacity (VC) (L and %)
timeFrame: Day 0 (traitement beginning) and year 1
measure: O2 saturation (%)
timeFrame: Day 0 (traitement beginning) and year 1
measure: Number of cures of antibiotics IV and per os /year and interval between 2 cures (week)
timeFrame: Day 0 (traitement beginning) and year 1
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
state: Alsace
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
city: Giens
country: France
facility: Hôpital Renée Sabran
city: Lyon
country: France
facility: Centre Hospitalier Lyon Sud
city: Marseille
country: France
facility: Hôpital NORD - Assistance Publique Hôpitaux de Marseille
city: Montpellier
country: France
facility: Hôpital Arnaud de Villeneuve
city: Paris
country: France
facility: Hôpital Robert Debré
city: Reims
country: France
facility: American Memorial Hospital
city: Roscoff
country: France
facility: Clinique "Mucoviscidose" Presqu'île de Perharidy
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Suresnes
country: France
facility: Hôpital FOCH
city: Tours
country: France
facility: Hôpital Bretonneau - CHRU de Tours
city: Tours
country: France
facility: Hôpital de Clocheville - CHRU de Tours
Study officials:
References: