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

Sponsor

University Hospital, Strasbourg, France (Other)

Overall Status

Completed

CT.gov ID

NCT03512119

Collaborator

(none)

Enrollment

Locations

37.9

Actual Duration (Months)

4.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis Homozygous for Phe 508 Del CFTR Glucose Intolerance or Newly Diagnosis Diabetes	Drug: Lumacaftor-Ivacaftor treatment

Study Design

Study Type:

Observational

Actual Enrollment :

55 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

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

Actual Study Start Date :

Feb 11, 2016

Actual Primary Completion Date :

Apr 10, 2019

Actual Study Completion Date :

Apr 10, 2019

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

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

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] [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)
Number hypoglycaemic events (below 3.3mmol/L, from midnight to 6 am) [Day 0 (traitement beginning) and year 1]
Variability glycemic indexes: MAGE (mg/dl), SD (mg/dl)
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpitaux Universitaires de Strasbourg	Strasbourg	Alsace	France	67000
2	Centre Hospitalier Universitaire d'Angers	Angers		France	49033
3	Hôpital Renée Sabran	Giens		France	83406
4	Centre Hospitalier Lyon Sud	Lyon		France	69000
5	Hôpital NORD - Assistance Publique Hôpitaux de Marseille	Marseille		France	13385
6	Hôpital Arnaud de Villeneuve	Montpellier		France	34295
7	Hôpital Robert Debré	Paris		France	75019
8	American Memorial Hospital	Reims		France	51092
9	Clinique "Mucoviscidose" Presqu'île de Perharidy	Roscoff		France	29684
10	Hôpital Charles Nicolle	Rouen		France	76031
11	Hôpital FOCH	Suresnes		France	92151
12	Hôpital Bretonneau - CHRU de Tours	Tours		France	37044
13	Hôpital de Clocheville - CHRU de Tours	Tours		France	37044