Cystic Fibrosis Homozygous for Phe 508 Del CFTR Clinical Trial
— GLUCORRECTOROfficial title:
Observational Study of Glucose Tolerance Abnormalities in Patient With Cystic Fibrosis Homozygous for Phe 508 Del CFTR Treated by Lumacaftor-Ivacaftor
| NCT number | NCT03512119 |
| Other study ID # | 6403 |
| Secondary ID | |
| Status | Completed |
| Phase | |
| First received | |
| Last updated | |
| Start date | February 11, 2016 |
| Est. completion date | April 10, 2019 |
| Verified date | November 2021 |
| Source | University Hospital, Strasbourg, France |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
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.
| Status | Completed |
| Enrollment | 55 |
| Est. completion date | April 10, 2019 |
| Est. primary completion date | April 10, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 12 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| France | Centre Hospitalier Universitaire d'Angers | Angers | |
| France | Hôpital Renée Sabran | Giens | |
| France | Centre Hospitalier Lyon Sud | Lyon | |
| France | Hôpital NORD - Assistance Publique Hôpitaux de Marseille | Marseille | |
| France | Hôpital Arnaud de Villeneuve | Montpellier | |
| France | Hôpital Robert Debré | Paris | |
| France | American Memorial Hospital | Reims | |
| France | Clinique "Mucoviscidose" Presqu'île de Perharidy | Roscoff | |
| France | Hôpital Charles Nicolle | Rouen | |
| France | Hôpitaux Universitaires de Strasbourg | Strasbourg | Alsace |
| France | Hôpital FOCH | Suresnes | |
| France | Hôpital Bretonneau - CHRU de Tours | Tours | |
| France | Hôpital de Clocheville - CHRU de Tours | Tours |
| Lead Sponsor | Collaborator |
|---|---|
| University Hospital, Strasbourg, France |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Fasting and one hour glucose value of OGTT (mmol/l) | Day 0 (traitement beginning) and year 1 | ||
| Secondary | C peptide and insulin values at T0, 1 , 2 hours of OGTT (µg/l) | Day 0 (traitement beginning) and year 1 | ||
| Secondary | Glucose, insulin and C peptide AUC of OGTT (µU/L) | Day 0 (traitement beginning) and year 1 | ||
| Secondary | HOMA -R , HOMA-S | Day 0 (traitement beginning) and year 1 | ||
| Secondary | Mean glucose value per day and 2 h after meal (mg/dl) | Day 0 (traitement beginning) and year 1 | ||
| Secondary | Duration in hypoglycemic area [hypo CGM = 2 consecutive values below 3.3 mmol/l - % of time spent] | Day 0 (traitement beginning) and year 1 | ||
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | Variability glycemic indexes: MAGE (mg/dl), SD (mg/dl) | Day 0 (traitement beginning) and year 1 | ||
| Secondary | HbA1c (mmol/l and %) | Day 0 (traitement beginning) and year 1 | ||
| Secondary | Daily insulin doses (UI/day) | Day 0 (traitement beginning) and year 1 | ||
| Secondary | (BMI) body mass index | Day 0 (traitement beginning) and year 1 | ||
| Secondary | Weight (Kg) maximum weight never reached | Day 0 (traitement beginning) and year 1 | ||
| Secondary | Albumin and Pre albumin (g/l) | Day 0 (traitement beginning) and year 1 | ||
| Secondary | FEV1, Vital Capacity (VC) (L and %) | Day 0 (traitement beginning) and year 1 | ||
| Secondary | O2 saturation (%) | Day 0 (traitement beginning) and year 1 | ||
| Secondary | Number of cures of antibiotics IV and per os /year and interval between 2 cures (week) | Day 0 (traitement beginning) and year 1 |