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

• ClinicalTrials.gov Identifier: NCT03512119
• Recruitment Status: Completed
• First Posted: April 30, 2018
• Last Update Posted: April 27, 2020
• Sponsor: University Hospital, Strasbourg, France
• Information provided by (Responsible Party): University Hospital, Strasbourg, France

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
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: February 11, 2016
• Actual Primary Completion Date: April 2018
• Actual Study Completion Date: April 2018

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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

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

Contacts and Locations

Locations

France

Hôpitaux Universitaires de Strasbourg

Strasbourg, Alsace, France, 67000

Centre Hospitalier Universitaire d'Angers

Angers, France, 49033

Hôpital Renée Sabran

Giens, France, 83406

Centre Hospitalier Lyon Sud

Lyon, France, 69000

Hôpital NORD - Assistance Publique Hôpitaux de Marseille

Marseille, France, 13385

Hôpital Arnaud de Villeneuve

Montpellier, France, 34295

Hôpital Robert Debré

Paris, France, 75019

American Memorial Hospital

Reims, France, 51092

Clinique "Mucoviscidose" Presqu'île de Perharidy

Roscoff, France, 29684

Hôpital Charles Nicolle

Rouen, France, 76031

Hôpital FOCH

Suresnes, France, 92151

Hôpital Bretonneau - CHRU de Tours

Tours, France, 37044

Hôpital de Clocheville - CHRU de Tours

Tours, France, 37044

Sponsors and Collaborators

University Hospital, Strasbourg, France

More Information

• Responsible Party: University Hospital, Strasbourg, France
• ClinicalTrials.gov Identifier: NCT03512119
• Other Study ID Numbers: 6403
• First Posted: April 30, 2018
• Last Update Posted: April 27, 2020
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Strasbourg, France:

Cystic fibrosis; Glucose tolerance abnormalities; CFTR corrector and potentiator

Additional relevant MeSH terms:

Cystic Fibrosis; Congenital Abnormalities; Glucose Intolerance; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Ivacaftor; Chloride Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action