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NCT Number: NCT02965326

Surrogate Markers of Response to New Therapies in Cystic Fibrosis Patients

The purpose of this study is to determine which biological marker, or association of biological markers, best predict clinical response of cystic fibrosis patients to CFTR modulators.

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

This study is based upon the hypothesis that clinical response of cystic fibrosis patients to CFTR modulators is correlated to in vitro responses to these drugs of epithelial cells derived from the patients, as assessed by CFTR-dependent Chloride secretion. Epithelial cells will be derived either from nasal or rectal epithelia, and consist both of cultured cells and organoids. The drugs tested will be Ivacaftor, or Lumacaftor/Ivacaftor, according to patient's treatment. Results of these assays will be compared with response to treatment at 6 and 12 months, assessed by clinical response and in vivo assay of CFTR function.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Cystic fibrosis patients treated by CFTR modulators (Ivacaftor or the association Ivacaftor-Lumacaftor)
  • Cystic fibrosis patients non treated by CFTR modulators
  • Patients in whom cystic fibrosis diagnosis has been suspected, but excluded by physiological and genetic investigations

Exclusion criteria

  • pregnant or lactating women
  • contraindication to nasal swab
  • contraindication to rectal biopsy

Treatment and study plan

Nasal swab; rectal biopsy.

Procedure

Nasal epithelial cells will be obtained by nasal swabs from patients of the three arms; intestinal epithelial cells will be obtained, by rectal biopsy, only from patients treated by CFTR modulators.

Primary outcomes

  1. Forced Expiratory Volume in 1 second

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months

    Respiratory Function test

Secondary outcomes

  1. Forced Vital Capacity

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months

    Respiratory Function test

  2. Forced Expiratory Flow 25-75

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months

    Respiratory Function test

  3. Residual Volume

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months

    Respiratory Function test

  4. elastase in sputum

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months

    elastase activity in UI/g of sputum

  5. calprotectin in sputum

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months

    calprotectin in µg/g of sputum

  6. IL-8 in sputum

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months

    IL-8 in µg/g of sputum

  7. Calprotectin in blood

    Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months

    calprotectin in µg/ml of blood

  8. IL-8 in blood

    Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months

    IL-8 in µg/ml of blood

  9. tumor necrosis factor in sputum

    Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months

    tumor necrosis factor in µg/g of sputum

  10. liver function test in blood

    Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months

    serum glutamate oxaloacetate transaminase in ui/ml

  11. liver function test/SGPT in blood

    Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months

    serum glutamate pyruvate transaminase in ui/ml

  12. liver function test/bilirubin in blood

    Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months

    Bilirubin in mg/ml

  13. liver function test, gammaGT in blood

    Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months

    GammaGT in UI/ml

  14. creatine phosphokinase in blood

    Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months

    CPK in mg/ml

  15. Amylase in blood

    Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months

    amylase in mg/ml

  16. Impedancemetry

    Time frame: initiation , 1 month, 3 Months, 6 months and every 6 months

    ambulatory measurement of body composition

  17. Dynamometry

    Time frame: initiation , 1 month, 3 Months, 6 months and every 6 months

    ambulatory measurement of quadriceps strength

  18. Sweat test

    Time frame: initiation ,1 month

    chloride concentration in sweat

  19. proteomics of sweat

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months

    measurement of proteins in sweat

  20. metabolomics of sweat

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months

    measurement of métabolites in sweat

  21. proteomics of exhalate

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months

    measurement of proteins in exhaled air

  22. sputum bronchial microorganism colonization

    Time frame: initiation , 1 month, 3 Months, 6 months and every 6 months

    bacterial, fungi and viral colonization

  23. Lung MRI

    Time frame: initiation, at 1 year and every year

    Lung Imaging evaluation : number of bronchiectasis, number of mucus plugs

  24. osteodensitometry

    Time frame: initiation, 1 year, and every year

    Bone mineralization body composition

  25. fecal elastase

    Time frame: initiation, at 6 months and every year

    elastase feces in µg/g feces

  26. fecal calprotectin

    Time frame: initiation, at 6 months and every year

    calprotectin, concentraion in feces in µg/g

  27. Chest CT scan

    Time frame: initiation, 3 years and 5 years

    Lung Imaging: % versuys normal of lung parenchuma with bronchiectasis, airway wall thickening, mucus plugs, air trapping

  28. glycemic Holter

    Time frame: initiation, 1 year and every year

    glycemia monitoring

  29. abdominal ultrasonography

    Time frame: treatment initiation, 1 year and every year

    presence of liver hyperechogenicity, fibrosis, as assessed by the radiologist

  30. proton density fat fraction

    Time frame: treatment initiation, 1 year

    magnetic resonance Imaging of the Pancreas

  31. patient quality of life

    Time frame: initiation, 1 month, 6 months, 1 year and every 6 months

    Score tolerance of the treatment, perception of respiratory, digestive symptoms, energy, body image as assessed by the "Cystic Fibrosis Questionnaire" score a better quality of life is indicated by an increase in the score value. Minimum value is 0, maximum is 100.

  32. CFTR activity in nasal cells/chloride

    Time frame: initiation of treatment and repeated if cell culture failure

    Chloride transport in primary nasal cell cultures obtained by nasal brushing and study in Ussing chamber (µA/cm2)

  33. CFTR activity in nasal cells/bicarbonat

    Time frame: initiation of treatment and repeated if cell culture failure

    Bicarbonate transport in primary nasal cell cultures obtained by nasal brushing and study in Ussing chamber (µA/cm2)

  34. CFTR activity in intestinal epithelium/chloride

    Time frame: initiation of treatment and repeated of cell culture failure

    Chloride transport in intestinal primary culture and study in Ussing chamber (µA/cm2)

  35. CFTR activity in intestinal epithelium/bicarbonate

    Time frame: initiation of treatment and repeated of cell culture failure

    Bicarbonate transport in intestinal primary culture and study in Ussing chamber (µA/cm2)

  36. sweat evaporimetry

    Time frame: initiation and 1 month

    quantity of sweat produced afer bet-adrenergic stimulation after subcutaneous injection

  37. Elasto MRI

    Time frame: initiation and 1 year

    measurement of liver fibrosis by MRI

  38. Lung Clearance Index

    Time frame: initiation, 6 months, 1 year and every 6 months

    Capacity of the lung to washout pure Oxygen,

  39. proteomics in blood

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every year

    measurement of proteins in blood

  40. metabolomics in blood

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every year

    measurement of métabolites in blood

  41. proteomic in urine

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every year

    measurement of proteins in blood

  42. metabolomics in urine

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every year

    measurement of métabolites in urine

  43. Exhaled air composition

    Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every year

    Volatile organic compounds in exhaled air

Study contacts

Contact information is provided by the study sponsor or research team.

Isabelle Sermet, MD, PhD

CONTACT

[email protected]

33 1 44 49 48 87

Jean-Louis Pérignon, MD, PhD

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Hôpital Necker-Enfants Malades

Other

Collaborators

  • Association Mucoviscidose-ABCF2
  • Vaincre la Mucoviscidose

Registry information

Official study title

Personalized Therapy of Cystic Fibrosis: Set-up of Response Markers

Acronym: BIO-CFTR

Important dates

Study start
2016
Primary completion
2026
Study completion
2026
First posted
Nov 16, 2016
Registry last updated
Mar 12, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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