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Gastrointestinal Study at Orkambi Therapy in CF Patients

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ClinicalTrials.gov Identifier: NCT03859531
Recruitment Status : Recruiting
First Posted : March 1, 2019
Last Update Posted : March 4, 2019
Sponsor:
Collaborators:
Hadassah Medical Organization
Vertex Pharmaceuticals Incorporated
Information provided by (Responsible Party):
Isabelle de Monestrol, Karolinska University Hospital

Brief Summary:
Ivacaftor caused a significance increase in weight in patients carrying the G551D mutation and the etiology of this has largely remained unknown but may be due to improved function of the gastrointestinal tract. The combination therapy of Orkambi has been recently approved for subjects with Cystic Fibrosis homozygous for F508del mutation. This provides an opportunity to examine if there are any improvements in gastrointestinal function. The investigators aim to investigate various aspects of gastrointestinal and pancreatic function before and 6 months after the commencement of Orkambi therapy.

Condition or disease
Cystic Fibrosis

Detailed Description:

To examine the entire intestinal mucosa via capsule endoscopy before and 6 months after Orkambi therapy to ascertain if the inflammatory changes in the intestine have improved. A marker of intestinal inflammation measured in the stool, Calprotectin, will be examined before and 6 months after Orkambi treatment. The investigators hypothesize that the result will be reduced on therapy.

A marker of pancreatic exocrine function, pancreatic elastase, will be examined before and 6 months after therapy to examine if the result has increased indicating improvement of exocrine pancreatic function

Study Population All subjects with CF homozygous for the F508del mutation in Sweden eligible for Orkambi therapy, i.e. above 12 years of age, in total 145 patients in Sweden of which 60 are taken care of at Stockholm CF Center; the investigators aim to examine 20 patients.

Study Duration The duration will be 6 months for each patient.

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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Gastrointestinal Outcome Measures Before and After Orkambi Therapy in Cystic Fibrosis (CF) Patients Carrying the F508del Mutation on Both Alleles
Actual Study Start Date : February 27, 2019
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Group/Cohort
CF patients planned to receive Orkambi
CF patients carrying the F508del mutation on both alleles planned to receive Orkambi therapy



Primary Outcome Measures :
  1. Concentration of fecal calprotectin [ Time Frame: Change from baseline at 6 months after commencing treatment with Orkambi ]
    Is a marker of intestinal inflammation measured in the stool

  2. Concentration of fecal elastase-1 [ Time Frame: Change from baseline at 6 months after commencing treatment with Orkambi ]
    Is a test of pancreatic function measured in the stool.

  3. Change in small bowel capsule endoscopy (SBCE) [ Time Frame: Change from baseline at 6 months after commencing treatment with Orkambi ]
    The method of SBCE has been well established as a descriptive diagnostic tool for intestinal inflammation and has been used as an outcome measure in clinical trials. Erythema, petechiae, mucosal erosions and ulcerations will be assessed according to the Maiden criteria


Secondary Outcome Measures :
  1. Change in CRP [ Time Frame: Change from baseline at 6 months after commencing treatment with Orkambi ]
    Inflammatory marker, unit mg/L.

  2. Change in sedimentation rate [ Time Frame: Change from baseline at 6 months after commencing treatment with Orkambi ]
    Inflammatory marker, unit mm.

  3. Concentration of serum electrophoresis. [ Time Frame: Change from baseline, 6 months after commencing treatment with Orkambi ]
    Inflammatory markers: alpha-1-antitrypsin, haptoglobin, orosomucoid, immunoglobulin A, M and G.

  4. Change in liver function tests [ Time Frame: Change from baseline at 6 months after commencing treatment with Orkambi ]
    ALT, AST, ALP, gamma-GT. Unit: mikrokat/L

  5. Change in bilirubin [ Time Frame: Change from baseline at 6 months after commencing treatment with Orkambi ]
    Bilirubin. Unit: mikromol/L



Information from the National Library of Medicine

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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
CF patients, F508del homozygote, >12 years of age, eligible and planned for Orkambi therapy in Clinical routine.
Criteria

Inclusion Criteria:

  • CF patients F508del homozygote
  • >12 years of age
  • eligible for Orkambi therapy.

Exclusion Criteria:

  • Patients who the patency capsule does not pass within 48 hrs
  • FEV1<30%
  • Pregnancy and breastfeeding women
  • Liver function blood tests (AST, ALT, Gamma-GT, ALP) >3 xULN
  • Bilirubin >2 xULN
  • AST or ALT alone >5 xULN
  • Previous lung transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03859531


Locations
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Sweden
Stockholm CF Center Recruiting
Stockholm, Sweden, 14186
Contact: Isabelle de Monestrol, MD PhD    +468 58580000    isabelle.demonestrol@ki.se   
Sponsors and Collaborators
Karolinska University Hospital
Hadassah Medical Organization
Vertex Pharmaceuticals Incorporated
Investigators
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Principal Investigator: Isabelle de Monestrol, MD PhD Stockholm CF Center
  Study Documents (Full-Text)

Documents provided by Isabelle de Monestrol, Karolinska University Hospital:
Study Protocol  [PDF] June 27, 2018

Publications:
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Responsible Party: Isabelle de Monestrol, Director of Stockholm CF Center, Karolinska University Hospital
ClinicalTrials.gov Identifier: NCT03859531    
Other Study ID Numbers: CF-GI-001
First Posted: March 1, 2019    Key Record Dates
Last Update Posted: March 4, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Because this would expose the patients too much

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases