Gastrointestinal Study at Orkambi Therapy in CF Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Gastrointestinal Outcome Measures Before and After Orkambi Therapy in Cystic Fibrosis (CF) Patients Carrying the F508del Mutation on Both Alleles

Conditions
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Cystic Fibrosis

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CF patients planned to receive Orkambi<br>CF patients carrying the F508del mutation on both alleles planned to receive Orkambi therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of fecal calprotectin | Is a marker of intestinal inflammation measured in the stool | Change from baseline at 6 months after commencing treatment with Orkambi | 
| Concentration of fecal elastase-1 | Is a test of pancreatic function measured in the stool. | Change from baseline at 6 months after commencing treatment with Orkambi | 
| Change in small bowel capsule endoscopy (SBCE) | 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 | Change from baseline at 6 months after commencing treatment with Orkambi | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CRP | Inflammatory marker, unit mg/L. | Change from baseline at 6 months after commencing treatment with Orkambi | 
| Change in sedimentation rate | Inflammatory marker, unit mm. | Change from baseline at 6 months after commencing treatment with Orkambi | 
| Concentration of serum electrophoresis. | Inflammatory markers: alpha-1-antitrypsin, haptoglobin, orosomucoid, immunoglobulin A, M and G. | Change from baseline, 6 months after commencing treatment with Orkambi | 
| Change in liver function tests | ALT, AST, ALP, gamma-GT. Unit: mikrokat/L | Change from baseline at 6 months after commencing treatment with Orkambi | 
| Change in bilirubin | Bilirubin. Unit: mikromol/L | Change from baseline at 6 months after commencing treatment with Orkambi |