Cystic Fibrosis
Conditions
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.
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.
Interventions
None listed
Sponsors
Hadassah Medical Organization
Vertex Pharmaceuticals Incorporated
Karolinska University Hospital
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of fecal calprotectin | Change from baseline at 6 months after commencing treatment with Orkambi | Is a marker of intestinal inflammation measured in the stool |
| Concentration of fecal elastase-1 | Change from baseline at 6 months after commencing treatment with Orkambi | Is a test of pancreatic function measured in the stool. |
| Change in small bowel capsule endoscopy (SBCE) | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in liver function tests | Change from baseline at 6 months after commencing treatment with Orkambi | ALT, AST, ALP, gamma-GT. Unit: mikrokat/L |
| Change in CRP | Change from baseline at 6 months after commencing treatment with Orkambi | Inflammatory marker, unit mg/L. |
| Change in bilirubin | Change from baseline at 6 months after commencing treatment with Orkambi | Bilirubin. Unit: mikromol/L |
| Change in sedimentation rate | Change from baseline at 6 months after commencing treatment with Orkambi | Inflammatory marker, unit mm. |
| Concentration of serum electrophoresis. | Change from baseline, 6 months after commencing treatment with Orkambi | Inflammatory markers: alpha-1-antitrypsin, haptoglobin, orosomucoid, immunoglobulin A, M and G. |
Countries
Sweden
Outcome results
None listed