Clinical trial NCT03859531: Gastrointestinal Study at Orkambi Therapy in CF Patients
Official title: Gastrointestinal Outcome Measures Before and After Orkambi Therapy in Cystic Fibrosis (CF) Patients Carrying the F508del Mutation on Both Alleles
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cystic Fibrosis
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Hadassah Medical Organization
name: Vertex Pharmaceuticals Incorporated
First posted: 2019-03-01
Enrollment: 20
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: CF patients, F508del homozygote, \>12 years of age, eligible and planned for Orkambi therapy in Clinical routine.

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.

Eligibility 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

Primary outcomes:
measure: Concentration of fecal calprotectin
timeFrame: Change from baseline at 6 months after commencing treatment with Orkambi
measure: Concentration of fecal elastase-1
timeFrame: Change from baseline at 6 months after commencing treatment with Orkambi
measure: Change in small bowel capsule endoscopy (SBCE)
timeFrame: Change from baseline at 6 months after commencing treatment with Orkambi
Secondary outcomes:
measure: Change in CRP
timeFrame: Change from baseline at 6 months after commencing treatment with Orkambi
measure: Change in sedimentation rate
timeFrame: Change from baseline at 6 months after commencing treatment with Orkambi
measure: Concentration of serum electrophoresis.
timeFrame: Change from baseline, 6 months after commencing treatment with Orkambi
measure: Change in liver function tests
timeFrame: Change from baseline at 6 months after commencing treatment with Orkambi
measure: Change in bilirubin
timeFrame: Change from baseline at 6 months after commencing treatment with Orkambi
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Stockholm CF Center
Study officials:
affiliation: Stockholm CF Center
name: Isabelle de Monestrol, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Borowitz D, Lubarsky B, Wilschanski M, Munck A, Gelfond D, Bodewes F, Schwarzenberg SJ. Nutritional Status Improved in Cystic Fibrosis Patients with the G551D Mutation After Treatment with Ivacaftor. Dig Dis Sci. 2016 Jan;61(1):198-207. doi: 10.1007/s10620-015-3834-2. Epub 2015 Aug 7.
citation: Wainwright CE, Elborn JS, Ramsey BW. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015 Oct 29;373(18):1783-4. doi: 10.1056/NEJMc1510466. No abstract available.
citation: Werlin SL, Benuri-Silbiger I, Kerem E, Adler SN, Goldin E, Zimmerman J, Malka N, Cohen L, Armoni S, Yatzkan-Israelit Y, Bergwerk A, Aviram M, Bentur L, Mussaffi H, Bjarnasson I, Wilschanski M. Evidence of intestinal inflammation in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):304-8. doi: 10.1097/MPG.0b013e3181d1b013.