Gastrointestinal Study at Orkambi Therapy in CF Patients

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03859531
• Other study ID #: CF-GI-001
• Status: Recruiting
• Start date: February 27, 2019
• Est. completion date: June 30, 2020

Study information

• Verified date: February 2019
• Source: Karolinska University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Locations

Country	Name	City	State
Sweden	Stockholm CF Center	Stockholm

Sponsors (3)

Lead Sponsor	Collaborator
Karolinska University Hospital	Hadassah Medical Organization, Vertex Pharmaceuticals Incorporated

Country where clinical trial is conducted

Sweden, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Change in CRP	Inflammatory marker, unit mg/L.	Change from baseline at 6 months after commencing treatment with Orkambi
Secondary	Change in sedimentation rate	Inflammatory marker, unit mm.	Change from baseline at 6 months after commencing treatment with Orkambi
Secondary	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
Secondary	Change in liver function tests	ALT, AST, ALP, gamma-GT. Unit: mikrokat/L	Change from baseline at 6 months after commencing treatment with Orkambi
Secondary	Change in bilirubin	Bilirubin. Unit: mikromol/L	Change from baseline at 6 months after commencing treatment with Orkambi