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| Name | Class |
|---|---|
| Hadassah Medical Organization | OTHER |
| Vertex Pharmaceuticals Incorporated | INDUSTRY |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CF patients planned to receive Orkambi | CF patients carrying the F508del mutation on both alleles planned to receive Orkambi therapy |
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| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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CF patients, F508del homozygote, >12 years of age, eligible and planned for Orkambi therapy in Clinical routine.
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| Name | Affiliation | Role |
|---|---|---|
| Isabelle de Monestrol, MD PhD | Stockholm CF Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stockholm CF Center | Recruiting | Stockholm | 14186 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26250833 | Background | 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. | |
| 26510034 | Background |
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Because this would expose the patients too much
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 27, 2018 | Feb 27, 2019 | Prot_000.pdf |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| 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 |
| 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. |
| 20512061 | Background | 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. |
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |