Cystic FibrosisNCT03859531
Gastrointestinal Study at Orkambi Therapy in CF Patients
An observational study of Cystic Fibrosis, run by Karolinska University Hospital at 1 site in Sweden.
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis
- How many people
- 20 participants
- Where
- 1 siteSweden
- Study dates
- 27 Feb 2019to 30 Jun 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: CF patients, F508del homozygote, >12 years of age, eligible and planned for Orkambi therapy in Clinical routine.
Who may be able to join
- CF patients F508del homozygote
- >12 years of age
- eligible for Orkambi therapy.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Sweden1 site, 1 recruiting
- Recruiting
Stockholm CF Center
Stockholm, 14186
Isabelle de Monestrol, MD PhD, +468 58580000, isabelle.demonestrol@ki.se
About this study
Official title: Gastrointestinal Outcome Measures Before and After Orkambi Therapy in Cystic Fibrosis (CF) Patients Carrying the F508del Mutation on Both Alleles
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.
Read the 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.
- Conditions
- Cystic Fibrosis
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| CF patients planned to receive Orkambi | CF patients carrying the F508del mutation on both alleles planned to receive Orkambi therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of fecal calprotectin
Is a marker of intestinal inflammation measured in the stool
Measured: 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.
Measured: 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
Measured: Change from baseline at 6 months after commencing treatment with Orkambi
Secondary outcomes (5)
Change in CRP
Inflammatory marker, unit mg/L.
Measured: Change from baseline at 6 months after commencing treatment with Orkambi
Change in sedimentation rate
Inflammatory marker, unit mm.
Measured: 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.
Measured: Change from baseline, 6 months after commencing treatment with Orkambi
Change in liver function tests
ALT, AST, ALP, gamma-GT. Unit: mikrokat/L
Measured: Change from baseline at 6 months after commencing treatment with Orkambi
Change in bilirubin
Bilirubin. Unit: mikromol/L
Measured: Change from baseline at 6 months after commencing treatment with Orkambi
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2019
- Study start27 Feb 2019
- Primary completion30 Jun 2020 (estimated)
- Study completion30 Jun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Karolinska University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Isabelle de Monestrol, Karolinska University Hospital
- Investigators
- Isabelle de Monestrol, MD PhD, Principal investigator, Stockholm CF Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03859531
- Sponsor's protocol ID
- CF-GI-001
- Status last verified
- Feb 2019
- First submitted
- 26 Feb 2019
- Last updated
- 4 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Because this would expose the patients too much
Publications
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.
PubMed 26250833Wainwright 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.
PubMed 26510034Werlin 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.
PubMed 20512061
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gastrointestinal Outcome Measures Before and After Orkambi Therapy in Cystic Fibrosis (CF) Patients Carrying the F508del Mutation on Both Alleles
- ClinicalTrials.gov ID
- NCT03859531
- Acronym / sponsor ID
- CF-GI-001
- Conditions
- Cystic Fibrosis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Karolinska University HospitalUniversity, hospital or other
- Collaborators
- Hadassah Medical Organization, Vertex Pharmaceuticals Incorporated
- Study start
- 27 Feb 2019 (actual)
- Primary completion
- 30 Jun 2020 (estimated)
- Study completion
- 30 Jun 2020 (estimated)
- First posted
- 1 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CF patients planned to receive Orkambi | – | –CF patients carrying the F508del mutation on both alleles planned to receive Orkambi therapy |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- CF patients, F508del homozygote, >12 years of age, eligible and planned for Orkambi therapy in Clinical routine.
Key inclusion criteria (3 listed)
- CF patients F508del homozygote
- >12 years of age
- eligible for Orkambi therapy.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Concentration of fecal calprotectin
Time frame: 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
Time frame: 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)
Time frame: 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
5 secondary outcomes
Change in CRP
Time frame: Change from baseline at 6 months after commencing treatment with Orkambi
Change in sedimentation rate
Time frame: Change from baseline at 6 months after commencing treatment with Orkambi
Concentration of serum electrophoresis.
Time frame: Change from baseline, 6 months after commencing treatment with Orkambi
Change in liver function tests
Time frame: Change from baseline at 6 months after commencing treatment with Orkambi
Change in bilirubin
Time frame: Change from baseline at 6 months after commencing treatment with Orkambi
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2019.
- Background: PubMed 26250833Borowitz 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.
- Background: PubMed 26510034Wainwright 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.
- Background: PubMed 20512061Werlin 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.
- Individual participant dataSharing planned: No. Because this would expose the patients too much
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Isabelle de Monestrol, MD PhD principal investigator
Stockholm CF Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis, run by Karolinska University Hospital at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of fecal calprotectin (time frame: Change from baseline at 6 months after commencing treatment with Orkambi). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03859531, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2019.