Cystic FibrosisNCT02310789
(Study: Vertex IIS) Does Ivacaftor Alter Wild Type CFTR-Open Probability In The Sweat Gland Secretory Coil?
A study testing Ivacaftor, β-Adrenergic cocktail and Pilocarpine Nitrate 5% in people with Cystic Fibrosis, run by Richard Barry Moss at 1 site in United States.
Trial summary
Clinical studies of lumacaftor + ivacaftor (combo therapy) produced better FEV1 (forced expiratory volume in 1 second) improvements than ivacaftor alone, without further improvement in sweat chloride results. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Ivacaftor, β-Adrenergic cocktail and Pilocarpine Nitrate 5%
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jul 2015to 23 Aug 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy adults without a Cystic Fibrosis (CF) mutation
- Carriers with a known CF mutation
Who cannot join
- Documented liver disease
- Participants should not be taking:
- medicines that are strong CYP3A (Cytochrome P450, family 3, subfamily A) inducers, such as:
- the antibiotics rifampin and rifabutin;
- seizure medications (phenobarbital, carbamazepine, or phenytoin); and
- the herbal supplement St. John's Wort, substantially decreases exposure of ivacaftor and may diminish effectiveness.
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford Hospital and Clinics
Stanford, California, 94305
About this study
Official title: (Study: Vertex IIS) A Study To Access the Effects of Ivacaftor on Wild Type CFTR-Open Probability (PO) In The Sweat Gland Secretory Coil
Clinical studies of lumacaftor + ivacaftor (combo therapy) produced better FEV1 (forced expiratory volume in 1 second) improvements than ivacaftor alone, without further improvement in sweat chloride results.
To help understand why sweat chloride was unresponsive, the investigators will use a newly developed sweat secretion test that provides accurate, in vivo readout of CFTR (cystic fibrosis transmembrane conductance regulator) function in the sweat gland secretory coil.
The investigators devised a protocol to determine if short courses of ivacaftor (3.5 days) will produce significant increases in WT (Wild-Type, i.e. normal) CFTR open probability by measuring CFTR-dependent sweating (C-sweat) in subjects with WT CFTR.
Read the detailed description
Cystic fibrosis (CF) is a genetic disease caused by malfunctioning of a protein called CFTR.
CF affects various organs including the sweat glands and the lungs. An FDA approved drug called ivacaftor helps some people with CF, and laboratory tests show that it produces further improvement when combined with an investigational drug called lumacaftor. However, results from clinical tests of the two drugs used together gave mixed results: lung function improved but sweat gland function did not improve. This study will measure CFTR-dependent sweat rate to test the hypothesis that CFTR in the normal sweat glands might be functioning at peak efficiency, and so can't be improved further with ivacaftor, thus accounting for the apparent discrepancy between lung function and sweat gland results. CFTR-dependent sweat rate is important to understanding CF because it is a very accurate measure of CFTR function.
- Conditions
- Cystic Fibrosis
- Being tested
- Ivacaftor, β-Adrenergic cocktail, Pilocarpine Nitrate 5%, Macroduct sweat stimulator
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvacaftorDrug
Also called Kalydeco
150mg administered orally twice daily.
β-Adrenergic cocktailDrug
Administered subcutaneously to induce sweating. Cocktail composed of atropine (280µM), isoproterenol (160µM), and aminophylline (20 mM).
Pilocarpine Nitrate 5%Drug
Administered subcutaneously using Macroduct sweat stimulator device.
Macroduct sweat stimulatorDevice
| Study group | Role | What they receive |
|---|---|---|
| Ivacaftor | Experimental | Participants will receive ivacaftor orally for 3 days, followed by 35 days off drug. Participants will repeat this cycle then receive ivacaftor for 3 additional days. For sweat testing, participants will receive β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant will also receive pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing will be done on- and off-ivacaftor. Receives: Drug: Ivacaftor; Drug: β-Adrenergic cocktail; Drug: Pilocarpine Nitrate 5%; Device: Macroduct sweat stimulator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate
CFTR-dependent sweat rate (C-sweat) was analyzed using a linear mixed model, combining on- and off-ivacaftor data.
Measured: Up to 79 days
Secondary outcomes (1)
Change Sweat Chloride Production
Sweat chloride concentration was measured via the traditional sweat collection methods using the pilocarpine stimulation with the Macroduct device.
Measured: Up to 79 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2014 (estimated)
- Study start31 Jul 2015
- Primary completion2 Aug 2016
- Study completion23 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Richard Barry Moss
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Richard Barry Moss, Stanford University
- Investigators
- Jeffrey Wine, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02310789
- Sponsor's protocol ID
- 31238
- Status last verified
- Dec 2018
- First submitted
- 3 Sep 2014
- Last updated
- 9 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- (Study: Vertex IIS) A Study To Access the Effects of Ivacaftor on Wild Type CFTR-Open Probability (PO) In The Sweat Gland Secretory Coil
- ClinicalTrials.gov ID
- NCT02310789
- Acronym / sponsor ID
- 31238
- Conditions
- Cystic Fibrosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Richard Barry MossUniversity, hospital or other
- Study start
- 31 Jul 2015 (actual)
- Primary completion
- 2 Aug 2016 (actual)
- Study completion
- 23 Aug 2017 (actual)
- First posted
- 8 Dec 2014 (estimated)
- Results
- Posted 20 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clinical studies of lumacaftor + ivacaftor (combo therapy) produced better FEV1 (forced expiratory volume in 1 second) improvements than ivacaftor alone, without further improvement in sweat chloride results.
To help understand why sweat chloride was unresponsive, the investigators will use a newly developed sweat secretion test that provides accurate, in vivo readout of CFTR (cystic fibrosis transmembrane conductance regulator) function in the sweat gland secretory coil.
The investigators devised a protocol to determine if short courses of ivacaftor (3.5 days) will produce significant increases in WT (Wild-Type, i.e. normal) CFTR open probability by measuring CFTR-dependent sweating (C-sweat) in subjects with WT CFTR.
Detailed description
Cystic fibrosis (CF) is a genetic disease caused by malfunctioning of a protein called CFTR.
CF affects various organs including the sweat glands and the lungs. An FDA approved drug called ivacaftor helps some people with CF, and laboratory tests show that it produces further improvement when combined with an investigational drug called lumacaftor. However, results from clinical tests of the two drugs used together gave mixed results: lung function improved but sweat gland function did not improve. This study will measure CFTR-dependent sweat rate to test the hypothesis that CFTR in the normal sweat glands might be functioning at peak efficiency, and so can't be improved further with ivacaftor, thus accounting for the apparent discrepancy between lung function and sweat gland results. CFTR-dependent sweat rate is important to understanding CF because it is a very accurate measure of CFTR function.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ivacaftor | Experimental | Drug: Ivacaftor, Drug: β-Adrenergic cocktail, Drug: Pilocarpine Nitrate 5%, Device: Macroduct sweat stimulatorParticipants will receive ivacaftor orally for 3 days, followed by 35 days off drug. Participants will repeat this cycle then receive ivacaftor for 3 additional days. For sweat testing, participants will receive β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant will also receive pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing will be done on- and off-ivacaftor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy adults without a Cystic Fibrosis (CF) mutation
- Carriers with a known CF mutation
Key exclusion criteria (6 listed)
- Documented liver disease
- Participants should not be taking:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IvacaftorAlso: Kalydeco150mg administered orally twice daily. | Drug | Ivacaftor |
| β-Adrenergic cocktailAdministered subcutaneously to induce sweating. Cocktail composed of atropine (280µM), isoproterenol (160µM), and aminophylline (20 mM). | Drug | Ivacaftor |
| Pilocarpine Nitrate 5%Administered subcutaneously using Macroduct sweat stimulator device. | Drug | Ivacaftor |
| Macroduct sweat stimulator | Device | Ivacaftor |
Primary outcome
Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate
Time frame: Up to 79 days
CFTR-dependent sweat rate (C-sweat) was analyzed using a linear mixed model, combining on- and off-ivacaftor data.
1 secondary outcome
Change Sweat Chloride Production
Time frame: Up to 79 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Sweat rate analysis of ivacaftor potentiation of CFTR in non-CF adultsLink provided by the sponsor.
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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.
Jeffrey Wine, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ivacaftor, β-Adrenergic cocktail and Pilocarpine Nitrate 5% in people with Cystic Fibrosis, run by Richard Barry Moss at 1 site in United States.
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 2 inclusion and 6 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: finished, as of the sponsor's last update on 9 Jan 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 United States. 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?
Yes. Results are posted in the registry (first posted 20 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate (time frame: Up to 79 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jan 2019.