(Study: Vertex IIS) Does Ivacaftor Alter Wild Type CFTR-Open Probability In The Sweat Gland Secretory Coil?
Study Details
Study Description
Brief 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.
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
N/A |
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
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Ivacaftor 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. |
Drug: Ivacaftor
150mg administered orally twice daily.
Other Names:
Drug: β-Adrenergic cocktail
Administered subcutaneously to induce sweating. Cocktail composed of atropine (280µM), isoproterenol (160µM), and aminophylline (20 mM).
Drug: Pilocarpine Nitrate 5%
Administered subcutaneously using Macroduct sweat stimulator device.
Device: Macroduct sweat stimulator
|
Outcome Measures
Primary Outcome Measures
- Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate [Up to 79 days]
CFTR-dependent sweat rate (C-sweat) was analyzed using a linear mixed model, combining on- and off-ivacaftor data.
Secondary Outcome Measures
- Change Sweat Chloride Production [Up to 79 days]
Sweat chloride concentration was measured via the traditional sweat collection methods using the pilocarpine stimulation with the Macroduct device.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy adults without a Cystic Fibrosis (CF) mutation
-
Carriers with a known CF mutation
Exclusion Criteria:
-
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Stanford Hospital and Clinics | Stanford | California | United States | 94305 |
Sponsors and Collaborators
- Richard Barry Moss
Investigators
- Principal Investigator: Jeffrey Wine, PhD, Stanford University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 31238
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Ivacaftor |
---|---|
Arm/Group Description | Participants received ivacaftor orally for 3 days, followed by 35 days off drug. Participants repeated this cycle then received ivacaftor for 3 additional days. For sweat testing, participants received β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant also received pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing was done on- and off-ivacaftor. |
Period Title: Overall Study | |
STARTED | 8 |
COMPLETED | 7 |
NOT COMPLETED | 1 |
Baseline Characteristics
Arm/Group Title | Ivacaftor |
---|---|
Arm/Group Description | Participants received ivacaftor orally for 3 days, followed by 35 days off drug. Participants repeated this cycle then received ivacaftor for 3 additional days. For sweat testing, participants received β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant also received pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing was done on- and off-ivacaftor. |
Overall Participants | 8 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
7
87.5%
|
>=65 years |
1
12.5%
|
Age (years) [Median (Full Range) ] | |
Median (Full Range) [years] |
46.5
|
Sex: Female, Male (Count of Participants) | |
Female |
5
62.5%
|
Male |
3
37.5%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
1
12.5%
|
Not Hispanic or Latino |
7
87.5%
|
Unknown or Not Reported |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
0
0%
|
White |
8
100%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (participants) [Number] | |
United States |
8
100%
|
Healthy Volunteers (Count of Participants) | |
Count of Participants [Participants] |
8
100%
|
Outcome Measures
Title | Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate |
---|---|
Description | CFTR-dependent sweat rate (C-sweat) was analyzed using a linear mixed model, combining on- and off-ivacaftor data. |
Time Frame | Up to 79 days |
Outcome Measure Data
Analysis Population Description |
---|
Participants with available data were included in the analysis. |
Arm/Group Title | Ivacaftor |
---|---|
Arm/Group Description | Participants received ivacaftor orally for 3 days, followed by 35 days off drug. Participants repeated this cycle then received ivacaftor for 3 additional days. For sweat testing, participants received β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant also received pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing was done on- and off-ivacaftor. |
Measure Participants | 7 |
1% β-adrenergic stimulation |
16.45
(2.25)
|
Full β-adrenergic stimulation |
6.60
(2.97)
|
Title | Change Sweat Chloride Production |
---|---|
Description | Sweat chloride concentration was measured via the traditional sweat collection methods using the pilocarpine stimulation with the Macroduct device. |
Time Frame | Up to 79 days |
Outcome Measure Data
Analysis Population Description |
---|
Participants with available data were included in the analysis. |
Arm/Group Title | Ivacaftor |
---|---|
Arm/Group Description | Participants received ivacaftor orally for 3 days, followed by 35 days off drug. Participants repeated this cycle then received ivacaftor for 3 additional days. For sweat testing, participants received β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant also received pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing was done on- and off-ivacaftor. |
Measure Participants | 7 |
On ivacaftor |
25.1
(11.4)
|
Off Ivacaftor |
24.9
(6.1)
|
Adverse Events
Time Frame | Up to 79 days | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Ivacaftor | |
Arm/Group Description | Participants received ivacaftor orally for 3 days, followed by 35 days off drug. Participants repeated this cycle then received ivacaftor for 3 additional days. For sweat testing, participants received β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant also received pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing was done on- and off-ivacaftor. | |
All Cause Mortality |
||
Ivacaftor | ||
Affected / at Risk (%) | # Events | |
Total | 0/8 (0%) | |
Serious Adverse Events |
||
Ivacaftor | ||
Affected / at Risk (%) | # Events | |
Total | 0/8 (0%) | |
Other (Not Including Serious) Adverse Events |
||
Ivacaftor | ||
Affected / at Risk (%) | # Events | |
Total | 1/8 (12.5%) | |
Skin and subcutaneous tissue disorders | ||
Subcutaneous induration | 1/8 (12.5%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Jeff Wine, PhD |
---|---|
Organization | Stanford University |
Phone | 650-725-2462 |
wine@stanford.edu |
- 31238