(Study: Vertex IIS) Does Ivacaftor Alter Wild Type CFTR-Open Probability In The Sweat Gland Secretory Coil?
| Status: | Completed |
|---|---|
| Conditions: | Pulmonary |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 1/11/2019 |
| Start Date: | July 31, 2015 |
| End Date: | August 23, 2017 |
(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.
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.
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.
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.
Inclusion Criteria:
- Healthy adults without a Cystic Fibrosis (CF) mutation
- Carriers with a known CF mutation
Exclusion Criteria:
1. Documented liver disease
2. 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.
We found this trial at
1
site
Stanford, California 94305
Principal Investigator: Jeffrey Wine, PhD
Phone: 650-736-0388
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