Clinical trial NCT02310789: (Study: Vertex IIS) Does Ivacaftor Alter Wild Type CFTR-Open Probability In The Sweat Gland Secretory Coil?
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2014-12-08
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate
timeFrame: Up to 79 days
Secondary outcomes:
measure: Change Sweat Chloride Production
timeFrame: Up to 79 days
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
Study officials:
affiliation: Stanford University
name: Jeffrey Wine, PhD
role: PRINCIPAL_INVESTIGATOR
References: