(Study: Vertex IIS) Does Ivacaftor Alter Wild Type CFTR-Open Probability In The Sweat Gland Secretory Coil?

Cystic Fibrosis Clinical Trial

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 Trial Details — Status: Completed

Administrative data

• NCT number: NCT02310789
• Other study ID #: 31238
• Status: Completed
• Phase: N/A
• Start date: July 31, 2015
• Est. completion date: August 23, 2017

Study information

• Verified date: December 2018
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: August 23, 2017
• Est. primary completion date: August 2, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis

Intervention

Drug:
• Ivacaftor
150mg administered orally twice daily.
• ß-Adrenergic cocktail
Administered subcutaneously to induce sweating. Cocktail composed of atropine (280µM), isoproterenol (160µM), and aminophylline (20 mM).
• Pilocarpine Nitrate 5%
Administered subcutaneously using Macroduct sweat stimulator device.

Device:
• Macroduct sweat stimulator

Locations

Country	Name	City	State
United States	Stanford Hospital and Clinics	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Richard Barry Moss

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 79 days
Secondary	Change Sweat Chloride Production	Sweat chloride concentration was measured via the traditional sweat collection methods using the pilocarpine stimulation with the Macroduct device.	Up to 79 days

External Links

•   Sweat rate analysis of ivacaftor potentiation of CFTR in non-CF adults