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

NCT ID: NCT02310789

Last Updated: 2019-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2017-08-23

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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ivacaftor

Intervention Type: DRUG

150mg administered orally twice daily.

β-Adrenergic cocktail

Intervention Type: DRUG

Administered subcutaneously to induce sweating. Cocktail composed of atropine (280µM), isoproterenol (160µM), and aminophylline (20 mM).

Pilocarpine Nitrate 5%

Intervention Type: DRUG

Administered subcutaneously using Macroduct sweat stimulator device.

Macroduct sweat stimulator

Intervention Type: DEVICE

Interventions

Ivacaftor

150mg administered orally twice daily.

Intervention Type: DRUG

β-Adrenergic cocktail

Administered subcutaneously to induce sweating. Cocktail composed of atropine (280µM), isoproterenol (160µM), and aminophylline (20 mM).

Intervention Type: DRUG

Pilocarpine Nitrate 5%

Administered subcutaneously using Macroduct sweat stimulator device.

Intervention Type: DRUG

Macroduct sweat stimulator

Intervention Type: DEVICE

Other Intervention Names

Kalydeco

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Richard Barry Moss

OTHER

Sponsor Role: lead

Responsible Party

Richard Barry Moss

Professor of Pediatrics at the Lucile Salter Packard Children's Hospital, Emeritus

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jeffrey Wine, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford Hospital and Clinics

Stanford, California, United States

Countries

United States

Related Links

https://www.nature.com/articles/s41598-018-34308-8

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

Other Identifiers

31238

Identifier Type: -

Identifier Source: org_study_id