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

NCT02310789 | Completed Results

• 1 other identifier: 31238
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change Sweat Chloride Production

  Up to 79 days

Study Arms (1)

Ivacaftor

EXPERIMENTAL

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; Drug: β-Adrenergic cocktail; Drug: Pilocarpine Nitrate 5%; Device: Macroduct sweat stimulator

Interventions

Ivacaftor DRUG

150mg administered orally twice daily.

Also known as: Kalydeco

Ivacaftor

β-Adrenergic cocktail DRUG

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

Ivacaftor

Pilocarpine Nitrate 5% DRUG

Administered subcutaneously using Macroduct sweat stimulator device.

Ivacaftor

Macroduct sweat stimulator DEVICE

Ivacaftor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adults without a Cystic Fibrosis (CF) mutation
• Carriers with a known CF mutation

You may not qualify if:

• 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.

Sponsors & Collaborators

• Richard Barry Moss: lead

Study Sites (1)

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Related Links

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

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ivacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Jeff Wine, PhD
• Organization: Stanford University

wine@stanford.edu

650-725-2462

Study Officials

• Jeffrey Wine, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics at the Lucile Salter Packard Children's Hospital, Emeritus

Study Record Dates

• First Submitted: September 3, 2014
• First Posted: December 8, 2014
• Study Start: July 31, 2015
• Primary Completion: August 2, 2016
• Study Completion: August 23, 2017
• Last Updated: January 9, 2019
• Results First Posted: April 20, 2018

Record last verified: 2018-12

Locations

US (1)