Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02310789
Recruitment Status : Completed
First Posted : December 8, 2014
Results First Posted : April 20, 2018
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Richard Barry Moss, Stanford University

Tracking Information
First Submitted Date  ICMJE September 3, 2014
First Posted Date  ICMJE December 8, 2014
Results First Submitted Date  ICMJE December 12, 2017
Results First Posted Date  ICMJE April 20, 2018
Last Update Posted Date January 9, 2019
Actual Study Start Date  ICMJE July 31, 2015
Actual Primary Completion Date August 2, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 19, 2018)
Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate [ Time Frame: Up to 79 days ]
CFTR-dependent sweat rate (C-sweat) was analyzed using a linear mixed model, combining on- and off-ivacaftor data.
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2014)
CFTR-dependent sweat rate [ Time Frame: 21-35 days per subject ]
CFTR-dependent sweat rate at two agonist concentrations using cholinergic and beta-adrenergic agonist.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2018)
Change Sweat Chloride Production [ Time Frame: Up to 79 days ]
Sweat chloride concentration was measured via the traditional sweat collection methods using the pilocarpine stimulation with the Macroduct device.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2014)
Sweat chloride concentration [ Time Frame: 21-35 days per subject ]
Sweat chloride concentration
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE (Study: Vertex IIS) Does Ivacaftor Alter Wild Type CFTR-Open Probability In The Sweat Gland Secretory Coil?
Official Title  ICMJE (Study: Vertex IIS) A Study To Access the Effects of Ivacaftor on Wild Type CFTR-Open Probability (PO) In The Sweat Gland Secretory Coil
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • Drug: Ivacaftor
    150mg administered orally twice daily.
    Other Name: Kalydeco
  • Drug: β-Adrenergic cocktail
    Administered subcutaneously to induce sweating. Cocktail composed of atropine (280µM), isoproterenol (160µM), and aminophylline (20 mM).
  • Drug: Pilocarpine Nitrate 5%
    Administered subcutaneously using Macroduct sweat stimulator device.
  • Device: Macroduct sweat stimulator
Study Arms  ICMJE Experimental: 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.
Interventions:
  • Drug: Ivacaftor
  • Drug: β-Adrenergic cocktail
  • Drug: Pilocarpine Nitrate 5%
  • Device: Macroduct sweat stimulator
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 19, 2018)
8
Original Estimated Enrollment  ICMJE
 (submitted: December 5, 2014)
6
Actual Study Completion Date  ICMJE August 23, 2017
Actual Primary Completion Date August 2, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02310789
Other Study ID Numbers  ICMJE 31238
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Richard Barry Moss, Stanford University
Study Sponsor  ICMJE Richard Barry Moss
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeffrey Wine, PhD Stanford University
PRS Account Stanford University
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP