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

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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

Study Description
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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.


Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Ivacaftor Drug: β-Adrenergic cocktail Drug: Pilocarpine Nitrate 5% Device: Macroduct sweat stimulator Not Applicable

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : July 31, 2015
Actual Primary Completion Date : August 2, 2016
Actual Study Completion Date : August 23, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Ivacaftor

Arms and Interventions
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Arm Intervention/treatment
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.
 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


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02310789


Locations
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United States, California
Stanford Hospital and Clinics
Stanford, California, United States, 94305
Sponsors and Collaborators
Richard Barry Moss
Investigators
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Principal Investigator: Jeffrey Wine, PhD Stanford University
More Information
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Additional Information:

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Responsible Party: Richard Barry Moss, Professor of Pediatrics at the Lucile Salter Packard Children's Hospital, Emeritus, Stanford University
ClinicalTrials.gov Identifier: NCT02310789    
Other Study ID Numbers: 31238
First Posted: December 8, 2014    Key Record Dates
Results First Posted: April 20, 2018
Last Update Posted: January 9, 2019
Last Verified: December 2018
Additional relevant MeSH terms:
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Cystic Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Pilocarpine
Adrenergic Agents
Chloride Channel Agonists
 Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Miotics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents