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Pilot of Zinc Acetate to Improve Chronic Cough (ZICO)

Primary Purpose

Cough

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Zinc Acetate 50 Mg Oral Capsule
Placebo oral capsule
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cough focused on measuring Chronic cough, Refractory cough, Chronic refractory cough, Zinc, Zinc acetate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • No upper or lower respiratory infection within 4 weeks

  • Either

    • Negative evaluation for:

      • Asthma; no symptoms of disease or no evidence of asthma based on spirometry and/or methacholine challenge test
      • GERD: no symptoms of acid reflux disease or negative potential of hydrogen (pH) probe
      • Rhinosinusitis/upper airway cough

Or

  • Cough persists despite treatment for the following:

    • Asthma -treated for at least 8 weeks with at least medium dose inhaled corticosteroids or with oral corticosteroids
    • GERD - treated for at least 8 weeks with either a proton pump inhibitor (PPI) or H2 blocker

    • Upper airway disease, postnasal drip or sinusitis - treated for at least 8 weeks with nasal steroids, antihistamines or both.

      • Non-smoker; defined as
  • no smoking of any substance (e.g., tobacco, e-cigarette, marijuana) in the past 6 months, and

  • less than 20 pack-year smoking history

    • Chest x-ray or CT scan in the past 12 months; negative for parenchymal lung diseases (such as interstitial lung disease, idiopathic pulmonary fibrosis, pneumonia, or TB) and negative for lung cancer
    • Overall Cough Visual Analog Scale (Cough-VAS) score of 30 or higher
    • Willing to halt use of zinc supplements or multivitamins containing zinc for the duration of the study
    • Provide written informed consent

Exclusion Criteria:

  • Marijuana use (smoking or ingestion of marijuana) in the past 6 months
  • Use of ACE inhibitor currently or within the past 6 weeks
  • Use of zinc supplements or multivitamins containing zinc currently or within the past 6 weeks
  • Occupational exposure to dust or chemicals that may cause cough, as determined by study physician
  • Diagnosis or evidence of chronic obstructive pulmonary disease (COPD) as defined by forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 0.70 and FEV1% predicted < 80%

  • History of lung disease, such as:

    • Bronchiectasis
    • Interstitial lung disease
    • Sarcoidosis
    • Pneumoconiosis
    • Asbestosis
    • Chronic mycobacterial infection
    • Lung cancer
  • History of pancreatitis
  • Congestive heart failure
  • Chronic kidney disease (creatinine clearance < 30ml/min)
  • Pregnant or breast-feeding
  • Other medical conditions that would interfere with participation in study

Sites / Locations

  • National Jewish Medical and Research Center
  • St. Vincent Health
  • Washington University School of Medicine
  • Mount Sinai School of Medicine
  • Duke University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Zinc Acetate 50 mg oral capsule

Placebo oral capsule

Arm Description

50 mg zinc acetate oral capsules, over-encapsulated, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)

Placebo matched to zinc acetate 50 mg oral capsule active arm, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)

Outcomes

Primary Outcome Measures

Change in Cough Quality of Life Questionnaire (CQLQ) Score by Treatment Group
Unadjusted comparison of change in CQLQ score between zinc acetate and placebo treatment groups. CQLQ scores range from 28 to 112, with lower scores indicating fewer adverse events. A minimum clinically importance difference of 5 has been proposed for this questionnaire.

Secondary Outcome Measures

Change in Leicester Cough Questionnaire (LCQ) Score by Treatment Group
Unadjusted comparison of change in LCQ scores between zinc acetate and placebo treatment groups. LCQ scores range from 3 to 21, with lower scores indicating a greater impact of cough upon one's life. The minimum clinically importance difference for the LCQ for people with chronic cough is 1.3.
Change in Cough Visual Assessment Scale (C-VAS) Scores by Treatment Group
Unadjusted comparison of change in overall severity of cough as measured by C-VAS between zinc acetate and placebo treatment groups. C-VAS scores cover four domains - severity of cough in daytime, nighttime, and overall, and severity of urge to cough. Scores range from 0 to 100 for each domain with overall scores ranging from 0 to 400. Lower scores indicate less severity. Overall severity of cough is the only domain reported here.
Change in Global Assessment of Change in Cough (GACC) Score by Treatment Group
Unadjusted comparison of change in GACC scores between zinc acetate and placebo treatment groups. GACC scores measure change in quality of life related to cough in four domains - activity limitation, symptoms, emotions, and overall quality of life. GACC scores range from -3 (very much worse) to 3 (very much better).

Full Information

First Posted
April 26, 2017
Last Updated
December 28, 2020
Sponsor
Johns Hopkins University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), American Lung Association
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1. Study Identification

Unique Protocol Identification Number
NCT03135522
Brief Title
Pilot of Zinc Acetate to Improve Chronic Cough
Acronym
ZICO
Official Title
Pilot of Zinc Acetate to Improve Chronic Cough
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
February 14, 2018 (Actual)
Primary Completion Date
December 11, 2019 (Actual)
Study Completion Date
December 11, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), American Lung Association

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The Pilot of Zinc Acetate to Improve Chronic Cough (ZICO) is a study of 36 patients with chronic refractory cough that will be used to (1) assess if zinc acetate (150 mg/day) will improve patient reported measures of cough, (2) to establish if treatment with zinc acetate is well tolerated, and (3) to determine if the trial logistics are feasible.
Detailed Description
Chronic refractory cough in adults is defined as a cough lasting more than 8 weeks that does not resolve with treatment for asthma/eosinophilic airway disease, gastroesophageal reflux disease (GERD), or rhinosinusitis/post-nasal drip; and is not caused by smoking, angiotensin-converting-enzyme (ACE) inhibitors, or parenchymal lung disease. This is one of the most common conditions leading to specialty referral accounting for about 20% of new pulmonary consultations. Chronic refractory cough leads to severe impairment of quality of life and social isolation as well as sleep deprivation and chronic fatigue. The few available treatments have limited benefit and substantial side effects or abuse potential. While there are validated tools to measure the health-impact of chronic cough which can provide feasible clinical trial outcome measures, there have been no academic multi-center trials of chronic cough, and guidelines for treatment continue to rely largely on opinion rather than evidence. ZICO is a small scale randomized proof-of-concept clinical trial to establish the safety and tolerability of zinc in this population. The primary outcome measure will be the Cough Specific Quality of Life Questionnaire (CQLQ). Participants will be 18 years or older, with chronic cough lasting at least 3 months, which has been unresponsive to treatments for asthma, GERD or other upper airway disease. Individuals that are current smokers, use an ACE inhibitor, currently take zinc supplements (or multivitamins with zinc), or whose medical history includes primary parenchymal lung disease, congestive heart failure, chronic kidney disease, or another medical condition that could interfere with the study or are pregnant or breast-feeding will be excluded. Participants will be randomized to receive 6 weeks of treatment with either zinc acetate or placebo. Follow-up assessments will occur at 1, 3, 6 and 8 weeks after randomization; the final assessment is after a two week washout to establish the duration of treatment effect. In addition to completing a daily cough diary, participants will complete cough specific and general quality of life measures, complete spirometry testing and have serum zinc and copper levels measured.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cough
Keywords
Chronic cough, Refractory cough, Chronic refractory cough, Zinc, Zinc acetate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zinc Acetate 50 mg oral capsule
Arm Type
Active Comparator
Arm Description
50 mg zinc acetate oral capsules, over-encapsulated, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Arm Title
Placebo oral capsule
Arm Type
Placebo Comparator
Arm Description
Placebo matched to zinc acetate 50 mg oral capsule active arm, administered starting at 1 capsule/day and escalated to 3 capsules/day by Day 8 post-randomization (if tolerated)
Intervention Type
Drug
Intervention Name(s)
Zinc Acetate 50 Mg Oral Capsule
Other Intervention Name(s)
Galzin
Intervention Description
Day 0 (randomization) to day 3 Zinc acetate 50 mg per day (one capsule) Day 4 to day 7 If well tolerated: Zinc acetate 100 mg per day (two capsules) Day 8 to V5 (6 weeks) If well tolerated: Zinc acetate 150 mg per day (three capsules)
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Day 0 (randomization) to day 3 Placebo (one capsule per day) Day 4 to day 7 If well tolerated: placebo (two capsules per day) Day 8 to V5 (6 weeks) If well tolerated: placebo (three capsules per day)
Primary Outcome Measure Information:
Title
Change in Cough Quality of Life Questionnaire (CQLQ) Score by Treatment Group
Description
Unadjusted comparison of change in CQLQ score between zinc acetate and placebo treatment groups. CQLQ scores range from 28 to 112, with lower scores indicating fewer adverse events. A minimum clinically importance difference of 5 has been proposed for this questionnaire.
Time Frame
Baseline and 6 weeks
Secondary Outcome Measure Information:
Title
Change in Leicester Cough Questionnaire (LCQ) Score by Treatment Group
Description
Unadjusted comparison of change in LCQ scores between zinc acetate and placebo treatment groups. LCQ scores range from 3 to 21, with lower scores indicating a greater impact of cough upon one's life. The minimum clinically importance difference for the LCQ for people with chronic cough is 1.3.
Time Frame
Baseline and 6 weeks
Title
Change in Cough Visual Assessment Scale (C-VAS) Scores by Treatment Group
Description
Unadjusted comparison of change in overall severity of cough as measured by C-VAS between zinc acetate and placebo treatment groups. C-VAS scores cover four domains - severity of cough in daytime, nighttime, and overall, and severity of urge to cough. Scores range from 0 to 100 for each domain with overall scores ranging from 0 to 400. Lower scores indicate less severity. Overall severity of cough is the only domain reported here.
Time Frame
Baseline and 6 weeks
Title
Change in Global Assessment of Change in Cough (GACC) Score by Treatment Group
Description
Unadjusted comparison of change in GACC scores between zinc acetate and placebo treatment groups. GACC scores measure change in quality of life related to cough in four domains - activity limitation, symptoms, emotions, and overall quality of life. GACC scores range from -3 (very much worse) to 3 (very much better).
Time Frame
Baseline and 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: No upper or lower respiratory infection within 4 weeks Either Negative evaluation for: Asthma; no symptoms of disease or no evidence of asthma based on spirometry and/or methacholine challenge test GERD: no symptoms of acid reflux disease or negative potential of hydrogen (pH) probe Rhinosinusitis/upper airway cough Or Cough persists despite treatment for the following: Asthma -treated for at least 8 weeks with at least medium dose inhaled corticosteroids or with oral corticosteroids GERD - treated for at least 8 weeks with either a proton pump inhibitor (PPI) or H2 blocker Upper airway disease, postnasal drip or sinusitis - treated for at least 8 weeks with nasal steroids, antihistamines or both. Non-smoker; defined as no smoking of any substance (e.g., tobacco, e-cigarette, marijuana) in the past 6 months, and less than 20 pack-year smoking history Chest x-ray or CT scan in the past 12 months; negative for parenchymal lung diseases (such as interstitial lung disease, idiopathic pulmonary fibrosis, pneumonia, or TB) and negative for lung cancer Overall Cough Visual Analog Scale (Cough-VAS) score of 30 or higher Willing to halt use of zinc supplements or multivitamins containing zinc for the duration of the study Provide written informed consent Exclusion Criteria: Marijuana use (smoking or ingestion of marijuana) in the past 6 months Use of ACE inhibitor currently or within the past 6 weeks Use of zinc supplements or multivitamins containing zinc currently or within the past 6 weeks Occupational exposure to dust or chemicals that may cause cough, as determined by study physician Diagnosis or evidence of chronic obstructive pulmonary disease (COPD) as defined by forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 0.70 and FEV1% predicted < 80% History of lung disease, such as: Bronchiectasis Interstitial lung disease Sarcoidosis Pneumoconiosis Asbestosis Chronic mycobacterial infection Lung cancer History of pancreatitis Congestive heart failure Chronic kidney disease (creatinine clearance < 30ml/min) Pregnant or breast-feeding Other medical conditions that would interfere with participation in study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Wise, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Janet Holbrook, PhD
Organizational Affiliation
Johns Hopkins University Bloomberg School of Public Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Jewish Medical and Research Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
St. Vincent Health
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pilot of Zinc Acetate to Improve Chronic Cough

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