CoughPhase 2ZICONCT03135522
Pilot of Zinc Acetate to Improve Chronic Cough
A Phase 2 study testing Zinc Acetate 50 Mg Oral Capsule in people with Cough, run by Johns Hopkins University at 5 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cough
- What is being tested?
- Zinc Acetate 50 Mg Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 5 sitesUnited States
- Study dates
- 14 Feb 2018to 11 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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
Who cannot join
- 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:
Show all 18Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
National Jewish Medical and Research Center
Denver, Colorado, 80206
Duke University Medical Center
Durham, North Carolina, 27710
St. Vincent Health
Indianapolis, Indiana, 46260
Mount Sinai School of Medicine
New York, New York, 10029
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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.
Read the 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.
- Conditions
- Cough
- Being tested
- Zinc Acetate 50 Mg Oral Capsule, Placebo oral capsule
- Keywords
- Chronic cough, Refractory cough, Chronic refractory cough, Zinc, Zinc acetate
- Medical subject headings
- Cough, Chronic Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zinc Acetate 50 Mg Oral CapsuleDrug
Also called Galzin
- 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)
Placebo oral capsuleDrug
- 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)
| Study group | Role | What they receive |
|---|---|---|
| Zinc Acetate 50 mg oral capsule | Active comparator | 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) Receives: Drug: Zinc Acetate 50 Mg Oral Capsule |
| Placebo oral capsule | Placebo comparator | 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) Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 6 weeks
Secondary outcomes (3)
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.
Measured: Baseline and 6 weeks
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.
Measured: Baseline and 6 weeks
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).
Measured: Baseline and 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2017
- Study start14 Feb 2018
- Primary completion11 Dec 2019
- Study completion11 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CoughStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), American Lung Association
- Responsible party
- Sponsor
- Investigators
- Robert Wise, MD, Principal investigator, Johns Hopkins UniversityJanet Holbrook, PhD, Principal investigator, Johns Hopkins University Bloomberg School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03135522
- Sponsor's protocol ID
- IRB00132534
- Other IDs
- 1R34HL132369-01
- Acronym
- ZICO
- Status last verified
- Dec 2020
- First submitted
- 26 Apr 2017
- Last updated
- 20 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot of Zinc Acetate to Improve Chronic Cough
- ClinicalTrials.gov ID
- NCT03135522
- Acronym / sponsor ID
- ZICO / IRB00132534
- Conditions
- Cough
- Keywords
- Chronic cough, Refractory cough, Chronic refractory cough, Zinc, Zinc acetate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), American Lung Association
- Study start
- 14 Feb 2018 (actual)
- Primary completion
- 11 Dec 2019 (actual)
- Study completion
- 11 Dec 2019 (actual)
- First posted
- 1 May 2017 (actual)
- Results
- Posted 22 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zinc Acetate 50 mg oral capsule | Active comparator | Drug: Zinc Acetate 50 Mg Oral Capsule50 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 oral capsule | Placebo comparator | Drug: Placebo oral capsulePlacebo 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- No upper or lower respiratory infection within 4 weeks
- Either
- Or
- Cough persists despite treatment for the following:
- no smoking of any substance (e.g., tobacco, e-cigarette, marijuana) in the past 6 months, and
Key exclusion criteria (18 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zinc Acetate 50 Mg Oral CapsuleAlso: Galzin* 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) | Drug | Zinc Acetate 50 mg oral capsule |
| Placebo oral capsule* 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) | Drug | Placebo oral capsule |
Primary outcome
Change in Cough Quality of Life Questionnaire (CQLQ) Score by Treatment Group
Time frame: Baseline and 6 weeks
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.
3 secondary outcomes
Change in Leicester Cough Questionnaire (LCQ) Score by Treatment Group
Time frame: Baseline and 6 weeks
Change in Cough Visual Assessment Scale (C-VAS) Scores by Treatment Group
Time frame: Baseline and 6 weeks
Change in Global Assessment of Change in Cough (GACC) Score by Treatment Group
Time frame: Baseline and 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Cough
RecruitingPhase 2
The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC)
Refractory Chronic Cough
RecruitingObservational study
Physical Impairments in Premature Ventricular Complex
Premature Ventricular Complexes
RecruitingObservational study
Office-Based Superior Laryngeal Nerve Block for Treatment of Neurogenic Cough
Cough
Not yet recruiting
High-Flow Nasal Oxygen-Assisted Deep Extubation Versus Awake Extubation in Morbidly Obese Patients
Deep Tracheal Extubation
Recruiting
Feasibility of Cough Skill Training in Individuals With Head and Neck Cancer
Head and Neck Cancers
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Wise, MD principal investigator
Johns Hopkins University
Janet Holbrook, PhD principal investigator
Johns Hopkins University Bloomberg School of Public Health
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zinc Acetate 50 Mg Oral Capsule in people with Cough, run by Johns Hopkins University at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cough Quality of Life Questionnaire (CQLQ) Score by Treatment Group (time frame: Baseline and 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2021.