Pilot of Zinc Acetate to Improve Chronic Cough

NCT ID: NCT03135522

Last Updated: 2021-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-14
• Study Completion Date: 2019-12-11

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.

Conditions

Cough

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Zinc Acetate 50 mg oral capsule

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)

Group Type: ACTIVE_COMPARATOR

Zinc Acetate 50 Mg Oral Capsule

Intervention Type: DRUG

• 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 capsule

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)

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

• 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)

Interventions

Zinc Acetate 50 Mg Oral Capsule

• 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

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)

Intervention Type: DRUG

Other Intervention Names

Galzin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

American Lung Association

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Wise, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Janet Holbrook, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University Bloomberg School of Public Health

Locations

National Jewish Medical and Research Center

Denver, Colorado, United States

St. Vincent Health

Indianapolis, Indiana, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mount Sinai School of Medicine

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R34HL132369-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00132534

Identifier Type: -

Identifier Source: org_study_id