Cysteamine for Asthma

Study Overview
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Brief Summary
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The purpose of this study is to see if a medicine called Cysteamine, given along with standard asthma care, will improve asthma symptoms and lung function.

Detailed Description
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Asthma affects 25.7 million people in the US. Many people report symptoms despite taking high-doses of inhaled asthma medications. This difficult-to-treat group accounts for more than 50% of asthma related healthcare visits and hospitalizations. The purpose of this study is to see if a medicine called Cysteamine, given along with standard asthma care, will improve asthma symptoms and lung function. This study is a double-blind, placebo-controlled, randomized trial of cysteamine. A placebo arm will be included to determine the comparative effectiveness of cysteamine in this population. Eligible participants will be assessed 1, 4 and 8 weeks post randomization and followed for an additional 4 weeks post treatment. In order to enroll in this study, participants must be between the ages of 18-45 and have uncontrolled asthma. This study will include 4 visits and weekly phone calls, and will be in the study for 3-4 months. During the treatment period, participants will be placed in one of two treatment groups: Cysteamine Placebo Participants will not be able to choose which group they are assigned. This assignment is random and by chance, much like flipping a coin. Participants will not know if they are receiving Cysteamine or placebo. Investigators will compare the study results between the participants of each group.

Official Title
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Cysteamine for Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Cysteamine Bitartrate
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Age ≥ 18 years and ≤ 45 years Provision of written informed consent Asthma currently treated with moderate-high doses of Inhaled Corticosteroids (ICS) per the National Asthma Education and Prevention Program (NAEPP) guidelines by self-report Evidence of hypersensitivity to environmental allergens, with at least one of the following: Elevated serum IgE Positive allergy skin prick testing to at least 1 allergen. Evidence of allergic rhinitis by physical exam or by medical history. Peripheral blood eosinophils ≥150 cells/µl obtained at screening visit. Asthma Severity Score indicating Moderate to Severe Impairment based on EPR-3 classification guidelines > 1 utilization for treatment of asthma exacerbation including prescription of oral or intravenous steroids (urgent care, emergency department visit, or hospitalization for asthma) in the past 12 months Negative urine pregnancy test for females of child bearing potential and use of contraception throughout the study. Exclusion Criteria: Diagnosis of chronic lung disease other than asthma Have received biologic therapy (e.g., anti-IgE, anti-IL-4, anti-IL-5) within 6 months of study entry. Diagnosis of chronic disease other than asthma requiring daily steroids or immunosuppressive agents History of a heart attack or severe chronic heart disease Current smoking or previous history within 1 year Transplant patient IBD, Crohn's History of ulcer, gastric esophageal reflux (GERD) or chronic peptic ulcer disease Pregnant or planning to become pregnant Breastfeeding History of severe allergic or anaphylactic reactions to medications Grade 2-4 Abnormal Laboratory Results (hemoglobin, WBC, lymphocytes, platelets, sodium, potassium, glucose, BUN, creatinine, calcium, albumin, total protein, alkaline phosphate, AST, ALT, and bilirubin), see table 7.4.1.2a and 7.4.1.2b. Grade 3-4 Abnormal Eosinophils and Neutrophils, see table 7.4.1.2a. Evidence of papilledema, or history of pseudotumor cerebri History of persistent headaches Allergic reaction to cysteamine or penicillamine Serious medical condition that, in the opinion of the Study Investigator, would interfere with the ability of the patient to complete the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomized, double-blind, placebo-controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cysteamine<br>Cysteamine Bitartrate plus standard asthma care | Drug: Cysteamine Bitartrate<br>* Cysteamine bitartrate administered four times per day (QID) for 8 weeks. 125mg tablet QID.<br>|
| Placebo Comparator: Placebo Oral Tablet<br>Placebo plus standard asthma care | Drug: Placebo Oral Tablet<br>* Placebo administered for 8 weeks. 125mg tablet QID.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Asthma Symptom Severity Score | Asthma symptom severity score will be classified using the Expert Panel Report 3 (EPR-3) criteria for untreated asthma. The level of impairment is based on the most severe indication of the following criteria: 1. Symptoms, 2. Nighttime awakenings, 3. Short-Acting Beta Agonist (SABA) use for symptom control, 4. Interference with normal activity, and 5. Lung Function. | Baseline (Pre-Treatment), V1 (4 weeks), V2 (8 weeks), Study End (4 weeks post-treatment, Follow-up Phone Call) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days with Albuterol Use Over Time | Albuterol is a bronchodilator used as a rescue medication for treatment of asthma symptoms. | Baseline (Pre-Treatment), V1 (4 weeks), V2 (8 weeks), Study End (4 weeks post-treatment, Follow-up Phone Call) | 
| Change in Inflammation in TH2 cells Over Time | Inflammation as measured by T Helper Type 2 (TH2) cells in peripheral blood. | Baseline (Pre-Treatment), V1 (4 weeks), V2 (8 weeks, End Treatment) | 
| Spirometry Measurement: Forced Expiratory Volume in 1 second (FEV1) Over Time | FEV1 is the amount of air exhaled in 1 second during spirometry. This is used as a measurement of asthma severity. | Baseline (Pre-Treatment), V1 (4 weeks), V2 (8 weeks, End Treatment) | 
| Peak Flow Measurement: Forced Expiratory Volume in 1 second (FEV1) Over Time | FEV1 will be obtained by peak flow measurement. This will be used as a measurement in asthma severity. | Baseline (Pre-Treatment), V1 (4 weeks), V2 (8 weeks), Study End (4 weeks post-treatment, Follow-up Phone Call) | 
| Peak Flow Measurement: Peak Expiratory Flow (PEF) Over Time | PEF will be obtained by peak flow measurement. This will be used as a measurement in asthma severity. | Baseline (Pre-Treatment), V1 (4 weeks), V2 (8 weeks), Study End (4 weeks post-treatment, Follow-up Phone Call) | 
| Change in Asthma Quality of Life Questionnaire (miniAQLQ) scores Over Time | The miniAQLQ will be used to measure the impact that asthma has on participants quality of life. The miniAQLQ will ask questions in the following domains: symptoms, activity limitations, emotional function, and environmental stimuli. There are 15 questions, each with a 7-point scale. An answer of 1 on a question represents the greatest impairment possible and a 7 represents the least impairment. Individual questions are equally weighted. The overall miniAQLQ score is the mean of the responses to each of the 15 questions. | Baseline to Visit 2 (8 weeks) |