Uncontrolled Lower Respiratory Symptoms in the WTC Survivor Program

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT02024204
First received: December 18, 2013
Last updated: March 5, 2015
Last verified: March 2015
  Purpose

Our hypothesis is that World Trade Center Environmental Health Center patients with uncontrolled lower respiratory symptoms,that include cough, dyspnea, wheeze and chest tightness, have increased rates of abnormal airway physiology, airway inflammation and co-morbid conditions despite medical therapy. Identifying mechanisms for uncontrolled lower respiratory symptoms (LRS) is imperative to guide therapy with the important potential to reduce secondary adverse health outcomes.

To test this hypothesis, we will conduct a clinical study with aggressive treatment for lower respiratory symptoms in patients in the World Trade Center Environmental Health Center. Patients in the WTC EHC with uncontrolled LRS at visit 1 will be identified and placed on high-dose inhaled corticosteroids and long-acting beta agonists for three months. Adherence will be assessed at monthly visits. Patients will perform spirometry and oscillometry at baseline and after 3 months of treatment. They will also be assessed for markers of airway inflammation, bronchial hyperresponsiveness and co-morbid conditions including depression,anxiety,post-traumatic stress disorder, gastroesophageal reflux, paradoxical vocal cord motion and rhinosinusitis.


Condition Intervention
Lung Diseases
Medication Compliance
Drug: Fluticasone propionate 230mcg/salmeterol 21mcg
Behavioral: Medication Adherence Counseling

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Uncontrolled Lower Respiratory Symptoms in the World Trade Center Survivor Program

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Change in measures of airflow and lung volumes by spirometry and small airway dysfunction by impulse oscillometry and association with uncontrolled lower respiratory symptoms [ Time Frame: Week 1, Week 12 ] [ Designated as safety issue: No ]
    To test whether measurements of airflow and lung volume (spirometry) and of small airway dysfunction (impulse oscillometry) are associated with uncontrolled lower respiratory symptoms

  • Change in lower respiratory symptom control status [ Time Frame: Week 1, Week 12 ] [ Designated as safety issue: No ]
    To test whether a 3-month treatment with combined high-dose inhaled corticosteroids and long-acting bronchodilators results in improved lower respiratory symptoms, assessed by the Asthma Control Test and the Asthma Symptom Utility Index


Secondary Outcome Measures:
  • Bronchial Hyperresponsiveness [ Time Frame: Week 8 ] [ Designated as safety issue: Yes ]
    To test whether bronchial hyperresponsiveness (BHR), assessed by methacholine challenge, is associated with uncontrolled lower respiratory symptoms

  • Inflammatory Markers Associated with Airway Disease (CRP, RAST, Eos and Periostin) [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    To compare levels of circulating biomarkers associated with a Th2 inflammatory response (total and allergen-specific IgE, circulating eosinophils, C-reactive protein, serum periostin) in patients with uncontrolled lower respiratory symptoms and controlled lower respiratory symptoms. The total amount of blood drawn will be 30 mL.

  • Gastroesophageal reflux symptoms [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    To compare rates of gastroesophageal reflux symptoms, assessed by questionnaire, in patients with uncontrolled lower respiratory symptoms and controlled lower respiratory symptoms

  • Chronic rhinosinusitis symptoms [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    To compare rates of chronic rhinosinusitis symptoms, assessed by questionnaire, in patients with uncontrolled lower respiratory symptoms and controlled lower respiratory symptoms

  • Paradoxical vocal cord motion (PVCM) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    To compare rates of paradoxical vocal cord motion, assessed by videolaryngostroboscopy with provocation, in patients with uncontrolled lower respiratory symptoms and controlled lower respiratory symptoms.

  • Changes in levels of fractional exhaled nitric oxide (FeNO) [ Time Frame: Week 1, Week 12 ] [ Designated as safety issue: No ]
    To compare levels of an exhaled marker of inflammation (Fractional exhaled nitric oxide; FeNO) in patients with uncontrolled lower respiratory symptoms and controlled lower respiratory symptoms at baseline and at the end of the 3 month course of treatment.

  • Dyspnea and Functional status [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    To assess dyspnea and functional status using the 6 minute walk test between subjects with uncontrolled and controlled lower respiratory symptoms at the end of the 3 month course of treatment.


Estimated Enrollment: 200
Study Start Date: January 2014
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Visit 1 Uncontrolled LRS
Patients who have uncontrolled LRS (ACT < 20) at time of Visit 1 will be provided with study Advair (Fluticasone propionate 230mcg/salmeterol 21mcg) for a total of 3 months and receive medication adherence counseling Patients who have uncontrolled LRS at V1, but do not fit criteria for Step 3,4 or 5 asthma therapy according to NIH EPR III asthma guidelines will be deferred from the study until they have been seen by their physician and tried on ICS therapy.
Drug: Fluticasone propionate 230mcg/salmeterol 21mcg

Subjects will be further classified at V1 as follows based on ACT:

  • V1 Controlled
  • V1 Uncontrolled

Patients will treated in the following manner based on assessment at V1

  • Patients who have uncontrolled LRS (ACT < 20) at time of this visit will be provided with study Advair for a total of 3 months.
  • Patients who have uncontrolled LRS at V1, but do not fit criteria for Step 3,4 or 5 asthma therapy according to NIH EPR III asthma guidelines will be deferred from the study until they have been seen by their physician and tried on ICS therapy.
  • Patients who had symptoms at monitoring visit but are now controlled at V1 will be asked to continue their current treatment (or no treatment) and will continue with the study. They will not be provided with any medications.
Other Name: Advair HFA
Behavioral: Medication Adherence Counseling
Patients placed on Advair HFA will be instructed in how to use the inhaler and will maintain daily diaries. Inhaler technique will be reviewed in subsequent visits. Notation of the counter denoting actuation of the diskus will be made to assess adherence
No Intervention: Visit 1 Controlled LRS
Patients who had symptoms at monitoring visit but are now controlled at V1 will be asked to continue their current treatment (or no treatment) and will continue with the study. They will not be provided with any medications.

Detailed Description:

Exposure to the dust and fumes of the World Trade Center (WTC) disaster resulted in adverse health including upper and lower respiratory symptoms in responders and community members. The WTC Environmental Health Center (WTC EHC), initiated in 2005, was the first and remains the only treatment program that targets community members, now called "Survivors," including local residents, local workers and clean-up workers with WTC dust and fume exposures. Lower respiratory symptoms are prevalent in patients in the WTC EHC. Most patients with these symptoms in the "Responder" and "Survivor" programs are diagnosed with asthma and this diagnosis has guided therapy. Although spirometry is often normal, diagnosis has been supported by studies showing bronchial hyperresponsiveness (BHR) in some, and distal or small airways disease measured with impulse oscillometry (IOS). As a result, the WTC EHC program has used a treatment algorithm based on guidelines for asthma from the National Institutes of Health. These guidelines focus on the use of "controller" therapy, which includes inhaled corticosteroids (ICS) and long acting bronchodilators (LABA) for persistent symptoms. Despite this approach, eleven years after the destruction of the WTC towers, many patients in the WTC EHC report incomplete clinical response with continued lower respiratory symptoms. In fact, patients with continued uncontrolled lower respiratory symptoms (LRS) remain on treatment with long-term high dose ICS often with additional LABA use, rendering them at risk for adverse health effects of long term ICS treatment. The persistence of symptoms, despite therapeutic interventions, necessitates a reevaluation and a search for causes of persistent symptoms. Possibilities include incomplete adherence with medical regimens, continuing airways disease (BHR or small airways disease) with persistent lung inflammation, or the presence of co-morbid conditions.

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  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years and <75
  • Meet criteria for World Trade Center Environmental Health Center enrollment
  • Onset of lower respiratory symptoms after 9/11/01
  • Persistent lower respiratory symptoms (> 2 times per week)
  • Pre-bronchodilator forced expiratory volume in one second (FEV1) within normal limits
  • < 5 pack-year tobacco history
  • Not current smoker
  • Asthma Control Test Score ≤ 19
  • Normal chest x-ray

Exclusion Criteria:

  • Age < 18 years and ≥75
  • Lower respiratory symptoms or asthma history pre 9/11/01
  • No persistent lower respiratory symptoms
  • pre-bronchodilator FEV1 within normal limits
  • > 5 pack year tobacco
  • Current smoker
  • Abnormal Chest X-Ray or parenchymal changes on high resolution computed tomography
  • Uncontrolled major chronic illness (diabetes mellitus, congestive heart failure, cancer)
  • History of significant non-World Trade Center occupational or environmental exposure
  • Allergy to study drug
  • Pregnancy, lactation or plans to become pregnant
  • Chronic oral corticosteroid use
  • High risk of fatal or near-fatal asthma within the previous 2 years
  • Other lung disease (Idiopathic pulmonary fibrosis,sarcoid, etc.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02024204

Locations
United States, New York
New York University School of Medicine
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Investigators
Principal Investigator: Joan Reibman, M.D NYU School of Medicine
  More Information

Publications:
Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT02024204     History of Changes
Other Study ID Numbers: S13-00448, 1U01OH010404-01A1
Study First Received: December 18, 2013
Last Updated: March 5, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
World Trade Center Disaster
Environmental Exposure
Respiratory Physiology
Inflammation
Gastrointestinal Diseases
Sinus Symptoms
PTSD
Anxiety
Depression
Hypersensitivity
Spirometry
Oscillometry

Additional relevant MeSH terms:
Signs and Symptoms, Respiratory
Signs and Symptoms
Fluticasone
Anti-Allergic Agents
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Dermatologic Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on March 26, 2015