World Trade Center Kidney-Link

Obstructive Sleep Apnea Clinical Trial

Official title:

Linking the Effects of 9/11 to Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03234530
• Other study ID #: GCO 16-0899
• Secondary ID: U01OH011326-01A1
• Status: Completed
• Start date: November 1, 2017
• Est. completion date: June 1, 2021

Study information

• Verified date: June 2021
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study focuses on the prevalence and identification of kidney disease among participants of the WTC Health Program and the study team are planning to assess kidney disease in a multi-factorial manner. The first aim of this study is to correlate kidney dysfunction with 9/11 exposure, and the study team predicts that exposure to 9/11 is an independent risk factor in kidney disease among the WTC Health Program participants. Secondly, the study team proposes that a well-established WTC-related condition, obstructive sleep apnea (OSA), is independently associated with kidney disease. In addition, the study team believe there is a temporal causative relationship between evidence of kidney disease and the severity of OSA. Finally, the last aim is to further identify and explore potential mechanisms and phenotypes of kidney disease in participants of the WTC Health Programs.

Regardless of whether the analyses support or reject these hypotheses, the findings will be of equally great public health importance. Successful completion of the proposed research would address a critical knowledge gap regarding the risk of kidney damage among this group of patients, and would inform future mechanistic studies with the potential to impact prevention.

Description:

Exposure to environmental toxins results in significant long-term health effects in workers. More than 91,000 rescue and recovery workers and volunteers at the World Trade Center (WTC) sustained exposure to thousands of tons of coarse and fine particulate matter. Thousands of responders are currently treated for WTC-related health conditions or may be at risk for worsening health. Toxic effects of particulate matter are known to affect the pulmonary, renal and cardiovascular systems. The specific effects of the exposure to 9/11 are partly known, and require further investigation, as outlined in the Zadroga Act (Public Law111-347).

This study builds on the preliminary data to address a critical knowledge gap about the risk of kidney damage among WTC responders, the progression of kidney decline since exposure, and the association of kidney disease with a defined WTC-related diagnosis, obstructive sleep apnea (OSA). Successful completion of the proposed research would address a critical knowledge gap regarding the risk of kidney damage and the relationship to important chronic diseases (OSA and immune-mediated disease) among WTC participants, and would inform future mechanistic studies with the potential to impact disease prevention.

Specific Aim 1: To quantify the risk of kidney damage and the relationship to 9/11 exposure among WTC Health Program participants. Currently, the cohort of 406 first responders represents the sole dedicated evaluation of kidney disease in WTC Health Program participants. The study team will test the hypothesis that exposure to 9/11 is independently associated with kidney disease and enrich the enrollment of the current study population with a diversified population including categories of workers who have not been enrolled, as well as a control group of urban workers (NYC) not exposed to the dust from the WTC.

Aim 1a. The study team hypothesize that albuminuria and decreased estimated glomerular filtration rate (eGFR) will occur more frequently in WTC responders than in the general population and will correlate with the degree of exposure as defined by the previously defined WTC exposure score (adjusting for demographics, family history of chronic kidney disease (CKD), and diagnosed, treated or laboratory confirmed diabetes and hypertension). The study team will also assess established urine biomarkers of proximal tubular injury, including β2-M, Kidney Injury Molecule-1 (KIM-1), and Interleukin 18 (IL-18), as well as markers of distal tubular function, Loop of Henle function, and tubulointerstitial inflammation.

Aim 1b. The study team hypothesize that initial exposure to 9/11 contributed to reduction in renal function over time. The study team will quantify change in renal function over time by analyzing eGFR at WTC Health Program Visit 1 (V1) and subsequent visits, adjusting for known co-morbid conditions.

Aim 1c. The study team will create a repository of WTC responders with established kidney disease (including relatively rare disease) to qualitatively evaluate and describe the spectrum of kidney disease in the entire WTC population and compare to patterns of kidney disease in the general population. The study team will actively enlist those with a verified physician diagnosis of kidney disease, and collect biopsy reports and slides for review.

Specific Aim 2: Evaluate the association of kidney disease and the established WTC-related condition, OSA.

Aim 2a. OSA is particularly prevalent among WTC cohorts. The study team hypothesize that there is an independent association between prevalent OSA and prevalent kidney disease.

Aim2b. The study team hypothesize that OSA independently contributes to the progression of kidney disease. The study team will assess the temporal relationship of eGFR decline to the presence and severity of OSA, using longitudinal data from the WTC data center.

Specific Aim 3: To evaluate potential mechanisms of kidney injury in WTC Health Program participants.

Aim3a. In order to understand the role of chronic inflammation, the study team will evaluate established inflammatory markers which have been implicated as potential mediators of both OSA and CKD, including IL-10, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, IL-12p70., high sensitivity C-reactive protein (hs-CRP), and white blood cell count (WBC).

Aim3b. Based on the preliminary data noting increases in heavy metal levels in urine and blood, the study team will narrow the focus to evaluate the role of cadmium and lead in the development of kidney disease with evaluations of lead content in bone (marker of long-term exposure) as well as in blood. Since study participants include law enforcement personnel (with known exposure to lead), the characterization of bone lead levels will have an important health impact, whether or not a relationship to 9/11 is detected.

Aim3c. In a registry cohort of WTC responders with established kidney disease the study team will explore potential mechanisms as determined by the observed patterns of disease by developing a comprehensive repository of data on WTC Health Program participants with common and rare kidney diseases, the study team will define specific clinical profiles and identify potential mechanisms that warrant future study. Importantly, the study team will develop a process across all WTC Health Programs (inclusive of approximately 50,000 individuals), to monitor those with early kidney disease as well as those with biopsy-proven kidney disease, at any stage.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 555
• Est. completion date: June 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Exposed Group: - Adult patients (35 to 75 years)

• Enrolled or was seen at any of the WTC Clinical Centers of Excellence

Unexposed Group: - Adult patients (35 to 75 years)

• Lived or worked in NYC at least 10 years since 9/11/01 but were not exposed to the the dust at Ground Zero (not living in proximity of Ground Zero, nor involved in the rescue and recovery at Ground Zero

Registry Part: - Adult patient (18 to 75 years)

• Enrolled or was seen at any of the WTC Clinical Centers of Excellence or WTC Environmental Health Centers

• With a diagnosis of any Kidney Injury or disease after 9/11/01

Exclusion Criteria:

• Patients below 18 years of age

• Individuals with an occupation involving chronic exposure to inhaled particulate matter (e.g. iron/steel workers and sand hog workers)

• For the registry part, patients with kidney disease prior to 9/11/01

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Kidney Diseases
• Obstructive Sleep Apnea
• Renal Insufficiency, Chronic
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health (NIOSH/CDC)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	glomerular filtration rate (eGFR)	eGFR will be calculated using the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equations. The proposed studies will evaluate differences in the combined creatinine-cystatin C eGFR, which provides the most accurate estimate of GFR, and the creatinine-based CKD-EPI eGFR, which is more practical for use in clinical practice and in monitoring programs. Values > 200 will be set to 200mL/min/1.73m2	day 1
Primary	albuminuria	albumin level in urine	day 1
Secondary	Berlin questionnaire	Those who are not diagnosed with sleep apnea will be assessed for risk of developing sleep apnea using the Berlin questionnaire. It includes 11 questions organized into three categories, 5 questions related to snoring and the cessation of breathing in category 1, 4 questions related to daytime sleepiness in category 2, 1 question about high blood pressure, and 1 question regarding BMI in category 3. When two of three categories are classified as positive for a patient, the patient is rated as being at high risk of having OSA.	day 1
Secondary	apnea-hypopnea index (AHI)	Those at high risk for sleep apnea will undergo home sleep a study test to determine apnea hypopnea index (AHI).; Those diagnosed with sleep apnea, latest sleep study will be used to obtain AHI. To determine AHI, add the total number of apnea events, plus hypopnea events and divide by the total number of minutes of actual sleep time, then multiply by 60. AHI - Apnea Hypopnea Index - The # of apneas and hypopneas per hour.	day 1