GERD and Anti-Reflux Therapy Between Able-bodied and SCI Individuals

Gastro Esophageal Reflux Disorder Clinical Trial

Official title:

Comparison of GERD and the Effects of Anti-Reflux Therapy on Pulmonary Function Between Able-Bodied and SCI Individuals

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02584751
• Other study ID #: RAD-16-02
• Status: Recruiting
• Phase: Phase 1
• First received: October 9, 2015
• Last updated: November 14, 2016
• Start date: August 2016

Study information

• Verified date: November 2016
• Source: James J. Peters Veterans Affairs Medical Center
• Contact: Miroslav Radulovic, MD
• Phone: 718-584-9000
• Email: miroslav.radulovic[@]va.gov
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Federal Government
• Study type: Interventional

Clinical Trial Summary

Respiratory dysfunction, esophageal dysmotility, and a gastroesophageal reflux disease (GERD) have been demonstrated to be highly prevalent in persons with SCI. GERD has been linked to respiratory symptoms and conditions such as asthma, chronic cough, and an increased rate of respiratory infections in the general population. In persons with asthma, respiratory symptoms and dependency on asthma medications have been reduced by treatment with anti-reflux medication. Possible mechanisms have been proposed for this link, including the microaspiration of reflux materials, which may result in airway acidification and aspiration pneumonia, or the stimulation of the vagus nerve through acid-sensitive receptors in the esophagus with associated esophageal inflammation and reflex bronchoconstriction. Investigators propose to study the effects of anti-reflux therapy (proton pump inhibition) in persons with SCI on objective and subjective symptoms of respiratory function to determine the underlying mechanisms of airway inflammation due to GERD.

Description:

Complete or partial loss of respiratory muscle innervation in individuals with cervical (C1-8) and high thoracic (T1-6) injuries leads to inadequate ventilation and inability to effectively clear secretions, often prompting supportive ventilation following initial injury. Development of atelectasis, pneumonias and respiratory failure are the most common respiratory complications observed during the acute phase of injury. The role of chronic airway inflammation on pulmonary function in persons with SCI is unknown, although the investigators' recent work has shown that individuals with cervical SCI have elevated levels of exhaled nitric oxide (NO), comparable to those seen in mild asthma. It is now widely believed that in the airways of asthmatic patients, the release of NO represents a physiological mechanism to counteract the bronchoconstriction caused by various stimuli. In persons with cervical SCI, bronchoconstriction may represent a consequence of unopposed parasympathetic influence, but alternative mechanisms, such as recurrent infections secondary to impaired cough effectiveness, systemic inflammatory response following SCI, or extra-esophageal manifestations of underlying esophageal dysmotility and/or GERD need to be evaluated. In general population, it has been long recognized that esophageal dysmotility and/or GERD may lead to extra-esophageal manifestations. Reflux can affect both upper and lower respiratory systems leading to the variety of extra-esophageal manifestations, such as reflux asthma, chronic cough, hoarseness, chronic sinusitis, laryngitis, loss of dental enamel, idiopathic pulmonary fibrosis, recurrent pneumonia, chronic bronchitis, etc. 2 possible mechanisms of these complications have been identified: the direct aspiration of reflux content and indirectly, stimulation of vagally-mediated reflexes. Regardless of the underlying mechanisms, treatments with acid-reducing therapies have shown improvement in GERD and extra-esophageal manifestations of the disease the general population. Investigators propose to study the effects of anti-reflux therapy (proton pump inhibition) in persons with SCI on objective and subjective symptoms of respiratory function to determine the underlying mechanisms of airway inflammation due to GERD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. primary completion date: August 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Subjects with Tetraplegia (Level of SCI C4-8);

• Subjects with High Paraplegia (Level of SCI T1-T7);

• Subjects with Low Paraplegia (Level of SCI T8 or below);

• Able-Bodied Subjects (non SCI)

• Duration of injury = 1 year; and

• Chronological age between 18-75 years.

Exclusion Criteria:

• Smoking, active or history of smoking < 6 months;

• Any history of blast injuries to the chest;

• Active respiratory disease or recent (within 3 months) respiratory infections;

• Use of medications known to alter airway caliber (i.e. beta 2 agonists or anticholinergic agents);

• Use of Protein Pump Inhibitors < 8 weeks before testing;

• Use of H2 receptor blockers <8 weeks before testing;

• History of gastrectomy;

• History of esophageal malignancy and/or resection

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastro Esophageal Reflux Disorder
• Gastroesophageal Reflux

Intervention

Drug:
• Omeprazole
Omeprazole is a commonly prescribed anti-reflux medication. If a SCI patient has GERD, they will be prescribed with 40mg omeprazole twice daily for two months

Device:
• 24 Hour pH Monitor
Monitors the acidity and levels of pH in the esophagus for 24hours and helps diagnose people with GERD

Procedure:
• Pulmonary Function Examination
Assess pulmonary function such as lung volumes, spirometry, and max inspiration/expiration pressures.
• Exhaled Nitric Oxide
Used to measure inflammation markers for airway resistance.
• Exhaled Breath Concentrate (EBC)
EBC will be used to measure airway inflammation via specific markers, such as 8-isoprostane. This marker, if elevated, has been identified as an indicator for asthma inflammation.
• Bernstein's Acid Clearance Test
Bernstein test is a clinical test for the diagnosis of chest pain in association with gastric acid exposure
• Esophageal Motility
Esophageal Motility will be used to measure a subject's ability to swallow a bolus (i.e. saline solution) and record pressure changes throughout the esophagus during the swallow. This will also be used to identify anatomical landmarks, such as lower esophageal sphincter, which are necessary for proper placement of 24hr pH catheter.

Locations

Country	Name	City	State
United States	James J. Peters VA Medical Center	Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
James J. Peters Veterans Affairs Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DeMeester Score	A DeMeester score will be calculated from the 24hour pH monitoring to determine if an individual has GERD.	24hours	No
Secondary	Pulmonary Function Tests	Pulmonary Function values and results will be compared to one another to determine if a protein pump inhibitor treatment decreases GERD and improves pulmonary function	2days	No
Secondary	Symptom Surveys and Questionnaires	An 11 question survey assessing GERD and a 15 question survey assessing dysphagia or difficulty swallowing will be used to confirm diagnosis of GERD and compared across the various groups.	2days	No