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

J

James J. Peters Veterans Affairs Medical Center

Status and phase

Unknown
Phase 1

Conditions

Gastro Esophageal Reflux Disorder

Treatments

Procedure: Esophageal Motility
Procedure: Exhaled Nitric Oxide
Procedure: Pulmonary Function Examination
Procedure: Bernstein's Acid Clearance Test
Drug: Omeprazole
Device: 24 Hour pH Monitor
Procedure: Exhaled Breath Concentrate (EBC)

Study type

Interventional

Funder types

Other U.S. Federal agency

Identifiers

NCT02584751
RAD-16-02

Details and patient eligibility

About

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.

Full 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.

Enrollment

110 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

110 participants in 4 patient groups

Able-Bodied non-GERD
Active Comparator group
Description:
Able-bodied patients who are not diagnosed with GERD during screening will act as controls.
Treatment:
Procedure: Esophageal Motility
Procedure: Exhaled Nitric Oxide
Procedure: Exhaled Breath Concentrate (EBC)
Procedure: Bernstein's Acid Clearance Test
Device: 24 Hour pH Monitor
Procedure: Pulmonary Function Examination
SCI non-GERD
Active Comparator group
Description:
SCI patients who are not diagnosed with GERD during screening will act as controls
Treatment:
Procedure: Esophageal Motility
Procedure: Exhaled Nitric Oxide
Procedure: Exhaled Breath Concentrate (EBC)
Procedure: Bernstein's Acid Clearance Test
Device: 24 Hour pH Monitor
Procedure: Pulmonary Function Examination
SCI GERD
Experimental group
Description:
For those SCI subjects who are identified with GERD, they will undergo a 8week treatment of Omeprazole to reduce GERD
Treatment:
Procedure: Esophageal Motility
Procedure: Exhaled Nitric Oxide
Procedure: Exhaled Breath Concentrate (EBC)
Procedure: Bernstein's Acid Clearance Test
Drug: Omeprazole
Device: 24 Hour pH Monitor
Procedure: Pulmonary Function Examination
Able-bodied GERD
Active Comparator group
Description:
For those AB subjects who are identified with GERD will act as controls. Note they will not receive treatment for GERD in this study. We will notify their primary care physician during the study so that they may receive treatment.
Treatment:
Procedure: Esophageal Motility
Procedure: Exhaled Nitric Oxide
Procedure: Exhaled Breath Concentrate (EBC)
Procedure: Bernstein's Acid Clearance Test
Device: 24 Hour pH Monitor
Procedure: Pulmonary Function Examination

Trial contacts and locations

1

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Central trial contact

Miroslav Radulovic, MD; Tradd Cummings, MS

Data sourced from clinicaltrials.gov

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