Diagnostic Utility of Amyl Nitrite in Patients With Suspected Achalasia Undergoing High Resolution Esophageal Manometry (HREM)

Not Applicable

Withdrawn

• Conditions: Dysphagia; Achalasia
• Interventions: Drug: Amyl Nitrite

• Registration Number: NCT02428959
• Lead Sponsor: Johns Hopkins University

Brief Summary

This research is being done to see if a study drug called amyl nitrite can be helpful with diagnosing different disorders affecting the lower esophageal sphincter in patients with dysphagia (difficulty swallowing foods) undergoing high resolution esophageal manometry (HRM).

Dysphagia may be one of the symptoms of a condition known as idiopathic achalasia. Achalasia is a disorder of the esophagus, the tube that carries food from the mouth to the stomach. This affects the ability of the esophagus to move food toward the stomach. Pseudoachalasia is a secondary form of achalasia, which has very similar symptoms but is caused by different reasons. Because the treatments for achalasia and pseudoachalasia are different, it is important to correctly diagnose each condition. At this time, there is no way to distinguish the two with the current tests used at Johns Hopkins.

Amyl nitrite relaxes vascular smooth muscle and has been studied previously as a potential means to separate achalasia from pseudoachalasia. Amyl nitrite is approved by the Food and Drug Administration (FDA) for the treatment of cardiac angina. It is not approved for use in motility testing and its use in this study is considered investigational. Investigators hope that the results from the proposed study could have significant clinical implications for patient management by helping doctors distinguish between achalasia and pseudoachalasia and allow them to choose appropriate treatment.

Patients with dysphagia (difficulty swallowing foods) undergoing routinely scheduled high resolution esophageal manometry (HRM) may join this study.

Detailed Description

A single center, prospective study at a tertiary-care referral center (JHH). All patients will be provided with informed consent to undergo HRM with provocation as part of routine care to evaluate dysphagia symptoms or evaluation of known achalasia. All procedures will be performed as part of routine care and therefore no procedures will be performed for the purposes of research specifically.

Primary Objective: To determine the diagnostic advantage of the addition of the provocative amyl nitrite test in patients with dysphagia undergoing high resolution esophageal manometry (HRM)

Secondary Objective:

1. Measure change of LES pressure after amyl nitrite inhalation in patients with dysphagia undergoing high resolution esophageal manometry (HRM)

2. To assess the ability of amyl nitrite inhalation to differentiate achalasia from pseudoachalasia

3. To assess the ability of amyl nitrite inhalation to differentiate partial fundoplication-related dysphagia versus that due to recrudescence of achalasia in patients who have undergone a prior myotomy.

4. To assess the ability of amyl nitrite inhalation to differentiate post-fundoplication dysphagia from a newly diagnosed motility disorder in patients who have undergone a fundoplication for gastroesophageal reflux disease.

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2015-04-20
• Study First Submitted QC: 2015-04-23
• Study First Posted: 2015-04-29
• Primary Completion: 2018-12
• Study Completion: 2018-12
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-26
• Last Update Posted: 2019-09-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• age 18-80 years old
• symptoms of dysphagia or a known history of achalasia

Exclusion Criteria

• Patients with comorbidity and contraindications to use of amyl nitrite inhalation: Glaucoma, Recent head trauma or cerebral hemorrhage, Hypotension, Concurrent use of nitrite, Pregnancy, Aortic stenosis, Patients with increased intracranial pressure, Caution in patients with coronary artery disease, Pulmonary hypertension
• Non-English speakers
• Patients <18 years old
• Those who lack capacity to give consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Amyl Nitrite	Amyl Nitrite	Amyl nitrite is the chemical compound with the formula C5H11ONO. It relaxes vascular smooth muscle.The method of administration is via inhalation with onset of action within of 30 seconds and ends 2-3mins. In a study by Dodds et al., amyl nitrite is used as part of radiologic esophagram test in order to distinguish patients with pseudoachalasia from those with idiopathic achalasia since amyl nitrite has transient effect on the lower esophageal sphincter (LES). The study revealed that the LES pressure in achalasia patient decreases substantially in response to amyl nitrite with the measurable increase in LES diameter of 3 mm to an average of 4.6m. In contrast, amyl nitrite does not relax the LES segment in pseudoachalasia and has no change in LES diameter. Thus, the investigators anticipate amyl nitrite inhalation will be beneficial at the LES during HREM.

Primary Outcome Measures

Name	Time	Method
Measure LES pressure after amyl nitrite inhalation in patients with dysphagia undergoing high resolution esophageal manometry (HRM)	3 months

Secondary Outcome Measures

Name	Time	Method
Measure Blood Pressure and Heart Rate at baseline and after administration of amyl nitrite	1 month
Number of Participants with Adverse Events with amyl nitrite inhalation	1 month

Trial Locations

Locations (1)

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States