Comparing Pregabalin and Placebo in Patients With Persistent Globus Sensation (Lyrica)

Universitaire Ziekenhuizen KU Leuven

Status and phase: Enrolling; Phase 4

Conditions: Globus Sensation

Treatments: Drug: Pregabalin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05432843

S52107

Details and patient eligibility

About

To evaluate the relative merits, safety and effectiveness of pregabalin in globus patients compared with placebo.

Full description

Globus, defined as a feeling of a lump in the throat, unexplained by structural lesions, GERD, or histopathology-based esophageal motility disorders, is a frequently occurring symptom of unknown etiology. Today there is no appropriate treatment for patients with a globus sensation. Pathophysiological mechanisms that have been implicated in the pathogenesis of globus include gastroesophageal reflux disease, oesophageal motor disorders, overactive cricopharyngeal muscle, psychological factors, gastric islet patches in the proximal esophagus and deformations of the cervical spine. However, none of these convincingly explains the clinical picture in globus patients.

Investigators recently observed that a large majority (80%) of patients with persistent globus sensation have a pathological EMG examination of the larynx, indicative of neuropathy in the laryngeal area. The investigators believe that this neuropathy may explain some of the symptoms that are experienced by patients with globus, and may actually contribute to some observations of unclear pathophysiological relevance such as a hyperreactive ciricopharyngeal muscle. Neuropathies may respond to specific therapies, such as the pregabalin.

The aim of the study is to evaluate if treatment with pregabalin (Lyrica®) is effective in these patients. The effect of gabapentin, another anti-epileptic drug with therapeutic efficacy in neuropathy, was evaluated in patients with chronic cough as sign of laryngeal sensory neuropathy. In this study 68% of the patients experienced improvement, with an even higher efficacy in the group of patients with a pathological EMG (80%).

In order to better understand the underlying pathophysiology, and how this responds to therapy, the investigators will also evaluate upper esophageal sphincter high resolution manometric properties during the study. An elevated resting pressure in the upper sphincter was already reported in previous studie, but not confirmed in a more recent study, which did report a hyperreactive UES, mainly characterized by a hyperdynamic respiratory pressure change.

Esophageal inlet patches have also been implicated in the pathogenesis of globus, although the exact mechanism remains unclear. In the present study, all patients will undergo a strict evaluation of the upper part of the esophagus during endoscopy, to document presence or absence of inlet patches.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18-80 years
• Globus symptoms for more than three months
• First symptoms > 6 months ago
• Signed informed consent

Exclusion criteria

• Gabapentin/pregabalin treatment
• Unstable neuroleptic or antidepressive treatment (stable dose during min 8 weeks)
• Symptom relief under PPI treatment (min 8 weeks full dose)
• Patients with persisting esophagitis of Los Angeles grade B or higher under PPI on upper GI endoscopy
• Primary esophageal motility disorder (achalasia, scleroderma, dermatomyositis, ...)
• Eosinophilic esophagitis
• Candida esophagitis
• Mechanical explanation of symptoms (e.g. stricture in the pharyngo-esophageal region)
• Pregnancy or plans for pregnancy in the next 12 months (in females)
• History of previous resective gastric or esophageal surgery, cervical spine fusion, Zenker's diverticulum, esophageal epiphrenic diverticulum,

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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90 participants in 2 patient groups, including a placebo group

Pregabalin

Active Comparator group

Description:

Treatment with pregabalin in the treatment of globus sensation

Treatment:

Drug: Pregabalin

Placebo

Placebo Comparator group

Description:

Treatment with placebo in the treatment of globus sensation

Treatment:

Drug: Placebo