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Comparing Pregabalin and Placebo in Patients With Persistent Globus Sensation

Phase 4
Conditions
Globus Sensation
Interventions
Drug: Placebo
Registration Number
NCT05432843
Lead Sponsor
Universitaire Ziekenhuizen KU Leuven
Brief Summary

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

Detailed 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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
90
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,

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PregabalinPregabalinTreatment with pregabalin in the treatment of globus sensation
PlaceboPlaceboTreatment with placebo in the treatment of globus sensation
Primary Outcome Measures
NameTimeMethod
Clinical remission8 weeks

Proportion of patients in clinical remission or improvement after 8 weeks defined by the Glasgow Edinburgh Throat Scale question 12 ("At present, how annoying do you find your throat sensation?") Ranging from 0-7, where 7 is a worse outcome. Clinical remission is defined as scoring a 0 or 1 on this question.

Secondary Outcome Measures
NameTimeMethod
Overall Treatment Efficacy8 weeks

The Overall Treatment Efficacy evaluation will be analysed by considering the score at 8 weeks. Ranging from 0-6, where 6 is a lower treatment efficacy.

GETS overall scores4 weeks

Improvement of Glasgow Edinburgh Throat Scale overall scores compared between both groups will be evaluated after 4 weeks. The total GETS score is 70, the higher the score, much worse are the symptoms.

Clinical remission4 weeks

Proportion of patients in clinical remission or improvement after 4 weeks defined by the Glasgow Edinburgh Throat Scale question 12 ("At present, how annoying do you find your throat sensation?") Ranging from 0-7, where 7 is a worse outcome. Clinical remission is defined as scoring a 0 or 1 on this question.

Weekly GETS overall scoresweek 1, week 2, week 3, week 4, week 5, week 6, week 7 and week 8

Improvement of Glasgow Edinburgh Throat Scale overall scores compared between both groups evaluated for each week during the treatment period. Ranging from 0-7, where 7 is a worse outcome. Clinical remission is defined as scoring a 0 or 1 on this question.

Trial Locations

Locations (2)

Annelies Geeraerts

🇧🇪

Leuven, Belgium

University Hospital Leuven

🇧🇪

Leuven, België, Belgium

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