Clinical trial NCT05432843: Comparing Pregabalin and Placebo in Patients With Persistent Globus Sensation
Official title: A Randomized Controlled Trial Comparing Pregabalin and Placebo in Patients With Persistent Globus Sensation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Globus Sensation
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2022-06-27
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel design with open label period
Primary purpose: TREATMENT

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.

Eligibility criteria: 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,

Primary outcomes:
measure: Clinical remission
timeFrame: 8 weeks
Secondary outcomes:
measure: GETS overall scores
timeFrame: 8 weeks
measure: Clinical remission
timeFrame: 4 weeks
measure: GETS overall scores
timeFrame: 4 weeks
measure: Overall Treatment Efficacy
timeFrame: 8 weeks
measure: Weekly GETS overall scores
timeFrame: week 1, week 2, week 3, week 4, week 5, week 6, week 7 and week 8
Other outcomes:
measure: Correlations
timeFrame: 8 weeks
measure: Correlation questionnaires and neuropathy
timeFrame: 8 weeks
measure: The impact on upper esophageal manometry.
timeFrame: 8 weeks
Locations:
city: Leuven
country: Belgium
facility: University Hospital Leuven
state: België
city: Leuven
country: Belgium
facility: Annelies Geeraerts
Study officials:
References: