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

A Randomized Controlled Trial Comparing Pregabalin and Placebo in Patients With Persistent Globus Sensation

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

Study Overview

• Status: Recruiting
• Conditions: Globus Sensation
• Intervention / Treatment: Drug: Pregabalin; Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Annelies Geeraerts, MsC; Phone Number: 016343385; Email: Annelies.Geeraerts@kuleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • Annelies Geeraerts
    • Contact: Annelies Geeraerts, PhD student; Phone Number: 01643385; Email: annelies.geeraerts@kuleuven.be
  • België
    • Leuven, België, Belgium, 3000
      • Recruiting
      • University Hospital Leuven
      • Contact: Annelies Geeraerts; Phone Number: +32497671229; Email: annelies.geeraerts@kuleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pregabalin; Treatment with pregabalin in the treatment of globus sensation	Drug: Pregabalin; Patients receive for one week Pregabalin 75 mg and 7 weeks Pregabalin 150 mg; Other Names: Lyrica
Placebo Comparator: Placebo; Treatment with placebo in the treatment of globus sensation	Drug: Placebo; Patients receive a treatment with placebo for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission	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.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GETS overall scores	Improvement of Glasgow Edinburgh Throat Scale (GETS) overall scores compared between both groups will be evaluated after 8 weeks. The total GETS score is 70, the higher the score, much worse are the symptoms.	8 weeks
Clinical remission	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.	4 weeks
GETS overall scores	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.	4 weeks
Overall Treatment Efficacy	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.	8 weeks
Weekly GETS overall scores	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.	week 1, week 2, week 3, week 4, week 5, week 6, week 7 and week 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlations	The correlation between Hospital Anxiety Depression Scale scores, Patient Health Questionnaires scores and therapeutic response evaluated at 8 weeks.	8 weeks
Correlation questionnaires and neuropathy	The correlation between Hospital Anxiety Depression Scale scores, Patient Health Questionnaires scores and neuropathy will be evaluated at 8 weeks. The higher score on the Hospital Anxiety Depression Scale and Patient Health Questionnaire, the worse the patients are feeling: more depressed and more anxious and more somatic complaints.	8 weeks
The impact on upper esophageal manometry.	The impact of active or placebo treatment on manometry at 8 weeks. Specific upper esophageal manometry parameters are not yet defined.	8 weeks

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2010
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: June 21, 2022
• First Submitted That Met QC Criteria: June 21, 2022
• First Posted (Actual): June 27, 2022

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Conversion Disorder; Somatoform Disorders; Globus Sensation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: S52107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No