A Placebo Controlled Trial With Baclofen for the Treatment of GERD Patients With Incomplete PPI Response

Reflux (acid and non-acid) mainly occurs during transient LES relaxations (TLESRs). The gamma-aminobutyric acid (GABA) receptor type B agonist baclofen was shown to inhibit TLESRs, thereby significantly decreasing acid reflux after a meal in healthy controls and in patients with GERD.

The primary objective of this study is to assess the efficacy (assessed by reflux symptom questionnaire and pH-impedance recordings) of baclofen 10mg three times daily vs. placebo in GERD patients with an incomplete response to PPI therapy.

The secondary objective is to assess the predictive value of reflux assessment (by pH-impedance recordings) on the primary outcome.

Study Overview

• Status: Completed
• Conditions: Gastro Esophageal Reflux
• Intervention / Treatment: Drug: Baclofen; Other: Placebos

Detailed Description

This is a randomized, parallel, double-blind, placebo-controlled, out-patient, single-center study. Eligible subjects will be randomly assigned to receive either oral baclofen 10 mg or placebo t.i.d for a period 4 weeks. After 4 weeks all patients will be given the standard dose of baclofen 10 mg t.i.d. (open label), for another 4 weeks. The b.i.d. PPI therapy will be continued for the entire study duration.

Approximately 90 evaluable subjects with typical GERD symptoms (heartburn and/or regurgitation) will participate in this study and will be randomized on a 1:1 basis: 45 subjects each will be in the placebo and baclofen 10 mg three times daily group. Subjects will be considered to have completed the study if they complete the week 4 visit.

Medication will consist of identically-looking capsules of baclofen or placebo. Patients will take 1 capsule containing 5 mg baclofen with meals t.i.d for 7 days and then 1 capsule containing 10 mg baclofen with meals t.i.d for the remaining 21 days.

Prior to visit 1, all subjects included in the study will undergo a 24 hr pH-impedance study which was requested by the treating physician. This investigation is part of the standard clinical work up and will not be part of the study protocol.

Informed consent is to be signed and dated by the subject before any study related procedures are performed. The date of each visit to the clinic and the date and time of the last dose of test article will be recorded.

Throughout the study patients will be asked to complete daily a short questionnaire (ReQuest) for reflux symptoms.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 - 75 years old
• History of typical (heartburn/regurgitation) or atypical GERD symptoms during PPI treatment, at least 3 times per week for 12 weeks. Daily intake of PPI treatment 12 weeks prior to inclusion.
• Sexually active women of child bearing potential participating in the study must use a medically acceptable form of contraception. Medically acceptable forms of contraception include oral contraceptives, injectable or implantable methods, intrauterine devices, or properly used barrier contraception.
• Subjects must be capable of understanding and be willing to provide signed and dated written voluntary informed consent before any protocol-specific screening procedures are performed.

Exclusion Criteria:

• Endoscopic signs of severe erosive esophagitis (≥ grade C, Los Angeles classification) on endoscopy performed during PPI treatment in the 6 months prior to screening.
• Systemic diseases, known to affect esophageal motility.
• Surgery in thorax or in the upper part of the abdomen.
• Treatment with baclofen prior to the start of the study.
• Regular use of medications such as: anticholinergics, tricycle antidepressants.
• Significant neurological, respiratory, hepatic, renal, haematological, cardiovascular, metabolic or gastroinestinal cerebrovascular disease as judged by the investigator
• Absence of PPI intake for at least 2 consecutive days in the 2 weeks prior to the screening.
• Pregnancy or breast feeding.
• History of poor compliance. History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent. (well-compensated depression is allowed).
• History of alcohol or drug abuse that would interfere with ability to comply with protocol requirements.

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: baclofen arm; baclofen 10mg tid for 4 weeks	Drug: Baclofen; baclofen 10mg tid for 4 weeks; Other Names: Lioresal
Placebo Comparator: placebos arm; placebo tid for 4 weeks	Other: Placebos; placebo tid for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy of baclofen on reflux symptom questionnaire	To assess the effect of baclofen on reflux symptom questionnaire by ReQuest	Change from baseline in ReQuest scores at 4 weeks
efficacy of baclofen on pH-impedance recordings	To assess of baclofen on 24 hour pH-impedance recordings	Change from baseline in reflux parameters (total number of reflux episodes) on 24h pH-impedance monitoring at 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive value of the reflux monitoring	To assess the predictive value of the 24 hour pH-impedance monitoring (symptom association probability = SAP) on the primary outcome	Is SAP at baseline predictor of response at 4 weeks

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Jan Tack, PhD, MD, UZ Leuven

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2010
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: February 4, 2019
• First Submitted That Met QC Criteria: February 7, 2019
• First Posted (Actual): February 8, 2019

Study Record Updates

• Last Update Posted (Actual): February 8, 2019
• Last Update Submitted That Met QC Criteria: February 7, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; GABA Agents; Neuromuscular Agents; Muscle Relaxants, Central; GABA Agonists; GABA-B Receptor Agonists; Baclofen
• Other Study ID Numbers: S51996

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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