Citalopram for Reflux Hypersensitivity and Functional Heartburn

A Placebo-controlled Trial With Citalopram for the Treatment of Typical Reflux Symptoms in Patients With Reflux Hypersensitivity or Functional Heartburn With Incomplete Proton Pump Inhibitor Response

Citalopram is a drug used in the treatment of depressive episodes and belongs to the group of selective serotonin reuptake inhibitors (SSRI). Serotonin is an important neurotransmitter predominantly found in the brain and the gastrointestinal tract. Serotonin is associated with psychological disorders, including anxiety and depression, and emotion regulation and it has been shown that anxiety and depression are associated with increased severity of GERD-related symptoms. Citalopram and other SSRI's elevate the concentration of serotonin by blocking the reabsorption into the presynaptic neuron and thereby increasing the level of serotonin available to bind the postsynaptic receptor. A recent study showed beneficial effects of citalopram in patients with reflux hypersensitivity. However, there was no objective measurement for reflux nor esophageal sensitivity during the treatment period. Moreover, the effect of citalopram in patients with functional heartburn has not been studied so far. Therefore, the inevestigators will conduct a randomized, parallel, placebo-controlled study to evaluate the efficacy of citalopram on the improvement in symptom severity, reflux parameters and esophageal sensitivity. 50 patients with reflux hypersensitivity and 50 patients with functional heartburn will receive either placebo or citalopram (Cipramil®) 20 mg as an add-on for a period of 8 weeks. Symptom severity will be assessed by a validated reflux questionnaire (ReQuest questionnaire and diaries), reflux parameters by performing a 24 hour impedance-pH monitoring and esophageal sensitivity using the multimodal esophageal stimulation paradigm

Study Overview

• Status: Unknown
• Conditions: GERD
• Intervention / Treatment: Drug: Citalopram 20mg; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hannelore Geysen; Phone Number: +32 (0)16 324921; Email: hannelore.geysen@kuleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Contact: Hannelore Geysen; Phone Number: +32 (0)16 324921; Email: hannelore.geysen@kuleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 to 65 years old.
2. History of typical GERD symptoms during PPI treatment, at least 3 times per week for 12 weeks.
3. Daily intake of PPI treatment 12 weeks prior to inclusion, with at least 8 weeks of b.i.d. therapy (at least 2*20mg of omeprazole or equivalent).
4. 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.
5. 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:

1. Endoscopic signs of severe erosive esophagitis (≥ grade B, Los Angeles classification) on endoscopy performed during PPI treatment in the 6 months prior to screening.
2. Systemic diseases, known to affect esophageal motility.
3. Surgery in the thorax or in the upper part of the abdomen (appendectomy and cholecystectomy are allowed).
4. QT c>450 ms
5. Treatment with SSRI's prior to the start of the study.
6. Concomitant use of medications such as: anticholinergics, tricycle antidepressants, baclofen and prokinetics.
7. Significant neurological, respiratory, hepatic, renal, hematological, cardiovascular, metabolic or gastrointestinal cerebrovascular disease as judged by the investigator.
8. Major psychiatric disorder.
9. Absence of PPI intake for at least 2 consecutive days in the 2 weeks prior to the screening.
10. Pregnancy or breast feeding.
11. History of poor compliance. History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent.
12. 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
Experimental: Citalopram; 20mg, once a day	Drug: Citalopram 20mg; Citalopram is taken once a day as an add-on to PPI treatment (2x/d).
Placebo Comparator: Placebo; Once a day	Drug: Placebo Oral Tablet; Placebo is taken once a day as an add-on to PPI treatment (2x/d)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in number of reflux episodes	The primary efficacy endpoint will be the change in number of reflux episodes assessed by 24 hour impedance-pH monitoring.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in reflux parameters	change in reflux parameters (number of reflux episodes with a high proximal extent, volume exposure) assessed by 24 hour impedance-pH monitoring,	8 weeks
change in esophageal sensitivity	change in esophageal sensitivity assessed by multimodal esophageal stimulation procedure	8 weeks
change in symptom severity	change in symptom severity assessed by validated reflux questionnaires (ReQuest questionnaire and diaries). Patients will have to indicate the symptom occurence and symptom severity on a scale. Two words, on each site of the scale indicate their symptom severity (on the left "totally not present" on the right "very strong present"). A higher score represents a worse outcome.	8 weeks

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2019
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: April 11, 2018
• First Submitted That Met QC Criteria: April 11, 2018
• First Posted (Actual): April 17, 2018

Study Record Updates

• Last Update Posted (Actual): December 5, 2019
• Last Update Submitted That Met QC Criteria: December 4, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Signs and Symptoms, Digestive; Hypersensitivity; Heartburn; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: S61111

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