PPI's and SSRI's Therapy for the Management of NCCP (NCCP)

November 27, 2019 updated by: Nikos Viazis, Evangelismos Hospital

Proton Pump Inhibitor (PPI's) and Selective Serotonin Reuptake Inhibitor Therapy (SSRI's) for the Management of Non Cardiac Chest Pain (NCCP)

Non cardiac chest pain (NCCP) is defined as recurring, angina-like, retrosternal chest pain of non cardiac origin. Annual prevalence of NCCP in the general population of the western world ranges from 25-35%. Of those patients presenting to an emergency room with chest pain, a cardiac etiology is ultimately found in only 11-39%. Several conditions are associated with NCCP, with gastroesophageal reflux disease (GERD) being the most prevalent, constituting up to 60% of cases. However, NCCP is considered a disorder of heterogenous nature and several other conditions, apart of GERD, such as esophageal dysmotility and esophageal hypersensitivity have been implicated.

Treatment of NCCP remains a real challenge due to the diverse underlying mechanisms responsible for patients' symptoms. Given the fact that GERD is by far the most common etiology, proton pump inhibitor (PPI) therapy has been tried extensively; however, after 6 weeks of treatment complete resolution of symptoms occurs in only 30% of patients, the optimal duration of PPI administration is not known, while the best maintenance dose has never been determined. Although the administration of selective serotonin reuptake inhibitors (SSRIs) could theoretically benefit those patients with esophageal hypersensitivity, the trials that have been published so far have included small number of patients and reported conflicting results, while the co-administration of PPIs with SSRIs has not been evaluated so far. Furthermore, data on treatment of patients with functional chest pain are lacking.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

We have therefore designed a prospective study in order to evaluate the effect of PPI and SSRI therapy for different subtypes of NCCP patients using multichannel intraluminal impedance and pH (MII-pH) monitoring.

METHODS

Patients with non cardiac chest pain symptoms presenting to the participating centres, will be prospectively screened for entry into the study.

They should have undergone a comprehensive diagnostic evaluation by cardiologists in order to exclude a cardiac source for their chest pain. Patients recruited in the study should have either a normal coronary angiogram or lack of ischemic heart disease on exercise treadmill or stress thallium testing

Inclusion criteria i) patients should have at least 3 episodes of chest pain per week in the previous 3 months.

The exclusion criteria will be:

i) thoracic, esophageal or gastric surgery ii) primary or secondary esophageal motility disorders iii) use of non-steroidal anti-inflammatory drugs and aspirin iv) presence of Barrett's esophagus, erosive esophagitis, peptic stricture and duodenal or gastric ulcer on upper endoscopy v) eosinophilic esophagitis vi) underlying psychiatric illness vii) pregnancy in women viii) refusal to participate.

Study protocol

All subjects who will agree to participate in the study should undergo an upper endoscopy to assess the presence or absence of esophageal mucosal injury. Patients with Barrett's esophagus and erosive esophagitis will not be included in the present study. Furthermore, biopsies will be taken and patients with eosinophilic esophagitis will also be excluded.

All patients will also be subjected to stationary esophageal manometry and those with motility abnormalities will be excluded. During esophageal manometry the lower esophageal sphincter (LES) will be located.

Esophageal impedance-pH monitoring will be performed in all participating subjects using an ambulatory multichannel intraluminal impedance (MII) and pH monitoring system (Sleuth; Sandhill Scientific, Inc. Higland Ranch, CO, USA). During the test, each subject will eat three standard meals, while the beginning and ending times of every meal will be indicated in a diary. Subjects will also be instructed to press the event marker button on the data logger whenever they experience chest pain. Data recording will be concluded after 24 hours, when patients will return to the endoscopy unit for the catheter removal.

The impedance and pH data will be used to determine in each patient the number and type of reflux episodes and the total 24-hour esophageal acid exposure, defined as the total time at pH below 4 divided by the time monitoring. Total distal esophageal acid exposure (i.e., % time pH < 4) less than 4.2% over 24 hours will be considered normal.

In each patient we will calculate the symptom index (SI) for chest pain. Bioview analysis software will be used for the calculation of SI. According to the setting of this software the symptoms will be considered as being related to reflux if they occur within a 2-min time window after the onset of the reflux episode. SI will be defined as the number of symptoms associated with reflux divided by the total number of symptoms. A positive SI is declared if ≥ 50% (i.e, at least half of the symptoms are associated with reflux).

Treatment

Patients will abnormal distal acid esophageal exposure will receive PPI twice daily for 8 weeks .

Patients with positive symptom index for chest pain will receive citalopram 20 mg once daily and PPI once daily for 8 weeks.

Patients with a negative symptom index for chest pain will receive citalopram 20mg once daily for 8 weeks.

All patients will be evaluated at the end of the 8-week period and will be asked about the presence or absence of chest pain. Treatment success will be defined as the complete disappearance of the chest pain, while the presence of mild or infrequent symptoms will be considered as treatment failure.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
    • Attiki
      • Athens, Attiki, Greece, 10676
        • Evangelismos Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients should have at least 3 episodes of chest pain per week in the previous 3 months. Meanwhile they should have undergone a comprehensive diagnostic evaluation by cardiologists in order to exclude a cardiac source for their chest pain. Patients recruited in the study should have either a normal coronary angiogram or lack of ischemic heart disease on exercise treadmill or stress thallium testing.

Exclusion Criteria:

The exclusion criteria will be: i) a history of thoracic, esophageal or gastric surgery, ii) primary or secondary esophageal motility disorders, iii) use of non-steroidal anti-inflammatory drugs and aspirin, iv) presence of Barrett's esophagus, erosive esophagitis, peptic stricture and duodenal or gastric ulcer on upper endoscopy, v) eosinophilic esophagitis, vi) underlying psychiatric illness, vii) pregnancy in women, viii) refusal to participate.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: GERD with PPI's therapy
Patients will abnormal distal acid esophageal exposure will receive PPI twice daily for 8 weeks .
Active Comparator: PPI's and SSRI's therapy
Patients with positive symptom index for chest pain will receive citalopram 20 mg once daily and PPI once daily for 8 weeks.
Drug: Citalopram
Other Names:
  • Proton Pump Inhibitor
Active Comparator: SSRI's therapy
Patients with a negative symptom index for chest pain will receive citalopram 20mg once daily for 8 weeks
Drug: Citalopram
Other Names:
  • Proton Pump Inhibitor

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
complete disappearance of the chest pain
Time Frame: at the end of the 8-week period of therapy.
at the end of the 8-week period of therapy.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Evangelismos Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 3, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 6, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 7, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 2, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 27, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EvangelismosH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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