Chest Pain Rule Out Myocardial InfarctionPhase 4NCCPNCT02825342
PPI's and SSRI's Therapy for the Management of NCCP
A Phase 4 study testing Citalopram in people with Chest Pain Rule Out Myocardial Infarction, run by Evangelismos Hospital at 1 site in Greece.
Trial summary
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%. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Chest Pain Rule Out Myocardial Infarction
- What is being tested?
- Citalopram
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteGreece
- Study dates
- Mar 2014to Dec 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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:
- 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.
- Being tested
- Citalopram
- Keywords
- Gastroesophageal Reflux Disease (GERD), Proton Pump Inhibitor (PPI)
- Medical subject headings
- Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CitalopramDrug
Also called Proton Pump Inhibitor
| Study group | Role | What they receive |
|---|---|---|
| GERD with PPI's therapy | No intervention | Patients will abnormal distal acid esophageal exposure will receive PPI twice daily for 8 weeks . |
| PPI's and SSRI's therapy | Active comparator | Patients with positive symptom index for chest pain will receive citalopram 20 mg once daily and PPI once daily for 8 weeks. Receives: Drug: Citalopram |
| SSRI's therapy | Active comparator | Patients with a negative symptom index for chest pain will receive citalopram 20mg once daily for 8 weeks Receives: Drug: Citalopram |
What is being measured
The primary outcome is the main question the study is designed to answer.
complete disappearance of the chest pain
Measured: at the end of the 8-week period of therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2016 (estimated)
- Study startMar 2014
- Primary completionAug 2017
- Study completionDec 2017
Why it stopped: Primary endpoint was reached.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chest Pain Rule Out Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Evangelismos Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nikos Viazis, Evangelismos Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02825342
- Sponsor's protocol ID
- EvangelismosH
- Acronym
- NCCP
- Status last verified
- Nov 2019
- First submitted
- 3 Jul 2016
- Last updated
- 2 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proton Pump Inhibitor (PPI's) and Selective Serotonin Reuptake Inhibitor Therapy (SSRI's) for the Management of Non Cardiac Chest Pain (NCCP)
- ClinicalTrials.gov ID
- NCT02825342
- Acronym / sponsor ID
- NCCP / EvangelismosH
- Keywords
- Gastroesophageal Reflux Disease (GERD), Proton Pump Inhibitor (PPI)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Primary endpoint was reached.
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Evangelismos HospitalUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Aug 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 7 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| GERD with PPI's therapy | No intervention | –Patients will abnormal distal acid esophageal exposure will receive PPI twice daily for 8 weeks . |
| PPI's and SSRI's therapy | Active comparator | Drug: CitalopramPatients with positive symptom index for chest pain will receive citalopram 20 mg once daily and PPI once daily for 8 weeks. |
| SSRI's therapy | Active comparator | Drug: CitalopramPatients with a negative symptom index for chest pain will receive citalopram 20mg once daily for 8 weeks |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CitalopramAlso: Proton Pump Inhibitor | Drug | PPI's and SSRI's therapy, SSRI's therapy |
Primary outcome
complete disappearance of the chest pain
Time frame: at the end of the 8-week period of therapy.
Results and safety
The study was stopped early (reason given: Primary endpoint was reached.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Citalopram in people with Chest Pain Rule Out Myocardial Infarction, run by Evangelismos Hospital at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Primary endpoint was reached.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
complete disappearance of the chest pain (time frame: at the end of the 8-week period of therapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2019.