Ignite Creation Date:
2024-05-06 @ 8:48 AM
Last Modification Date:
2024-10-26 @ 12:05 PM
Study NCT ID:
NCT02825342
Status:
TERMINATED
Last Update Posted:
2019-12-02
First Post:
2016-07-03
Brief Title:
PPIs and SSRIs Therapy for the Management of NCCP
Sponsor:
Evangelismos Hospital
Organization:
Evangelismos Hospital
Study Overview
Official Title:
Proton Pump Inhibitor PPIs and Selective Serotonin Reuptake Inhibitor Therapy SSRIs for the Management of Non Cardiac Chest Pain NCCP
Status:
TERMINATED
Status Verified Date:
2019-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Primary endpoint was reached
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NCCP
Brief 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 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
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
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 Barretts 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 Barretts 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 ie time pH 4 less than 42 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 ie 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
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 Barretts 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 Barretts 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 ie time pH 4 less than 42 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 ie 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None