Pressure and Flow Study Before and After Treatments for EMD. The pFlow Study

Esophageal Motility Disorders Clinical Trial

— pFlow  

Official title:

Impact of Peroral Endoscopic Myotomy and Other Treatments for Oesophageal Motility Disorders on Bolus Transport and Gastro-oesophageal Reflux. The pFlow Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03904004
• Other study ID #: EST-ALB-pFlow
• Status: Not yet recruiting
• Start date: May 15, 2019
• Est. completion date: June 2022

Study information

• Verified date: April 2019
• Source: Fundacion Miguel Servet
• Contact: Fermin Estremera-Arevalo, MD, PhD
• Phone: +34 686255456
• Email: festremera15[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Pressure and flow (PF) analysis allow a detailed report on the bolus passing for each segment of the esophagus. This approach has evidence in oropharyngeal dysphagia, post reflux surgery dysphagia, gastroesophageal reflux in infants and dysphagia in patients with normal manometry. However, it has not been used for defined esophageal motility disorders and their response to surgical or endoscopic treatments. Better knowledge about pre and postoperative bolus flow can yield important concepts that can modify the selection of optimal treatments.

Description:

Methods This is an international multicenter prospective observational study in a cohort of individuals affected by an oesophageal motor disorder (OMD).

Participating centers OMD are treated in most tertiary hospitals surgically (Laparoscopic Heller Myotomy (LHM)) or endoscopically (botulinic toxin injection, pneumatic dilatation or peroral endoscopic myotomy (POEM)). The main requirement is to perform high-resolution manometry with impedance before and after the procedure.

Subjects Inclusion criteria are to present with gastrointestinal (GI) symptoms that are secondary to OMD such as dysphagia, regurgitation and/or non-cardiac chest pain. OMD under study are achalasia type I, II and III; oesophagogastric junction (OGJ) outflow obstruction; distal oesophageal spasm, hypercontractile oesophagus or disorders not fulfilling Chicago Criteria version 3. Treatments included are outlined in the previous paragraph.

Exclusion criteria are the inability to fill in symptom questionnaires, intolerance of pre or postprocedure test, incomplete therapeutic procedures or artifacts in manometry/impedance tracings.

Data sharing High-resolution manometry (HRM)-impedance studies will be shared and PF analysis will be performed through Swallow Gateway®. See Appendix 1 for further detail. An acrobat sheet will be eased to fill-in symptomatic and test data pre and post-procedure. It will also be shared through Swallowgateway®.

Variables

1. Demographics: age, sex, anesthetic risk assessment (ASA), height and weight, proton pump inhibitors (PPI) intake.

2. Previous treatments:

1. Type of treatment.

2. Number of previous treatments.

3. Years before current treatment.

3. Symptoms: time from symptoms onset, dysphagia scores (Eckardt, Mellow-Pinkas), gastro-esophageal reflux score questionnaire (GERD-Q), heartburn and regurgitation visual analogic score (VAS), quality of life score short form 12 (SF-12).

4. Pre and post-operative test:

1. Endoscopy: sigmoid oesophageal dilatation, solid/liquid oesophageal remanent, difficulty to progress through OGJ, oesophagitis (Los Angeles score).

2. Barium swallow: oesophageal diameter [grade I (< 3.5 cm), grade II (3.5-6 cm) and grade III (> 6 cm)]14, barium column height at 1 and 5 min post-swallowing.

3. High-resolution manometry: equipment specification (probe, system), morphologic classification of the OGJ, end-expiratory basal pressure, 4 second integrated relaxation pressure (4s-IRP), mean distal contractile integrity (DCI), percentage of failed swallows (DCI<100 mmHg-cm-s), distal latency (DL), percentage of swallows with distal oesophagus pressurization > 30 mmHg, percentage of swallows with pan oesophageal pressurization, type of peristalsis after rapid swallow test, pan oesophageal pressurization after multiple swallow test. Chicago v3 diagnosis of motility pattern.

5. Procedure variables:

a. Botulinic toxine: i. International units (IU) delivered. ii. Number of toxine injection sessions. iii. Region of oesophagus where the toxin is injected. iv. Complications description, severity and management*. b. Pneumatic dilatation: i. Size of the balloon. ii. Number of dilatations. iii. Complications description, severity and management *. iv. In-hospital stay length**. c. POEM: i. Number of POEM performed by the endoscopist. ii. Anterior or posterior approach. iii. Oesophageal tunnel length. iv. Gastric tunnel length. v. Oesophageal myotomy length. vi. Gastric myotomy length. vii. Full-thickness or partial myotomy. viii. Duration of the procedure. ix. Complications description, severity and management *. x. In-hospital stay length**. d. Laparoscopic Heller Myotomy: i. Number of LHM performed by the surgeon. ii. Oesophageal myotomy length. iii. Gastric myotomy length. iv. Duration of the procedure. v. Complications description, severity and management*. vi. In-hospital stay length**.

6. Pre and post-operative pressure-flow analysis in HRM-impedance:

• HRM-impedance protocol: patient preparation and HRIM catheter insertion are recommended as described previously (see references) in a recumbent and an inclination of 0 to 30 degrees of head elevation. After positioning of the probe sensors and a 5-min rest period, swallow-induced peristalsis will be tested at 30s intervals. Ten 5-mL liquid swallows (0.9% saline) will be delivered. Peristalsis recovery (weak or normal peristalsis in > 1 swallow with normal DL).

a. Three measures of intra-bolus distension pressures (DP) during bolus transport were determined at nadir impedance7. These pressures were i. DP bolus accommodation (DPA), intra-bolus distension pressure recorded between the upper oesophageal sphincter (UOS) and the transition zone (TZ); ii. DP compartmentalized transport (DPCT), intra-bolus distension pressure recorded between the TZ and the contractile deceleration point, (CDP); and iii. DP during oesophageal emptying (DPE), intra-bolus distension pressure recorded between the CDP and crural diaphragm (CD).

b. Bolus clearance from the oesophagus was determined by the impedance ratio (IR = oesophageal nadir impedance divided by impedance recorded during contractile peak pressure). Higher IR indicates less effective oesophageal clearance16.

c. Two measures of bolus flow latencies, determined at the CDP level, were i. swallow initiation to maximal bolus distension latency (SDL) and ii. maximal bolus distension to contraction latency (DCL). d. Pressures generated during bolus clearance (or clearance pressures) were measured within the distal oesophagus. The closure pressure (CP) was the pressure at luminal closure and the rate of ramp pressure (RP) was the mean gradient of pressure during closure. Timing of luminal closure was taken as when impedance had recovered 50 %, a validated criterion in widespread use17.

e. A pressure-flow index (PFI) composite score was derived using the following formula:

PFI = (DPE*RP)/DCL i.e. the distal IBP during the phase of oeosphageal emptying multiplied by the rate of ramp pressure rise, divided by the time interval from bolus distension to contraction latency.

f. Bolus presence time (BPT) was estimated based on the method of Lin within the 2 cm segment above the CD landmark.

g. Trans-OGJ bolus flow time (BFT) was calculated also according to the method of Lin, recording the time deemed favourable for bolus flow across the OGJ.

7. 24h pH/impedance testing.

• Following American Society for gastrointestinal endoscopy (ASGE) lexicon. **Days after finishing the procedure.

Analysis Main outcome

1. Compare the modification of PF variables between the type of treatment groups for the same OMD.

Secondary outcomes

1. Comparison of pre-procedure PF variables within patients diagnosed with the same manometric subtype.

2. Correlation of PF variables before and after treatment with the respective symptoms.

3. Comparison of post-procedure PF variables between patients with clinical success and clinical failure.

4. Correlation of post-procedure PF variables with barium column.

5. Comparison of post-procedure PF variables between patients with and without post-procedure GOR.

6. Correlation of post-procedure PF variables with grade of Los Angeles oesophagitis classification, % of distal oesophageal acid exposure time and deMeester score.

Visits protocol Visit 1 - at pre-procedure HRM impedance

• Delivery of informed consent.

• Demographic and symptomatic data interrogation.

• Gather endoscopy and barium swallow data.

• HRM impedance testing.

• Procedure choice and explanation. Visit 2 - at hospital discharge

• Procedure-related variables.

• Complications.

• In-hospital stay length. Visit 3 - 3 to 6 months post-procedure

• Symptom-related data.

• Endoscopy and barium swallow data.

• HRM impedance testing.

• 24h pH/impedance testing.

• Data sharing through Swallow Gateway®. Visit 4 - 1 year post-procedure

• Symptomatic data interrogation

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: June 2022
• Est. primary completion date: May 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• to present with GI symptoms that are secondary to EMD such as dysphagia, regurgitation and/or non-cardiac chest pain.

• the EMD patients to be recruited under this study are achalasia type I, II and III; OGJ outflow obstruction; distal oesophageal spasm, hypercontractile oesophagus or disorders not fulfilling Chicago Criteria v3.

• Receive a treatment such as POEM, neumatic dilatation, LHM, botox injection.

Exclusion Criteria:

• Exclusion criteria are the inability to fill in symptom questionnaires, intolerance of pre or post procedure test, incomplete therapeutic procedures or technical failure of baseline manometry investigation

Related Conditions & MeSH terms

• Esophageal Motility Disorders
• Esophageal Spasm, Diffuse
• Esophagitis, Peptic
• Gastro-esophageal Reflux
• Gastroesophageal Reflux

Intervention

Procedure:
• Peroral endoscopic myotomy
Endoscopic myotomy after performing a tunnel to reach the muscular layer through a mucosal incision
• Neumatic dilatation
Inflation of a ballon of specific diameter in the gastro-oesophageal junction
• Botulinum toxin injection
Injection of botulinic toxin to inhibit the contraction of the gastro-oesophageal junction muscular layer
• Laparoscopic Heller Myotomy
Five or six small incisions are made in the abdominal wall and laparoscopic instruments are inserted. The myotomy is a lengthwise cut along the oesophagus, starting above the lower oesophageal sphincter (LOS) and extending down onto the stomach a little way. The oesophagus is made of several layers, and the myotomy only cuts through the outside muscle layers which are squeezing it shut, leaving the inner mucosal layer intact.

Locations

Country	Name	City	State
Spain	Complejo Hospitalario de Navarra	Pamplona	Navarra

Sponsors (1)

Lead Sponsor	Collaborator
Fundacion Miguel Servet

Country where clinical trial is conducted

Spain, 

References & Publications (21)

Bredenoord AJ, Hebbard GS. Technical aspects of clinical high-resolution manometry studies. Neurogastroenterol Motil. 2012 Mar;24 Suppl 1:5-10. doi: 10.1111/j.1365-2982.2011.01830.x. Review. — View Citation

Eckardt VF, Aignherr C, Bernhard G. Predictors of outcome in patients with achalasia treated by pneumatic dilation. Gastroenterology. 1992 Dec;103(6):1732-8. — View Citation

Estremera-Arévalo F, Albéniz E, Rullán M, Areste I, Iglesias R, Vila JJ. Efficacy of peroral endoscopic myotomy compared with other invasive treatment options for the different esophageal motor disorders. Rev Esp Enferm Dig. 2017 Aug;109(8):578-586. doi: 10.17235/reed.2017.4773/2016. Review. — View Citation

Imam H, Shay S, Ali A, Baker M. Bolus transit patterns in healthy subjects: a study using simultaneous impedance monitoring, videoesophagram, and esophageal manometry. Am J Physiol Gastrointest Liver Physiol. 2005 May;288(5):G1000-6. — View Citation

Inoue H, Minami H, Kobayashi Y, Sato Y, Kaga M, Suzuki M, Satodate H, Odaka N, Itoh H, Kudo S. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy. 2010 Apr;42(4):265-71. doi: 10.1055/s-0029-1244080. Epub 2010 Mar 30. — View Citation

Jones R, Junghard O, Dent J, Vakil N, Halling K, Wernersson B, Lind T. Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther. 2009 Nov 15;30(10):1030-8. doi: 10.1111/ — View Citation

Kahrilas PJ, Bredenoord AJ, Fox M, Gyawali CP, Roman S, Smout AJ, Pandolfino JE; International High Resolution Manometry Working Group. The Chicago Classification of esophageal motility disorders, v3.0. Neurogastroenterol Motil. 2015 Feb;27(2):160-74. doi: 10.1111/nmo.12477. Epub 2014 Dec 3. — View Citation

Kane ED, Budhraja V, Desilets DJ, Romanelli JR. Myotomy length informed by high-resolution esophageal manometry (HREM) results in improved per-oral endoscopic myotomy (POEM) outcomes for type III achalasia. Surg Endosc. 2019 Mar;33(3):886-894. doi: 10.1007/s00464-018-6356-0. Epub 2018 Jul 27. — View Citation

Khashab MA, Familiari P, Draganov PV, Aridi HD, Cho JY, Ujiki M, Rio Tinto R, Louis H, Desai PN, Velanovich V, Albéniz E, Haji A, Marks J, Costamagna G, Devière J, Perbtani Y, Hedberg M, Estremera F, Martin Del Campo LA, Yang D, Bukhari M, Brewer O, Sanaei O, Fayad L, Agarwal A, Kumbhari V, Chen YI. Peroral endoscopic myotomy is effective and safe in non-achalasia esophageal motility disorders: an international multicenter study. Endosc Int Open. 2018 Aug;6(8):E1031-E1036. doi: 10.1055/a-0625-6288. Epub 2018 Aug 10. — View Citation

Lin Z, Imam H, Nicodème F, Carlson DA, Lin CY, Yim B, Kahrilas PJ, Pandolfino JE. Flow time through esophagogastric junction derived during high-resolution impedance-manometry studies: a novel parameter for assessing esophageal bolus transit. Am J Physiol — View Citation

Lundell LR, Dent J, Bennett JR, Blum AL, Armstrong D, Galmiche JP, Johnson F, Hongo M, Richter JE, Spechler SJ, Tytgat GN, Wallin L. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999 Aug;45(2):172-80. — View Citation

Mellow MH, Pinkas H. Endoscopic therapy for esophageal carcinoma with Nd:YAG laser: prospective evaluation of efficacy, complications, and survival. Gastrointest Endosc. 1984 Dec;30(6):334-9. — View Citation

Myers JC, Nguyen NQ, Jamieson GG, Van't Hek JE, Ching K, Holloway RH, Dent J, Omari TI. Susceptibility to dysphagia after fundoplication revealed by novel automated impedance manometry analysis. Neurogastroenterol Motil. 2012 Sep;24(9):812-e393. doi: 10.1 — View Citation

Nguyen NQ, Holloway RH, Smout AJ, Omari TI. Automated impedance-manometry analysis detects esophageal motor dysfunction in patients who have non-obstructive dysphagia with normal manometry. Neurogastroenterol Motil. 2013 Mar;25(3):238-45, e164. doi: 10.11 — View Citation

Omari T, Connor F, McCall L, Ferris L, Ellison S, Hanson B, Abu-Assi R, Khurana S, Moore D. A study of dysphagia symptoms and esophageal body function in children undergoing anti-reflux surgery. United European Gastroenterol J. 2018 Jul;6(6):819-829. doi: — View Citation

Omari TI, Dejaeger E, Van Beckevoort D, Goeleven A, De Cock P, Hoffman I, Smet MH, Davidson GP, Tack J, Rommel N. A novel method for the nonradiological assessment of ineffective swallowing. Am J Gastroenterol. 2011 Oct;106(10):1796-802. doi: 10.1038/ajg. — View Citation

Omari TI, Papathanasopoulos A, Dejaeger E, Wauters L, Scarpellini E, Vos R, Slootmaekers S, Seghers V, Cornelissen L, Goeleven A, Tack J, Rommel N. Reproducibility and agreement of pharyngeal automated impedance manometry with videofluoroscopy. Clin Gastr — View Citation

Omari TI, Szczesniak MM, Maclean J, Myers JC, Rommel N, Cock C, Cook IJ. Correlation of esophageal pressure-flow analysis findings with bolus transit patterns on videofluoroscopy. Dis Esophagus. 2016 Feb-Mar;29(2):166-73. doi: 10.1111/dote.12300. Epub 201 — View Citation

Schlottmann F, Luckett DJ, Fine J, Shaheen NJ, Patti MG. Laparoscopic Heller Myotomy Versus Peroral Endoscopic Myotomy (POEM) for Achalasia: A Systematic Review and Meta-analysis. Ann Surg. 2018 Mar;267(3):451-460. doi: 10.1097/SLA.0000000000002311. — View Citation

Singendonk MM, Kritas S, Cock C, Ferris LF, McCall L, Rommel N, van Wijk MP, Benninga MA, Moore D, Omari TI. Pressure-flow characteristics of normal and disordered esophageal motor patterns. J Pediatr. 2015 Mar;166(3):690-6.e1. doi: 10.1016/j.jpeds.2014.1 — View Citation

Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220-33. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bolus Pressure and Flow (PF) modification	Compare oesophageal biomechanics (based on PF analysis) before and after the different surgical or endoscopic treatments for oesophageal motility disorders (OMD). This analysis describes through numeric variables the passing of the bolus from the mouth to the stomach regarding resistance of flow, clearance and velocity for every part of the oesophagus	6 months
Secondary	PF analysis within similar OMD	Compare PF variables (as described in Outcome 1) within the same OMD at the moment previously to the treatment.	6 months
Secondary	Symptom correlation	Correlate PF variables with pre and post-treatment symptoms of dysphagia, chest pain, regurgitation and heartburn symptom scoring.	12 months
Secondary	Clinical success correlation	Identify PF variables that may be predictors with clinical success and failure as described in the symptom scoring tests.	12 months
Secondary	Correlation with barium column	Identify PF variables that are predictors of timed barium column as a surrogate of prognosis	6 months
Secondary	Correlation with reflux	Identify PF variables that are predictors of post-procedure gastro-oesophageal reflux (GOR) diagnosis after endoscopy - regarding oesophagitis- and 24h pH test -regarding percentage of distal oesophagus acid exposure and deMeester score.	6 months

External Links

•   Online tool for sharing manometry studies and performing P&F analysis