Clinical trial NCT03904004: Pressure and Flow Study Before and After Treatments for EMD. The pFlow Study
Official title: Impact of Peroral Endoscopic Myotomy and Other Treatments for Oesophageal Motility Disorders on Bolus Transport and Gastro-oesophageal Reflux. The pFlow Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Esophageal Motility Disorders
Gastro-esophageal Reflux
Keywords: esophageal motility disorders
laparoscopic Heller myotomy
peroral endoscopic myotomy
neumatic cilatation
botulinic toxin injection
gastro esophageal reflux
Lead sponsor: Fundacion Miguel Servet
Sponsor class: OTHER
First posted: 2019-04-04
Enrollment: 60
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients of any age and sex diagnosed with an EMD that generate symptoms

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Bolus Pressure and Flow (PF) modification
timeFrame: 6 months
Secondary outcomes:
measure: PF analysis within similar OMD
timeFrame: 6 months
measure: Symptom correlation
timeFrame: 12 months
measure: Clinical success correlation
timeFrame: 12 months
measure: Correlation with barium column
timeFrame: 6 months
measure: Correlation with reflux
timeFrame: 6 months
Other outcomes:
Locations:
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
Study officials:
affiliation: Complejo Hospitalario de Navarra
name: Fermin Estremera-Arevalo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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