Heartburn Clinical Trial
Official title:
What is the Physiologic and Clinical Relevance of Oesophagogastric Junction Distensibility? Studies Using Endo-Flip and 96 Hour Wireless pH System
Monitoring oesophageal pH provides a definitive diagnosis of patients with
gastro-oesophageal reflux disease (GORD), especially those in whom the association between
reflux and symptoms is uncertain and those under consideration for anti-reflux surgery.
Standard ambulatory investigation is normally performed by naso-oesophageal catheter however
this is associated with considerable discomfort and in turn altered behaviour which reduces
reflux provoking activities. Furthermore results of catheter based ambulatory pH studies are
compromised by the high variability of acid exposure in patients with suspected GORD.
Prolonging pH measurements by the catheter-free Bravo™ system from 24 to 48 and 96hrs
significantly improves the consistency (reliability) and reproducibility of diagnoses based
on oesophageal acid exposure, as well as the ability to associate acid reflux to symptom
episodes. This improves diagnosis especially in those with intermittent symptoms.
However pH monitoring does not provide a direct assessment of the underlying
pathophysiology. Incompetence of the oesophago-gastric junction (OGJ) related to disruption
of its structure and function is considered to be the most important cause of GORD. A more
relevant assessment of the reflux barrier may be its distensibility (i.e. the ease with
which the OGJ is opened to allow retrograde passage of gastric contents); however this is
not assessed by current clinical investigations.
Endo-FLIP (Crospon Medical Devices) is a new tool which assesses OGJ structure and function,
and appears to provide relevant information regarding its distensibility and competence.
This study applies to using Endo-Flip to record OGJ distensibility and Bravo to record acid
exposure and symptom association in patients with reflux symptoms. The variability of pH
measurements and symptoms and diagnostic accuracy will be assessed over 96hrs. Endo-FLIP
results will then be compared against Bravo. The outcome of post investigation therapy will
then be compared with Endo-Flip and Bravo results to assess if baseline testing can predict
the outcome of acid suppression therapy.
Study Hypothesis
1. There is a positive, continuous association between OGJ distensibility measured by
Endo-FLIP on % acid exposure assessed by prolonged Bravo pH monitoring
2. The results of Endo-FLIP and prolonged Bravo predict treatment outcome of a trial of
proton pump inhibitor therapy
This is a single centre study of patients (n=60) referred for investigation of reflux
symptoms. Each patient is investigated by Endo-FLIP™, endoscopy, and 96 hour Bravo™ pH
monitoring off acid suppressant medication.
After calibration the Endo-FLIP catheter will be inserted orally or nasally until the
liquid-filled compliant bag at the distal segment of the catheter (which houses 16 impedance
sensors) straddles the OGJ. Stepwise bag distensions of 10, 20 and 30 ml will then be
conducted and the associated intra-bag pressure measured. The Endo-FLIP display will allow
real-time imaging of OGJ intra-luminal geometry during distension. Intra-bag pressure and
CSA at the impedance planimetry segment best localized within the OGJ will be reported as
mean ± SEM.
An endoscopy will then be performed to confirm the position of the squamo-columnar junction
(SCJ). Images will be taken of the SCJ using standard white light and narrow band imaging.
Then 2 x 2 biopsies from the SCJ and 2 cm proximally will be taken. In conclusion, the
Bravo® delivery system will be passed orally with the patient lying in the left lateral
decubitus position and the capsule will be deployed 6 cm proximal to the SCJ after 1 minute
of suction to stabilize the position.
After 2 measurements for 48 hours (separated by a battery change) the patient will return
the receiver for the final download and analysis. In addition to pH measurement and symptom
documentation during the 96hr period, pepsin lateral flow tests (Technostics, Hull, UK) will
be performed by collecting expectorated saliva on returning to the lab on day 2 and day 4.
Patients will also be provided with two further kits to be used if and when they experience
symptoms during the 4 day study.
The primary outcome assessment of oesophageal acid exposure will be percent time pH<4 over
the measurement period (e.g. 24, 48 or 96h). Other parameters that will be analysed are the
number of reflux events and the association of these events with symptoms recorded on the
Bravo™ receiver. The presence or absence of pepsin in expectorated saliva will also be
assessed.
All subjects will complete a quality of life assessment (SF-36). Symptom severity will be
assessed at baseline and at follow-up and will be documented by validated questionnaires
(Eraflux) before and after resumption of routine acid reducing therapy. Those that undergo
anti-reflux surgery will also be followed up at 3 and 6 months.
LOS distensibility measurements using Endo-FLIP will also be collected in those diagnosed
with achalasia on manometry in order to be used as reference values for the Bravo study.
Patient symptoms will be reviewed at baseline off treatment and again after six weeks of
returning back onto their standard acid reducing medication. Patients referred for
anti-reflux surgery will be reviewed 3 and 6 months after the procedure.
This is a prospective study of 60 consecutive patients referred for the investigations
typical reflux symptoms (power calculations to allow comparison of 24hr vs. 48hr pH
testing).
Analysis
Bravo:
1. Retrospective analysis: Formal statistical analysis of the pH and symptom database that
was collected prospectively over the last 4 years (contains >200 Bravo pH studies).
This will establish the correlation between pH results from 24, 48 and 96hr monitoring
with clinical variables (e.g. severity of reflux symptoms, symptom association) and
outcome (e.g. response to PPI, response to fundoplication).
2. Prospective analysis: The day-to-day variability of pH measurements will be calculated.
Patients will be classified by acid exposure (abnormal: >4.2% time pH<4) and symptom
index (positive SI: >50% association of reflux events and any symptom) during each 24hr
and 48hr test period. The reproducibility and accuracy of 24hr vs. 48hr pH testing will
be assessed with 96hr results as the reference standard.
Endo-Flip: Stepwise bag distensions of 10, 20 and 30 ml will be conducted and the associated
intra-bag pressure measured. The Endo-FLIP display will allow real-time imaging of OGJ
intraluminal geometry during distension. The primary outcome assessment of OGJ
distensibility will be the intra-bag pressure and cross-sectional area at the impedance
planimetry segment best localized within the LOS as mean ± SEM for each consecutive volume
distension. The correlation of OGJ distensibility with oesophageal acid exposure will then
be assessed.
The correlation and interaction between OGJ distensibility, acid exposure, reflux-symptom
association and symptom characteristics (e.g. severity and predominant symptom) at baseline
and on treatment will be assessed by co-variant regression analysis.
;
Observational Model: Case Control, Time Perspective: Prospective
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