Endoscopic Pyloromyotomy for Refractory Gastroparesis

NCT ID: NCT03356067

Last Updated: 2021-01-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-01

Study Completion Date

2021-01-26

Brief Summary

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Gastroparesis is a disorder triggered by numerous causes and it is defined by symptoms and with an objective evidence of delayed gastric emptying in the absence of obstruction.

Effective treatment for gastroparesis is challenging especially in patients with severe symptoms. In refractory gastroparesis, endoscopic or surgical treatments may therefore be considered. Endoscopic treatments include intrapyloric injection of botulinum toxin and transpyloric insertion of a metallic stent. Surgical options involve implantation of a gastric "pacemaker" (gastric stimulation), pyloroplasty and subtotal gastrectomy.

Recently, a new endoscopic technique, gastric endoscopic per oral pyloromyotomy (G-POEM) has been introduced with promising preliminary results.

The aim of this prospective, sham-controlled, cross-over study (cross-over for patients randomized to the sham arm) is to compare short and long-term efficacy and safety of G-POEM in patients with refractory gastroparesis. Symptoms and objective parameters of gastric emptying will be the main outcome criteria. The reason of using a sham protocol is to control for the potential confounders (therapeutic effects of touch and belief, which are components of the placebo effect).

Detailed Description

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Gastroparesis is a disorder triggered by numerous causes and it is defined by symptoms and with an objective evidence of delayed gastric emptying in the absence of obstruction (albeit pyloric spasms may play a role in a subset of patients). Gastroparesis may be a consequence of medication, surgery or diabetes but in approximately one third of patients, the cause remains unknown and the patients are diagnosed with idiopathic gastroparesis. Effective treatment for gastroparesis is challenging especially in patients with severe symptoms. The efficacy of prokinetics is dubious since they have not proven real clinical efficacy in placebo controlled trials. In refractory gastroparesis, endoscopic or surgical treatments may therefore be considered. Endoscopic treatments include intrapyloric injection of botulinum toxin and transpyloric insertion of a metallic stent. Surgical options involve implantation of a gastric "pacemaker" (gastric stimulation), pyloroplasty and subtotal gastrectomy. The partial effectiveness of botulinum toxin injection, stents and pyloroplasty suggests that disruption of the pyloric muscle may lead to a decreased intrapyloric tone and consequently to a symptomatic improvement in some patients with refractory gastroparesis.

Recently, a new endoscopic technique, gastric endoscopic per oral pyloromyotomy (G-POEM) has been introduced with promising preliminary results. Uncontrolled studies with so far limited number of patients have demonstrated a significant symptomatic improvement in approximately 70% of patients and improved or normalized of gastric emptying in more than a half of patients after G-POEM. A prospective uncontrolled study suggested that patients with idiopathic or post-surgical gastroparesis experiences higher success rate after G-POEM (70-80%) compared to patients with diabetic gastroparesis (50%).

G-POEM is, in principle, adaptation of POEM (per-oral endoscopic myotomy) in the stomach. POEM is now considered a standard treatment for esophageal achalasia and it has been shown to be safe and effective. In contrast to achalasia, pathophysiology of pyloric function in patients with gastroparesis is less understood and the explanation of how and why G-POEM should work is some-how hypothetical. For example, presumed pylorospasm has not been demonstrated as the predictive factor for treatment success of G-POEM yet. Refractory gastroparesis is often accompanied by psychological or even psychiatric disturbances and hence a placebo" effect of G-POEM cannot be ruled out. Therefore, the real clinical efficacy of G-POEM can only be demonstrated in a clinical randomized sham-controlled trial.

To assess the severity of gastroparesis-related symptoms, the Gastroparesis Cardinal Symptom Index (GCSI) has been developed for this item. The GCSI is part of a larger questionnaire PAGI-SYM (Patient Assessment of Upper Gastrointestinal Symptom severity index) established for assessment of patient-reported symptoms in gastroparesis (dyspepsia and gastroesophageal reflux). PAGI-SYM as well as GCSI subscale scores varied significantly by global disease severity, with higher (worse) scores observed in those subjects who rated their gastroparesis as moderate to severe.

The aim of this prospective, sham-controlled, cross-over study (cross-over for patients randomized to the sham arm) is to compare short and long-term efficacy and safety of G-POEM in patients with refractory gastroparesis. Symptoms and objective parameters of gastric emptying will be the main outcome criteria. The reason of using a sham protocol is to control for the potential confounders (therapeutic effects of touch and belief, which are components of the placebo effect).

Investigators plan to randomize 86 patients (43 in the active arm, ratio 1:1 active vs. sham). Sample size is calculated based on expected therapeutic success of G-POEM in 50% of patients vs. 20% in the sham group; significance level 0,05; study power 0,8; beta error 0,2; adjustment for 15% expected drop out.

Patients will be randomised in blocks of 6, stratified according to the etiologies: (idiopathic, diabetic, and post-surgical; patients after esophagectomy with gastric pull-through will not be included). Control visits will be scheduled at 3, 6, 12, 24, and 36 months. The primary outcome will be the proportion of patients with treatment success in the active group vs. sham group at 6 months after the procedure. Several secondary outcomes will also be assessed, including procedure-related parameters and safety parameters and change in Gastric Emptying Study (GET) after G-POEM vs. sham. After 6 months, patients randomized to the sham group will be offered G-POEM procedure and further followed up (cross-over part of the study) providing that they did not have a therapeutic effect of the sham procedure.

Conditions

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Gastroparesis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Randomized sham-procedure controlled trial with crossover after 6 months after procedure
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Esophago-gastro-duodenoscopy

Standard endoscopic examination of the upper GI tract with flexible endoscope.

Group Type SHAM_COMPARATOR

Esophago-gastro-duodenoscopy

Intervention Type PROCEDURE

Standard endoscopic examination of the upper GI tract with flexible endoscope

Gastric endoscopic peroral pyloromyotomy

Experimental per-oral endoscopic myotomy of the pyloric sphincter

Group Type EXPERIMENTAL

Gastric endoscopic peroral pyloromyotomy

Intervention Type PROCEDURE

G-POEM is, in principle, adaptation of POEM (per-oral endoscopic myotomy) in the stomach. The procedure consists of:

1. Mucosal incision at the greater curvature 3-5 cm from the pylorus
2. Submucosal tunnelling
3. Finding pyloric sphincter
4. Myotomy (2-3 cm) of the pyloric muscle
5. Incision closure (endoclips or suture device)

Interventions

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Gastric endoscopic peroral pyloromyotomy

G-POEM is, in principle, adaptation of POEM (per-oral endoscopic myotomy) in the stomach. The procedure consists of:

1. Mucosal incision at the greater curvature 3-5 cm from the pylorus
2. Submucosal tunnelling
3. Finding pyloric sphincter
4. Myotomy (2-3 cm) of the pyloric muscle
5. Incision closure (endoclips or suture device)

Intervention Type PROCEDURE

Esophago-gastro-duodenoscopy

Standard endoscopic examination of the upper GI tract with flexible endoscope

Intervention Type PROCEDURE

Other Intervention Names

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G-POEM

Eligibility Criteria

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Inclusion Criteria

* Refractory (\> 6 months) and severe (based on a validated total GSCI = Gastroparesis Cardinal Symptom Index) gastroparesis, with confirmed gastric emptying based on a gastric emptying study: standardized protocol of scintigraphy in all patients (performed less than 4 months prior to enrolment), or confirmed by a validated gastric emptying breath test \[27\]. The total GSCI score must be \>2.3 \[28\].
* Abnormal gastric emptying is defined as retention of Tc-99 m \>60% at 2 h and/or ≥10% of residual activity at 4 h on a standardized sulphur colloid solid-phase gastric emptying study.
* Radiolabelled liquids emptying study will be reserved as alternative technique for patients with poor tolerance of solids during scintigraphy. Abnormal gastric emptying will represent \>50% retention of radiolabelled content (e.g. In-111) at 1 hour.
* Abnormal gastric empyting breath test based on a solid normal range determination for the test used (e.g. T1/2 \> 109 min)

Exclusion Criteria

* Age less than 18 years
* No previous attempt with at least one prokinetic drug
* No previous attempt to withdraw anticholinergic agents and glucagon like peptide -1 (GLP-1) and amylin analogues\* in patients treated with these substances
* Active treatment with opioids or a history of treatment with opioids within 12 months before enrolment.
* Previous gastric surgery BI or II, esophagectomy, gastric pull-through
* Previous pyloromyotomy or pyloroplasty
* Known eosinophilic gastroenteritis
* Organic pyloric (or intestinal) obstruction (fibrotic stricture, etc.)
* Severe coagulopathy
* Esophageal or gastric varices and /or portal hypertensive gastropathy
* Advanced liver cirrhosis (Child B or Child C)
* Active peptic ulcer disease
* Pregnancy or puerperium
* Malignant or pre-malignant gastric diseases (dysplasia, gastric cancer, GIST)
* Any other condition, which in the opinion of the investigator would interfere with study requirements
* Uncontrolled diabetes mellitus
* Diagnosis of rumination syndrome or "eating" disorder (mental anorexia, bulimia nervosa) \*\*
* Severe constipation without using laxatives
* Inability to obtain informed consent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Universitätsklinikum Hamburg-Eppendorf

OTHER

Sponsor Role collaborator

KU Leuven

OTHER

Sponsor Role collaborator

King's College Hospital NHS Trust

OTHER

Sponsor Role collaborator

University Hospital Augsburg

OTHER

Sponsor Role collaborator

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

OTHER

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role collaborator

University of Amsterdam

OTHER

Sponsor Role collaborator

University Hospital Trnava

NETWORK

Sponsor Role collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role collaborator

Comenius University

OTHER

Sponsor Role collaborator

Pavol Jozef Safarik University

OTHER

Sponsor Role collaborator

University of Chicago

OTHER

Sponsor Role collaborator

University of Cluj Napoca

UNKNOWN

Sponsor Role collaborator

Charles University, Czech Republic

OTHER

Sponsor Role collaborator

Institute for Clinical and Experimental Medicine

OTHER_GOV

Sponsor Role lead

Responsible Party

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Doc. (Ass. prof.) Jan Martinek, MD, PhD, AGAF

Ass. prof.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Thomas Rösch, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Hamburg- Eppendorf | UKE Department for Interdisciplinary Endoscopy, Germany

Jan Martinek, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Locations

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University of Chicago

Chicago, Illinois, United States

Site Status

Department of Hepatogastroenterology at Cliniques universitaires St-Luc, Brussels, Belgium

Brussels, , Belgium

Site Status

Translational Research in GastroIntestinal Disorders, Leuven, Belgium

Leuven, , Belgium

Site Status

Institute for Clinical and Experimental Medicine

Prague, Prague, Czechia

Site Status

University Hospital in Hradec Kralove

Hradec Králové, , Czechia

Site Status

The Department of Surgical Gastroenterology L, Denmark

Aarhus, , Denmark

Site Status

III. Medizinische Klinik, Medical Center/Klinikum Augsburg, Germany

Augsburg, , Germany

Site Status

University Medical Center Hamburg- Eppendorf | UKE Department for Interdisciplinary Endoscopy, Germany

Hamburg- Eppendorf, , Germany

Site Status

Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands

Amsterdam, , Netherlands

Site Status

Regional Institute of Gastroenterology

Cluj-Napoca, , Romania

Site Status

Jesenius Faculty of Medicine in Martin, Clinic of Gastroenterological Internal Medicine, Slovak Republic

Martin, , Slovakia

Site Status

Department of Internal Medicine, University Hospital Trnava, Slovak Republic

Trnava, , Slovakia

Site Status

Department of Surgical Gastroenterology, Karolinska University Hospital, Stockholm, Sweden

Stockholm, , Sweden

Site Status

King's Institute of Therapeutic Endoscopy, London, UK

London, , United Kingdom

Site Status

Countries

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United States Belgium Czechia Denmark Germany Netherlands Romania Slovakia Sweden United Kingdom

References

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Martinek J, Hustak R, Mares J, Vackova Z, Spicak J, Kieslichova E, Buncova M, Pohl D, Amin S, Tack J. Endoscopic pyloromyotomy for the treatment of severe and refractory gastroparesis: a pilot, randomised, sham-controlled trial. Gut. 2022 Nov;71(11):2170-2178. doi: 10.1136/gutjnl-2022-326904. Epub 2022 Apr 25.

Reference Type DERIVED
PMID: 35470243 (View on PubMed)

Other Identifiers

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IClinicalEM2

Identifier Type: -

Identifier Source: org_study_id

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