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Endoscopic Pyloromyotomy for Refractory Gastroparesis (GREG)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03356067
Recruitment Status : Completed
First Posted : November 29, 2017
Last Update Posted : January 27, 2021
Sponsor:
Collaborators:
Universitätsklinikum Hamburg-Eppendorf
KU Leuven
King's College Hospital NHS Trust
University Hospital Augsburg
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Karolinska Institutet
University of Amsterdam
University Hospital Trnava
Rigshospitalet, Denmark
Comenius University
Pavol Jozef Safarik University
University of Chicago
University of Cluj Napoca
Charles University, Czech Republic
Information provided by (Responsible Party):
Doc. (Ass. prof.) Jan Martinek, MD, PhD, AGAF, Institute for Clinical and Experimental Medicine

Tracking Information
First Submitted Date  ICMJE October 27, 2017
First Posted Date  ICMJE November 29, 2017
Last Update Posted Date January 27, 2021
Actual Study Start Date  ICMJE December 1, 2017
Actual Primary Completion Date December 24, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 22, 2017)
Main outcome is the proportion of patients with treatment success after the procedure. [ Time Frame: 6 months ]
Treatment success is defined as a decrease of a total Gastroparesis Cardinal Symptom Index (GCSI) symptom score at least 50% from the baseline
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2017)
  • Proportion of patients with treatment success in the active arm after 3 months [ Time Frame: 3 months ]
    Treatment success is defined as a decrease of a total Gastroparesis Cardinal Symptom Index (GCSI) symptom score at least 50% from the baseline
  • Proportion of patients with treatment success in the active arm after 12 months [ Time Frame: 12 months ]
    Treatment success is defined as a decrease of a total Gastroparesis Cardinal Symptom Index (GCSI) symptom score at least 50% from the baseline
  • Proportion of patients with treatment success in the active arm after 24 months [ Time Frame: 24 months ]
    Treatment success is defined as a decrease of a total Gastroparesis Cardinal Symptom Index (GCSI) symptom score at least 50% from the baseline
  • Proportion of patients with treatment success in the active arm after 36 months [ Time Frame: 36 months ]
    Treatment success is defined as a decrease of a total Gastroparesis Cardinal Symptom Index (GCSI) symptom score at least 50% from the baseline
  • Proportion of patients with treatment success in the sham group at 3M [ Time Frame: 3 months ]
    Treatment success is defined as a decrease of a total Gastroparesis Cardinal Symptom Index (GCSI) symptom score at least 50% from the baseline
  • Change in Gastroparesis Cardinal Symptom Index (GCSI) before and after G-POEM at 3, 6, 12, 24 and 36M and before vs. after sham procedure at 3M and 6M; [ Time Frame: 3, 6, 12, 24 and 36 months ]
    Comparison of the change of the scores between the active and sham groups.
  • Change in The Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) before and after G-POEM at 3, 6, 12, 24 and 36M and before vs. after sham procedure at 3M and 6M; [ Time Frame: 3, 6, 12, 24 and 36 months ]
    Comparison of the change of the scores between the active and sham groups.
  • Proportion of crossed-over patients with treatment success after 6 moths [ Time Frame: 12 months ]
    Treatment success is defined as a decrease of a total GSCI symptom score at least 50% from the baseline
  • Change in Gastroparesis Cardinal Symptom Index (GCSI) crossed-over patients after the G-POEM procedure [ Time Frame: 12 months ]
    Comparison of the change of the scores pre and post-procedure
  • Change in The Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) in crossed-over patients after the G-POEM procedure [ Time Frame: 12 months ]
    Comparison of the change of the scores pre and post-procedure
  • Subgroup post-hoc analyses of the treatment success and change in symptomatic scores according to etiology of gastroparesis. [ Time Frame: 3, 6, 12, 24 and 36 months ]
    Treatment success is defined as a decrease of a total GSCI symptom score at least 50%, change in GCSI and PAGY-SYM scores
  • Change in gastric emptying (scintigraphy) study and/or gastric emptying breath test before and after both G-POEM and sham procedure [ Time Frame: 3, 6, 12, 24 and 36 months ]
    Comparison of the mean change of these parameters between active and sham groups.
  • Procedure details [ Time Frame: 1 month ]
    length of the procedure
  • Procedural adverse events [ Time Frame: 1 month ]
    perioperative adverse events (complications)
  • Long term adverse events [ Time Frame: 3, 6, 12, 24 and 36 months ]
    Incidence rate of adverse events in treatment and sham groups
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Endoscopic Pyloromyotomy for Refractory Gastroparesis
Official Title  ICMJE A Randomized, Sham and Cross-Over-Controlled Trial of Per-oral Endoscopic Pyloromyotomy (G-POEM) in Patients With Refractory Gastroparesis
Brief Summary

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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Randomized sham-procedure controlled trial with crossover after 6 months after procedure
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Gastroparesis
Intervention  ICMJE
  • Procedure: 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)
    Other Name: G-POEM
  • Procedure: Esophago-gastro-duodenoscopy
    Standard endoscopic examination of the upper GI tract with flexible endoscope
Study Arms  ICMJE
  • Sham Comparator: Esophago-gastro-duodenoscopy
    Standard endoscopic examination of the upper GI tract with flexible endoscope.
    Intervention: Procedure: Esophago-gastro-duodenoscopy
  • Experimental: Gastric endoscopic peroral pyloromyotomy
    Experimental per-oral endoscopic myotomy of the pyloric sphincter
    Intervention: Procedure: Gastric endoscopic peroral pyloromyotomy
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 26, 2021)
42
Original Estimated Enrollment  ICMJE
 (submitted: November 22, 2017)
86
Actual Study Completion Date  ICMJE January 26, 2021
Actual Primary Completion Date December 24, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Czechia,   Denmark,   Germany,   Netherlands,   Romania,   Slovakia,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03356067
Other Study ID Numbers  ICMJE IClinicalEM2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Doc. (Ass. prof.) Jan Martinek, MD, PhD, AGAF, Institute for Clinical and Experimental Medicine
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Institute for Clinical and Experimental Medicine
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Universitätsklinikum Hamburg-Eppendorf
  • KU Leuven
  • King's College Hospital NHS Trust
  • University Hospital Augsburg
  • Cliniques universitaires Saint-Luc- Université Catholique de Louvain
  • Karolinska Institutet
  • University of Amsterdam
  • University Hospital Trnava
  • Rigshospitalet, Denmark
  • Comenius University
  • Pavol Jozef Safarik University
  • University of Chicago
  • University of Cluj Napoca
  • Charles University, Czech Republic
Investigators  ICMJE
Principal Investigator: Thomas Rösch, MD, PhD University Medical Center Hamburg- Eppendorf | UKE Department for Interdisciplinary Endoscopy, Germany
Principal Investigator: Jan Martinek, MD, PhD Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
PRS Account Institute for Clinical and Experimental Medicine
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP