Clinical trial NCT04661215: Pyloric Sphincter Abnormalities in Patients With Gastroparesis Symptoms
Official title: Pyloric Sphincter Abnormalities in Patients With Gastroparesis Symptoms
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Gastroparesis
Idiopathic Gastric Motility Disorder
Diabetic Gastroparesis
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Massachusetts General Hospital
name: Temple University
name: University of Louisville
name: Wake Forest University
name: Texas Tech University Health Sciences Center, El Paso
name: Mayo Clinic
First posted: 2020-12-10
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will be 150 adult men and women aged 18-85 years, located in the United States, 100 will have symptoms of gastroparesis, and 50 participants in the control group will be patients undergoing upper endoscopy for clinical evaluation of diarrhea, gastrointestinal (GI) bleed, or iron-deficiency anemia, or evaluation for bariatric surgery who do not have upper GI symptoms greater than 1 as assessed by the Gastroparesis Cardinal Symptom Index (GCSI) . Control group participants will not have Gastric Alimetry testing or water load satiety testing.

Brief summary: The overall objective of this study is to determine if there are pyloric sphincter abnormalities in patients with gastroparesis symptoms and determine how prevalent these abnormalities are using tests to assess the pyloric sphincter - endoluminal functional luminal imaging probe (Endoflip™), water load satiety testing (WLST), and high-resolution cutaneous electrogastrography (HR-EGG) using Gastric Alimetry™ System.

Detailed description: Study Description: This is a multi-center, prospective, observational study to assess pyloric sphincter abnormalities in patients with symptoms of gastroparesis (both delayed and normal gastric emptying) and control participants without symptoms of gastroparesis using the commercially available, FDA approved endoluminal functional luminal imaging probe (Endoflip™) catheter, which measures diameter, cross-sectional area, pressure, compliance, and distensibility of gastrointestinal sphincter muscles.

This study will assess lower esophageal and pyloric sphincter diameter, CSA, pressure, distensibility, and compliance in patients with symptoms of gastroparesis and delayed gastric emptying, patients with symptoms of gastroparesis but with normal gastric emptying, and normal control participants. The protocol will also include a water load satiety test and use Gastric Alimetry™ System that assesses gastric myoelectrical activity in symptomatic participants but not control participants.

Eligibility criteria: Inclusion Criteria FOR SYMPTOMATIC PARTICIPANTS:

1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Male or female, aged 18-85
4. Symptoms of gastroparesis, either diabetic or idiopathic etiology
5. Symptoms of gastroparesis with minimum Gastroparesis Cardinal Symptom Index (GCSI) score of 2.0 (18/45 x 5)
6. Individual will have had a prior 4-hour gastric emptying scintigraphy test performed for clinical evaluation within the last 6 months. This gastric emptying test would be done for clinical evaluation and is not part of the research study. From these participants with gastroparesis symptoms, we will include those with delayed gastric emptying as well as those with normal gastric emptying.
7. Participant must not initiate any new treatments until completion of the study procedures.
8. Willingness to:

   1. Stop histamine 2 antagonists, prokinetics (e.g., metoclopramide, erythromycin, domperidone, prucalopride), narcotics, anticholinergics, constipation medications (over the counter laxatives, isotonic polyethylene glycol (PEG) electrolyte preparations (e.g. MiraLax), prescription laxatives (e.g. lubiprostone), proton pump inhibitors, cannabinoids, and cannabidiol (CBD) for 3 days prior to each visit;
   2. Abstain from food and water after midnight (at least for 8 hours) before the start of each visit until after the visit.

INCLUSION CRITERIA FOR CONTROL PARTICIPANTS

1. Provision of signed and dated informed consent form
2. Male or female, aged 18 or older
3. Undergoing an upper endoscopy for their clinical evaluation of diarrhea, GI bleed, or iron-deficiency anemia, or evaluation for bariatric surgery.
4. Do not have upper GI symptoms greater than 1 as assessed by the Gastroparesis Cardinal Symptom Index (GCSI) of PAGI-SYM questionnaire.

EXCLUSION CRITERIA:

1. Prior gut lumen surgery on the esophagus or the stomach, including Nissen fundoplication.
2. Prior surgery on the pylorus (G-POEM, surgical pyloroplasty, surgical pyloromyotomy)
3. Known history of achalasia or esophageal stricture
4. Known history of physiological or mechanical GI obstruction
5. Abnormalities seen on a prior upper endoscopy placing patient at increased risk:

   * Ulcer of the esophagus, stomach, or duodenum
   * Esophageal varices
6. Individuals at risk for prolonging the endoscopy procedure: severe chronic pulmonary disease, severe food retention in the stomach on endoscopy.
7. Presence of significant gastric or duodenal pathology that could be expected to cause dysmotility (e.g. significant inflammation, infiltrate disorders etc)
8. Individuals with a history of other chronic disease potentially causative of gastrointestinal symptom
9. Acute or chronic renal insufficiency
10. Current eating disorders
11. Females who are pregnant. A urine pregnancy test is routinely obtained on all females immediately prior to endoscopic procedures.
12. Individuals with contraindications for endoscopy, including bleeding abnormalities
13. Allergy to eggs preventing sedation with propofol and/or gastric emptying test
14. Significant dysphagia
15. Prior inflammatory bowel disease, Crohn's
16. History of any esophageal/gastric/pyloric injection of botulinum toxin
17. Patients on daily opioid use or \>3 day/week use
18. Use of glucagon-like peptide 1 (GLP1) receptor agonists or Sodium-Glucose Transport Protein 2 (SGLT2); Gastric inhibitory polypeptide (GIP)- glucagon-like peptide (GLP) combo

Primary outcomes:
measure: Distensibility of the pylorus
timeFrame: Baseline
Secondary outcomes:
measure: Opening diameter (mm) of the pylorus when 40 mL volume is introduced into the EF325N Endoflip™ measurement catheter.
timeFrame: Baseline
measure: Opening diameter (mm) of the pylorus when 50 mL volume is introduced into the EF325N Endoflip™ measurement catheter.
timeFrame: Baseline
measure: Cross Sectional Area(mm2) of the pylorus with 40 mL balloon volume
timeFrame: Baseline
measure: Cross Sectional Area(mm2) of the pylorus with 50 mL balloon volume
timeFrame: Baseline
measure: Compliance (mm3/mmHg) of the pylorus with 40 mL balloon volume
timeFrame: Baseline
measure: Compliance (mm3/mmHg) of the pylorus with 50 mL balloon volume
timeFrame: Baseline
measure: Pressure (mmHg) of the pyloric sphincter
timeFrame: Baseline
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General
state: Massachusetts
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: El Paso
country: United States
facility: Texas Tech University Health Science Center (TTUHSC)
state: Texas
Study officials:
affiliation: Mayo Clinic
name: Pankaj Pasricha, MD
role: STUDY_CHAIR
affiliation: Temple University
name: Henry Parkman, MD
role: STUDY_CHAIR
References:
citation: Fisher R, Cohen S. Physiological characteristics of the human pyloric sphincter. Gastroenterology. 1973 Jan;64(1):67-75. No abstract available.
citation: Parkman HP, Hasler WL, Fisher RS; American Gastroenterological Association. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004 Nov;127(5):1592-622. doi: 10.1053/j.gastro.2004.09.055.
citation: Desipio J, Friedenberg FK, Korimilli A, Richter JE, Parkman HP, Fisher RS. High-resolution solid-state manometry of the antropyloroduodenal region. Neurogastroenterol Motil. 2007 Mar;19(3):188-95. doi: 10.1111/j.1365-2982.2006.00866.x.
citation: Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology. 1986 Jun;90(6):1919-25. doi: 10.1016/0016-5085(86)90262-3.