PSAGS: Pyloric Sphincter Abnormalities in Patients With Gastroparesis Symptoms
Study Details
Study Description
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 three tests to assess the pyloric sphincter - endoluminal functional luminal imaging probe (Endoflip™), electrogastrography (EGG) with water load satiety testing (WLST), and wireless motility capsule (WMC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
There have been several published studies using Endoflip™ to assess the pyloric sphincter in small number of participants. In the first study, Gourcerol et al showed that pyloric compliance is decreased in gastroparesis patients compared to 21 healthy controls and associated with the T1/2 of gastric emptying and symptoms of gastroparesis (Gourcerol 2015). From this study, pyloric distensibility <10 appeared to be abnormal. In the second study, Malik et al found that the pyloric sphincter contour was seen best at distention with 40 cc. Symptoms of early satiety and postprandial fullness were inversely correlated with pyloric diameter and cross-sectional area of the pyloric sphincter (Malik 2015).
Pyloric distensibility <9.2 was associated with improvement in symptoms with endoscopic pyloromyotomy. A recent study showed similar patterns for improvement in symptoms with botulinum toxin injection in the pylorus.
The pyloric sphincter is at the distal end of the stomach, whereas the lower esophageal sphincter (LES) is at the proximal portion of the stomach. How abnormalities of the pyloric sphincter relate to abnormalities of the LES is not known, but will be addressed in this study. Our prior studies have shown that diffuse transit abnormalities may occur in patients with gastroparesis. In addition, patients with gastroparesis can have symptoms of gastroesophageal reflux disease. This study will ascertain if there are LES abnormalities in patients with gastroparesis as determined by Endoflip™, such as LES distensibility and how LES distensibility relates to pyloric distensibility. This study protocol 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 use two additional tests that may assess the pylorus: electrogastrography (EGG) with water load satiety testing (WLST), and wireless motility capsule (WMC).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Symptoms of gastroparesis Participants with symptoms of gastroparesis with minimum GCSI score of 2.0 (18/45 x 5) |
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| Control participants Non-diabetic participant undergoing endoscopy for evaluation but without gastroparesis symptoms or gastroesophageal reflux symptoms. Score 1.0 or less (≤ 1 ) on the GCSI of PAGI-SYM questionnaire |
Outcome Measures
Primary Outcome Measures
- Distensibility of the pylorus [Baseline]
Distensibility of the pylorus will be calculated as the median of three measurements (not three different inflations) of distensibility (mm2/mmHg) of the pylorus pressure using the Endoflip balloon catheter at 50 mL volume
Secondary Outcome Measures
- Opening diameter (mm) of the pylorus when 40 mL volume is introduced into the EF325N Endoflip™ measurement catheter. [Baseline]
diameter (mm) of the pylorus
- Opening diameter (mm) of the pylorus when 50 mL volume is introduced into the EF325N Endoflip™ measurement catheter. [Baseline]
diameter (mm) of the pylorus
- Cross Sectional Area(mm2) of the pylorus with 40 mL balloon volume [Baseline]
Cross Sectional Area (mm2) of the pylorus
- Cross Sectional Area(mm2) of the pylorus with 50 mL balloon volume [Baseline]
Cross Sectional Area (mm2) of the pylorus
- Compliance (mm3/mmHg) of the pylorus with 40 mL balloon volume [Baseline]
Compliance (mm3/mmHg) of the pylorus
- Compliance (mm3/mmHg) of the pylorus with 50 mL balloon volume [Baseline]
Compliance (mm3/mmHg) of the pylorus
- Pressure (mmHg) of the pyloric sphincter [Baseline]
Pressure (mmHg) of the pyloric sphincter
Eligibility Criteria
Criteria
Inclusion Criteria FOR SYMPTOMATIC PARTICIPANTS:
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- 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 21 - 85 4. Symptoms of gastroparesis, either diabetic or idiopathic etiology 5. 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.
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Symptoms of gastroparesis with minimum GCSI score of 2.0 (18/45 x 5) 7. Willingness to:
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Stop taking proton pump inhibitors, cannabinoids, and CBD for 7 days prior to WMC ingestion
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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), and prescription laxatives (e.g. lubiprostone) for 3 days prior to the WMC visit;
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Abstain from prokinetics, cannabinoids and CBD, and 'over the counter' laxatives, isotonic PEG electrolyte preparations (e.g. MiraLax), and prescription laxatives (e.g. lubiprostone, Linzess, Trulance) after ingesting the SmartPill™ until they return for the follow-up visit in 2-5 days. Proton pump inhibitors may be taken 24 hours after SmartPill™ ingestion.
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Abstain from food and water after midnight (at least for 8 hours) before the start of each visit until after the visit.
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Abstain from cannabinoids and CBD (cannabidiol) 7 days before the EGG with water load satiety test INCLUSION CRITERIA FOR CONTROL PARTICIPANTS
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Provision of signed and dated informed consent form
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Male or female, aged 21 or older
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Must not have diabetes.
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Undergoing an upper endoscopy for their clinical evaluation of celiac sprue, diarrhea, GI bleed, or iron-deficiency anemia, Barrett's esophagus, or evaluation for bariatric surgery.
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Do not have upper GI symptoms greater than 1 as assessed by the Gastroparesis Cardinal Symptom Index (GCSI) of PAGI-SYM questionnaire
EXCLUSION CRITERIA:
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- Prior gut lumen surgery on the esophagus or the stomach, including Nissen fundoplication.
- 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:
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Ulcer of the esophagus, stomach, or duodenum
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Esophageal varices 6. Individuals at risk for prolonging the endoscopy procedure: severe chronic pulmonary disease, severe food retention in the stomach on endoscopy 7. Individuals with a history of other chronic disease potentially causative of gastrointestinal symptom: 8. Acute or chronic renal insufficiency 9. Known psychiatric disease 10. Eating disorders 11. Women who are pregnant. A urine pregnancy test is routinely obtained on all females immediately prior to endoscopic procedures and ingestion of the wireless motility capsule.
- Individuals with contraindications for endoscopy, including bleeding abnormalities
- Allergy to eggs preventing sedation with propofol 14. Allergy to wheat preventing ingestion of the SmartBar 15. Significant dysphagia 16. Prior inflammatory bowel disease 17. Prior diverticulitis 18. History of gastric bezoar 19. History of Crohn's disease 20. Chronic frequent NSAID use 21. Cardiac medical devices (insulin pumps, continuous glucose monitors are permitted) 22. Presence or prior use of gastric stimulator 23. History of any gastric/pyloric injection of botulinum toxin
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Louisville | Louisville | Kentucky | United States | 40202 |
| 2 | Johns Hopkins Hospital | Baltimore | Maryland | United States | 21287 |
| 3 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 4 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
| 5 | Temple University | Philadelphia | Pennsylvania | United States | 19140 |
| 6 | Texas Tech University Health Science Center (TTUHSC) | El Paso | Texas | United States | 79905 |
Sponsors and Collaborators
- Johns Hopkins Bloomberg School of Public Health
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Johns Hopkins University
- Massachusetts General Hospital
- Temple University
- University of Louisville
- Wake Forest University
- Texas Tech University Health Sciences Center, El Paso
Investigators
- Study Chair: Pankaj Pasricha, MD, Johns Hopkins University
- Study Chair: Henry Parkman, MD, Temple University
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- Fisher R, Cohen S. Physiological characteristics of the human pyloric sphincter. Gastroenterology. 1973 Jan;64(1):67-75.
- Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology. 1986 Jun;90(6):1919-25.
- 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. Review.
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