Clinical trial NCT03865290: Effects of Ondansetron on Gastrointestinal Sensorimotor Dysfunctions in Diabetes Mellitus and Dyspepsia
Official title: Effects of Ondansetron on Gastrointestinal Sensorimotor Dysfunctions in Diabetes Mellitus and Dyspepsia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Indigestion
Diabetes Mellitus
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2019-03-06
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Researchers are trying to understand why people with indigestion and diabetes mellitus have gastrointestinal symptoms and in particular to understand whether symptoms are related to increased sensitivity to nutrients in the small intestine. As part of this investigation, a medication called ondansetron will also be studied to determine its effects on gastrointestinal function and associated symptoms.

Detailed description: The primary objectives of this study are to evaluate the effects of ondansetron, on symptoms (i) during a gastric emptying study, (ii) during enteral lipid infusion and (iii) in daily life.

Eligibility criteria: Inclusion Criteria:

* Healthy male or non-pregnant, non-breastfeeding female volunteers;
* 18-75 years old;
* Able to provide written informed consent before participating in the study
* Able to communicate adequately with the investigator and to comply with the requirements for the entire study; including the willingness and ability to consume the components of the test meals
* Symptoms of dyspepsia (i.e., early satiety, postprandial discomfort, nausea, vomiting, regurgitation)
* Patients in the DM group will also require Type 1 or 2 DM of ≥ 3 years duration; in patients with type 2 DM, the dyspepsia symptoms should have begun or worsened after DM was diagnosed

Exclusion Criteria:

* Major abdominal surgery (i.e., appendectomy, cholecystectomy, tubal ligation, hysterectomy, herniorrhaphy, and limited colonic resection are permissible)
* Clinical evidence (including physical exam and EKG) of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric or other disease that may interfere with the objectives of the study and/or pose safety concerns
* Current use of opiates, alpha adrenergic agonists, metoclopramide, monoamine oxidase inhibitors, more than one serotonergic medication, and high doses of anticholinergic agents (eg, amitriptyline greater than 50 mg daily). If medically safe, these drugs may be discontinued for four half lives prior to study assessments.
* Treatment with GLP-1 agonists and amlyin which cause vagal blockade and may affect central processing of pain
* Bleeding or clotting disorders or medications that increase risk of bleeding from mucosal biopsies
* Positive tissue transglutaminase antibodies (TTG),
* Pregnant or breast-feeding females
* Known intolerance or allergy to eggs
* Poor peripheral venous access, if central venous access is not available
* Any other condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study
* History of Long QT Syndrome or prolonged QT interval (i.e., corrected QT interval \> 480 ms)
* Current symptoms of a functional gastrointestinal disorder assessed by questionnaire
* Severe vomiting that would preclude tube placement or participation in the study
* Structural cause for symptoms by endoscopy within the past 12 months
* Patients with gastric pacemakers

Primary outcomes:
measure: Change in severity of symptoms during enteral infusion
timeFrame: baseline, every 15 minutes up to 8 hours
measure: Change in severity of symptoms during gastric emptying study
timeFrame: baseline, every 15 minutes up to 2 hours
measure: Change in severity of daily symptoms
timeFrame: Baseline, daily for six weeks
measure: Change in severity of gastrointestinal symptoms
timeFrame: Baseline, 2 weeks, 6 weeks
measure: Change in severity of gastrointestinal symptoms effect on Quality of Life
timeFrame: Baseline, 2 weeks, 6 weeks
measure: Change in effect of Gastrointestinal symptoms on Quality of Life
timeFrame: Baseline
Secondary outcomes:
measure: Glucose level
timeFrame: baseline, approximately 60-120 minutes
measure: Insulin level
timeFrame: baseline, approximately 60-120 minutes
measure: C-peptide level
timeFrame: baseline, approximately 60-120 minutes
measure: Glucagon-like Peptide 1 (GLP-1)
timeFrame: baseline, approximately 60-120 minutes
measure: Cholecystokinin (CCK)
timeFrame: baseline, approximately 60-120 minutes
measure: Ghrelin
timeFrame: baseline, approximately 60-120 minutes
measure: Peptide YY (PYY)
timeFrame: baseline, approximately 60-120 minutes
measure: Plasma
timeFrame: baseline, approximately 60-120 minutes
measure: Effect of gastrointestinal symptoms on Quality of Life - Nepean Dyspepsia index
timeFrame: Baseline
measure: Severity of gastrointestinal symptoms - Nepean Dyspepsia index
timeFrame: Baseline
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Adil E Bharucha, MD
role: PRINCIPAL_INVESTIGATOR
References: