Gastrointestinal Sensorimotor Dysfunctions in Diabetes Mellitus
Condition: Dyspepsia; Diabetes Mellitus With Gastrointestinal Symptoms
MeSH terms: Diabetes Mellitus; Dyspepsia
Intervention: Exendin 9-39; Microlipid; Placebo
Intervention description: Exendin 9-39 will be administered intravenously (1,200 pmol/kg bolus followed by infusion at 300 pmol/kg/min).; Lipid infusion {66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).; Normal saline infusion will be prepared to match the appearance of Exendin 9-39
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to understand why people with indigestion have gastrointestinal
      symptoms and in particular to understand whether symptoms are related to increased
      sensitivity to nutrients in the small intestine and to a hormone (GLP1) which is normally
      released from the small intestine in response to nutrients. We propose to study the
      contribution of GLP1 to intestinal sensitivity with a drug (exendin 9-39) that blocks the
      effects of GLP1.
    

Eligibility criteria:

        Inclusion criteria for controls:

          -  Healthy male or non-pregnant, non-breastfeeding female volunteers;

          -  18-70 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

        Additional inclusion criteria for patients:

          -  Symptoms of dyspepsia (i.e., early satiety, postprandial discomfort, nausea, vomiting,
             regurgitation)

          -  Patients in the Diabetes Mellitus (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 - for patients and controls:

          -  Major abdominal surgery (i.e., appendectomy, cholecystectomy, tubal ligation,
             hysterectomy, 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

          -  Opiates, alpha adrenergic agonists, metoclopramide, and high doses of anticholinergic
             agents (e.g., amitriptyline greater than 50 mg daily). If medically safe, these drugs
             may be discontinued for four half lives prior to study assessments

          -  Treatment with glucagon-like peptide-1 (GLP-1) agonists and amylin which cause vagal
             blockade and may affect central processing of pain

          -  Use of tobacco products within the past six months or NSAIDs or aspirin within the
             past week (since they all may affect intestinal permeability)

          -  Bleeding or clotting disorders or medications that increase risk of bleeding from
             mucosal biopsies

          -  Positive tissue transglutaminase antibodies (TTG)

          -  For two days prior to studies, subjects will be instructed to avoid ingestion of
             artificial sweeteners such as sucralose (SplendaTM), aspartame (NutrasweetTM), foods
             containing lactulose or mannitol

          -  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

        Exclusion criteria for controls only:

        • Current symptoms of a functional gastrointestinal disorder assessed by questionnaire

        Exclusion criteria for patients only:

          -  Severe vomiting that would preclude tube placement or participation in the study

          -  Structural cause for symptoms by endoscopy within the past 48 months

          -  Patients with gastric pacemakers