Gastrointestinal Sensorimotor Dysfunctions in Diabetes Mellitus

NCT02170870 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 14-002098P01DK068055
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Dyspepsia; Diabetes Mellitus With Gastrointestinal Symptoms

Outcome Measures

Primary Outcomes (1)

• Mean Intestinal Chemosensitivity to Lipids Perfusion

  Intestinal chemosensitivity was recorded by evaluating symptoms during duodenal lipid infusion (0.5 gm/mL diluted in water to 222 mL) and placebo or the glucagon like peptide 1 (GLP-1) receptor antagonist exendin 9-39 over 2 hours. Participants reported the severity of 6 symptoms (nausea, fullness, bloating, abdominal pain, belching, and burning) at 15 minute intervals using a Visual Analogue Scale (VAS) marked 0 (minimum value) - 4 (maximum value): absent (0), light (1), moderate (2), severe (3) and intolerable(4). The scores recorded for nausea, fullness, bloating, and abdominal pain over the 2 hour infusion were averaged and reported as the mean symptom score. Higher scores mean a worse outcome.

  Day 1, approximately 2 hours after infusion

Secondary Outcomes (1)

• Rate of Gastric Emptying (GE t 1/2) in Patients With Diabetes Mellitus (DM) or Non-ulcer Dyspepsia (NUD) Compared to Placebo

  Day 1

Study Arms (6)

Healthy Controls Exendin 9-39

EXPERIMENTAL

Exendin 9-39 was 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).

Drug: Exendin 9-39; Drug: Microlipid

Healthy Controls Placebo

PLACEBO COMPARATOR

Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).

Drug: Microlipid; Drug: Placebo

Diabetics Exendin 9-39

EXPERIMENTAL

Exendin 9-39 was 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).

Drug: Exendin 9-39; Drug: Microlipid

Diabetics Placebo

PLACEBO COMPARATOR

Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).

Drug: Microlipid; Drug: Placebo

Functional Dyspepsia Exendin 9-39

EXPERIMENTAL

Exendin 9-39 was 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).

Drug: Exendin 9-39; Drug: Microlipid

Functional Dyspepsia Placebo

PLACEBO COMPARATOR

Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).

Drug: Microlipid; Drug: Placebo

Interventions

Exendin 9-39 DRUG

Exendin 9-39 will be administered intravenously (1,200 pmol/kg bolus followed by infusion at 300 pmol/kg/min).

Diabetics Exendin 9-39; Functional Dyspepsia Exendin 9-39; Healthy Controls Exendin 9-39

Microlipid DRUG

Lipid infusion {66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).

Diabetics Exendin 9-39; Diabetics Placebo; Functional Dyspepsia Exendin 9-39; Functional Dyspepsia Placebo; Healthy Controls Exendin 9-39; Healthy Controls Placebo

Placebo DRUG

Normal saline infusion will be prepared to match the appearance of Exendin 9-39

Diabetics Placebo; Functional Dyspepsia Placebo; Healthy Controls Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or non-pregnant, non-breastfeeding female volunteers;
• 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
• 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

You may not qualify if:

• 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
• 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 48 months

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Chakraborty S, Halland M, Burton D, Desai A, Neja B, Low P, Singer W, Camilleri M, Zinsmeister AR, Bharucha AE. GI Dysfunctions in Diabetic Gastroenteropathy, Their Relationships With Symptoms, and Effects of a GLP-1 Antagonist. J Clin Endocrinol Metab. 2019 Jun 1;104(6):1967-1977. doi: 10.1210/jc.2018-01623.

  PMID: 30358871 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Dyspepsia

Interventions

exendin (9-39); Safflower Oil

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Plant Preparations; Biological Products; Complex Mixtures; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Results Point of Contact

• Title: Dr. Adil E. Bharucha, Principal Investigator
• Organization: Mayo Clinic

bharucha.adil@mayo.edu

507-284-2687

Study Officials

• Adil Bharucha, MBBS, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 23, 2014
• Study Start: June 1, 2014
• Primary Completion: November 17, 2017
• Study Completion: November 17, 2017
• Last Updated: April 23, 2019
• Results First Posted: April 23, 2019

Record last verified: 2019-03

Locations

US (1)