Relationship Between Gastric Emptying and Glycemic Variability in Type 1 Diabetes Mellitus

NCT02755064 | Completed Phase 1

• 2 other identifiers: 08-008620UL1TR000135
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

With this study, the investigators hoped to learn if the rate at which food empties from the stomach affects blood sugar values. Using data from this study, we hope to improve our ability to control blood sugars in individuals with type 1 diabetes mellitus.

Conditions

Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (1)

• Relationship between gastric emptying and glycemia

  GE was measured by 13C spirulina GEBT. Glycemia was measured with continuous glucose monitoring.

  11 days

Secondary Outcomes (1)

• Number of subjects with delayed gastric emptying

  11 days

Study Arms (5)

Erythromycin lactobionate IV 2 mg/kg

EXPERIMENTAL

During the second visit, erythromycin was given as an initial bolus of 0.5 mg/kg over 10 min immediately before the meal. The subject consumed the test meal containing 13C-Spirulina in no more than 10 minutes. Breath samples were collected at baseline obtained upon completion of the meal and at 15, 30, 45, 60, 90, 120, 150, 180, and 240 minute time points. Thereafter, an infusion of 1.5 mg/kg was given over the next 50 min with the same infusion pump.

Drug: Erythromycin lactobionate; Drug: [13C]-Spirulina

Erythromycin lactobionate IV 3 mg/kg

ACTIVE COMPARATOR

During the second visit, erythromycin was given as an initial bolus of 0.5 mg/kg over 10 min immediately before the meal. The subject consumed the test meal containing 13C-Spirulina in no more than 10 minutes. Breath samples were collected at baseline obtained upon completion of the meal and at 15, 30, 45, 60, 90, 120, 150, 180, and 240 minute time points.Thereafter, an infusion of 1.5 mg/kg was given over the next 50 min with the same infusion pump.

Drug: Erythromycin lactobionate; Drug: [13C]-Spirulina

Placebo IV

PLACEBO COMPARATOR

Saline was given as an initial bolus over 10 min immediately before the meal. The subject consumed the test meal containing 13C-Spirulina in no more than 10 minutes. Breath samples were collected at baseline obtained upon completion of the meal and at 15, 30, 45, 60, 90, 120, 150, 180, and 240 minute time points. Thereafter, an infusion of saline was given over the next 50 min with the same infusion pump.

Drug: Placebo IV; Drug: [13C]-Spirulina

Erythromycin Ethylsuccinate Suspension

EXPERIMENTAL

In Phase 2 of the study, subjects randomized to this arm will receive Erythromycin Ethylsuccinate Suspension 250 mg tid orally for a total period of 7 days. The GEBT was performed approximately on day 7. The subject consumed the test meal containing 13C-Spirulina in no more than 10 minutes. Breath samples were collected at baseline obtained upon completion of the meal and at 15, 30, 45, 60, 90, 120, 150, 180, and 240 minute time points.

Drug: [13C]-Spirulina; Drug: Erythromycin Ethylsuccinate Suspension

Placebo Suspension

PLACEBO COMPARATOR

In Phase 2 of the study, subjects randomized to this arm will receive an oral placebo prepared to mimic the Erythromycin Ethylsuccinate Suspension for a total period of 7 days. The GEBT was performed approximately on day 7. The subject consumed the test meal containing 13C-Spirulina in no more than 10 minutes. Breath samples were collected at baseline obtained upon completion of the meal and at 15, 30, 45, 60, 90, 120, 150, 180, and 240 minute time points.

Drug: [13C]-Spirulina; Drug: Placebo Suspension

Interventions

Erythromycin lactobionate DRUG

In Phase 1 of the study, during the second visit, erythromycin was given as an initial bolus of 0.5 mg/kg over 10 min immediately before the meal. Thereafter, an infusion of 1.5 or 2.5 mg/kg was given over the next 50 min with the same infusion pump. The goal of testing 2 different doses was not to assess dose-related effects but to compare glycemic indices against a spectrum of gastric emptying rates.

Also known as: Erythrocin™ Lactobionate-IV

Erythromycin lactobionate IV 2 mg/kg; Erythromycin lactobionate IV 3 mg/kg

Placebo IV DRUG

In Phase 1 of the study, during the second visit, saline was given as an initial bolus over 10 min immediately before the meal. Thereafter, an infusion of saline was given over the next 50 min with the same infusion pump.

Also known as: Saline

Placebo IV

[13C]-Spirulina DRUG

The subject consumed the test meal containing 13C-Spirulina in no more than 10 minutes. Breath samples were collected at baseline obtained upon completion of the meal and at 15, 30, 45, 60, 90, 120, 150, 180, and 240 minute time points.

Also known as: Carbon-13 Spirulina Breath Test, Gastric Emptying Breath Test (GEBT)

Erythromycin Ethylsuccinate Suspension; Erythromycin lactobionate IV 2 mg/kg; Erythromycin lactobionate IV 3 mg/kg; Placebo IV; Placebo Suspension

Erythromycin Ethylsuccinate Suspension DRUG

In Phase 2 of the study, subjects randomized to this arm will receive Erythromycin Ethylsuccinate Suspension 250 mg tid orally for a total period of 7 days.

Also known as: E.E.S.

Erythromycin Ethylsuccinate Suspension

Placebo Suspension DRUG

In Phase 2 of the study, subjects randomized to this arm will receive an oral placebo prepared to mimic the Erythromycin Ethylsuccinate Suspension for a total period of 7 days.

Placebo Suspension

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or non-pregnant non-breastfeeding female volunteers with type 1 diabetes mellitus (T1 DM) undergoing a clinically-indicated continuous glucose monitoring (CGM) study (Women of childbearing potential may be enrolled if they use contraceptives throughout the length of the study).
• 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.
• Glycated hemoglobin (A1c) \< 8.5 %

You may not qualify if:

• Severe nausea or vomiting precluding study assessments
• Use of medications that alter GI motility e.g., narcotics, medications with significant anticholinergic effects, CYP-450 3A4 inhibitors, antibiotics (other than the experimental drug erythromycin), pramlintide or GLP-1 based therapy. Subjects using metoclopramide or erythromycin will be enrolled but these medications will be held for 7 days before CGM1 and GE1
• Pancreas transplantation
• Contraindications to erythromycin: i.e., 1) concomitant therapy with astemizole, cisapride, pimozide, or terfenadine; 2) hypersensitivity to erythromycin or any component of the product; Corrected QT interval on EKG \>460 msec
• Known family history of sudden death or congenital QT prolongation
• Serum potassium and magnesium levels outside of normal range at screening or visit 1
• Patients with moderate or severe renal insufficiency, i.e., subjects with an eGFR \< 60 mL/min/1.73 m\^2)
• Patients who are allergic to eggs, wheat or milk or unwilling to consume these products.

Sponsors & Collaborators

• Adil Bharucha: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Parthasarathy G, Kudva YC, Low PA, Camilleri M, Basu A, Bharucha AE. Relationship Between Gastric Emptying and Diurnal Glycemic Control in Type 1 Diabetes Mellitus: A Randomized Trial. J Clin Endocrinol Metab. 2017 Feb 1;102(2):398-406. doi: 10.1210/jc.2016-2809.

  PMID: 27880079 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

erythromycin lactobionate; Sodium Chloride; Erythromycin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Adil E Bharucha, MBBS, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant, Professor of Medicine

Study Record Dates

• First Submitted: April 22, 2016
• First Posted: April 28, 2016
• Study Start: June 1, 2010
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: April 28, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)