Back to resultsRelationship Between Gastric Emptying and Glycemic Variability in Type 1 Diabetes Mellitus
Primary Purpose
Diabetes Mellitus, Type 1
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Erythromycin lactobionate
Placebo IV
[13C]-Spirulina
Erythromycin Ethylsuccinate Suspension
Placebo Suspension
Sponsored by
About this trial
This is an interventional basic science trial for Diabetes Mellitus, Type 1
Eligibility Criteria
Inclusion Criteria:
- 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 %
Exclusion Criteria:
- 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.
Sites / Locations
- Mayo Clinic
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Active Comparator
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Erythromycin lactobionate IV 2 mg/kg
Erythromycin lactobionate IV 3 mg/kg
Placebo IV
Erythromycin Ethylsuccinate Suspension
Placebo Suspension
Arm Description
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
Relationship between gastric emptying and glycemia
GE was measured by 13C spirulina GEBT. Glycemia was measured with continuous glucose monitoring.
Secondary Outcome Measures
Number of subjects with delayed gastric emptying
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02755064
Brief Title
Relationship Between Gastric Emptying and Glycemic Variability in Type 1 Diabetes Mellitus
Official Title
Relationship Between Gastric Emptying and Glycemic Variability in Type 1 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Adil Bharucha
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
Detailed Description
The study comprised 3 outpatient visits over a period of 11 days. Safety lab test were performed at the screening visit. At each visit, GE was evaluated by 13C-spirulina breath tests.
Phase 1:
After the baseline assessment (GE1), the second and third GE tests were performed during treatment with intravenous (GE2) and oral erythromycin (GE3) or placebo. Subject arrived fasting at each study visit. Prior to gastric emptying study, there was placement of an intravenous line. Subject continued to take insulin and other medications as usual. Subjects were required to do finger-stick glucose readings 4 times a day or as instructed by their physician. Subjects were provided with a log sheet to keep track of meal times, insulin dosing and times, glucose readings, and activities. Continuous glucose monitoring (CGM) and gastric emptying were evaluated for the duration of the study (11 days) and thrice respectively. GE was evaluated at baseline (GE1) and after randomized to intravenous saline, erythromycin (2 mg/kg) or erythromycin (3 mg/kg).
Phase 2:
Thereafter, patients were randomized to erythromycin ethyl succinate suspension (250 mg tid) or placebo for a total period of 7 days. GE3 was preferably performed on day 7, after oral erythromycin or placebo was started.
An EKG was performed at baseline to identify (and exclude) patients who have contraindications to erythromycin. An EKG was also repeated at the end of the study, i.e., on GE3 for safety. No change to insulin (apart from those that patients do with their self management skills) or other medications was made during this research study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Erythromycin lactobionate IV 2 mg/kg
Arm Type
Experimental
Arm Description
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.
Arm Title
Erythromycin lactobionate IV 3 mg/kg
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo IV
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Erythromycin Ethylsuccinate Suspension
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo Suspension
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Erythromycin lactobionate
Other Intervention Name(s)
Erythrocin™ Lactobionate-IV
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo IV
Other Intervention Name(s)
Saline
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
[13C]-Spirulina
Other Intervention Name(s)
Carbon-13 Spirulina Breath Test, Gastric Emptying Breath Test (GEBT)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Erythromycin Ethylsuccinate Suspension
Other Intervention Name(s)
E.E.S.
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo Suspension
Intervention Description
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.
Primary Outcome Measure Information:
Title
Relationship between gastric emptying and glycemia
Description
GE was measured by 13C spirulina GEBT. Glycemia was measured with continuous glucose monitoring.
Time Frame
11 days
Secondary Outcome Measure Information:
Title
Number of subjects with delayed gastric emptying
Time Frame
11 days
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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 %
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adil E Bharucha, MBBS, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
27880079
Citation
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.
Results Reference
derived
Learn more about this trial
Relationship Between Gastric Emptying and Glycemic Variability in Type 1 Diabetes Mellitus
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