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

Adil Bharucha

Status and phase: Completed; Phase 1

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: Erythromycin Ethylsuccinate Suspension; Drug: Placebo Suspension; Drug: Placebo IV; Drug: [13C]-Spirulina; Drug: Erythromycin lactobionate

Study type: Interventional

Funder types: Other

Identifiers

NCT02755064

UL1TR000135 (U.S. NIH Grant/Contract)

08-008620

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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30 participants in 5 patient groups, including a placebo group

Erythromycin lactobionate IV 2 mg/kg

Experimental group

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.

Treatment:

Drug: Erythromycin lactobionate

Drug: [13C]-Spirulina

Erythromycin lactobionate IV 3 mg/kg

Active Comparator group

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.

Treatment:

Drug: Erythromycin lactobionate

Drug: [13C]-Spirulina

Placebo IV

Placebo Comparator group

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.

Treatment:

Drug: [13C]-Spirulina

Drug: Placebo IV

Erythromycin Ethylsuccinate Suspension

Experimental group

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.

Treatment:

Drug: [13C]-Spirulina

Drug: Erythromycin Ethylsuccinate Suspension

Placebo Suspension

Placebo Comparator group

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.

Treatment:

Drug: [13C]-Spirulina

Drug: Placebo Suspension