Using Magnetic Resonance (MR) to Understand the Effect of Erythromycin on Bowel Motility

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01379183
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 4.4

Study Details

Study Description

Brief Summary

Magnetic Resonance Imaging (MRI) has proven to be a valuable imaging technique for suspected small bowel disease. This technique depends, in part, on adequate distension of the small bowel. This is accomplished by administering large volumes of a non-absorbable oral contrast material prior to the examination, which typically produces excellent distension of the distal small bowel and stomach, but poor distension of the proximal small bowel. Erythromycin is a common antibiotic that is known to promote stomach emptying and is used to treat diabetics with gastroparesis (poor stomach emptying.) The hypothesis of this study was that erythromycin will increase gastric emptying and hence improve small and large intestinal distention during MRI.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Erythromycin; Drug: Placebo; Procedure: Magnetic Resonance Imaging; Other: Barium Sulfate Solution	Phase 2/Phase 3

Detailed Description

Gastric, small, and large intestinal volumes were assessed with MRI after ingestion of a low concentration of barium sulfate solution (1350 mL) and randomization to erythromycin 200 mg i.v.) or placebo in 40 healthy volunteers. Magnetic Resonance Images of the abdomen were acquired with a torso phased array coil and a 1.5 tesla magnet.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Magnetic Resonance (MR) Evaluation of the Effect of Erythromycin Upon Gastric and Small Bowel Motility
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Erythromycin Erythromycin 200 mg i.v. suspension, Barium Sulfate Solution, and Magnetic Resonance Imaging	Drug: Erythromycin; 200 mg suspension; Other Names: Erythromycin suspension ; Procedure: Magnetic Resonance Imaging; An MR enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel.; Other Names: MRI Magnetic Resonance Enterography ; Other: Barium Sulfate Solution; Participants will be given a low concentration of barium sulfate solution (1350 mL) prior to the MRI procedure. Barium sulfate is a radiopaque agent. Radiopaque agents are used to help diagnose certain medical problems. Since radiopaque agents are opaque to (block) x-rays, the areas of the body in which they are localized will appear white on the x-ray film. This creates the needed distinction, or contrast, between one organ and other tissues. The contrast will help the doctor see any special conditions that may exist in that organ or part of the body.; Other Names: VoLumen
Placebo Comparator: Placebo Matching placebo i.v. suspension, Barium Sulfate Solution, and Magnetic Resonance Imaging	Drug: Placebo; 200 mg suspension; Other Names: Water in 0.9% Sodium Chloride ; Procedure: Magnetic Resonance Imaging; An MR enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel.; Other Names: MRI Magnetic Resonance Enterography ; Other: Barium Sulfate Solution; Participants will be given a low concentration of barium sulfate solution (1350 mL) prior to the MRI procedure. Barium sulfate is a radiopaque agent. Radiopaque agents are used to help diagnose certain medical problems. Since radiopaque agents are opaque to (block) x-rays, the areas of the body in which they are localized will appear white on the x-ray film. This creates the needed distinction, or contrast, between one organ and other tissues. The contrast will help the doctor see any special conditions that may exist in that organ or part of the body.; Other Names: VoLumen

Outcome Measures

Primary Outcome Measures

1. Gastric Volume [Approximately 60 minutes after beginning ingestion of fluid volume]

   A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. MR images of the abdomen were acquired with a torso phased array coil and a 1.5 tesla magnet MRI. Gastric volumes were assessed with an axial 3D axial gradient echo sequence, which imaged the entire stomach in 13 seconds.

Secondary Outcome Measures

1. Jejunal Volume [Approximately 60 minutes after beginning ingestion of fluid volume]

   The jejunum is the section of the small intestine between the duodenum and the ileum. A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. Small bowel volumes were evaluated with 5 mm thick coronal slices using a fat-suppressed true fast imaging with steady state precession sequence while the participant held his or her breath.

2. Ileal Volume [Approximately 60 minutes after beginning ingestion of fluid volume]

   The Ileal is the terminal portion of the small intestine extending from the jejunum to the cecum. A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. Small bowel volumes were evaluated with 5 mm thick coronal slices using a fat-suppressed true fast imaging with steady state precession sequence while the participant held his or her breath.

3. Colonic Volume [Approximately 60 minutes after beginning ingestion of fluid volume]

   A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. Small bowel volumes were evaluated with 5 mm thick coronal slices using a fat-suppressed true fast imaging with steady state precession sequence while the participant held his or her breath.

4. Small Intestine Volume [Approximately 60 minutes after beginning ingestion of fluid volume]

   A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. Small bowel volumes were evaluated with 5 mm thick coronal slices using a fat-suppressed true fast imaging with steady state precession sequence while the participant held his or her breath.

5. Small Intestine and Colon Volume [Approximately 60 minutes after beginning ingestion of fluid volume]

   A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. Small bowel volumes were evaluated with 5 mm thick coronal slices using a fat-suppressed true fast imaging with steady state precession sequence while the participant held his or her breath.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Normal healthy adult volunteers without known gastrointestinal disease

• Aged 18-70 years

• 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.

Exclusion Criteria:

• Known allergy to erythromycin;

• Use of drugs that have known contraindication with erythromycin (concomitant therapy with astemizole, cisapride, pimozide, or terfenadine)

• Corrected QT interval on EKG >460 msec

• Certain medications (i.e., theophylline, digoxin, oral anti-coagulant, benzodiazepine, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors) will either be excluded from the study or, if medically safe, will be asked to discontinue the medication for 4 half-lives before beginning the study.

• Use of medications that alter GI motility e.g., narcotics, medications with significant anticholinergic effects

• Pregnant or breast-feeding females

• Known claustrophobia

• Known family history of sudden death or congenital QT prolongation

• Presence of pacemaker, internal defibrillator, or other non-MR compatible device

• Patients with known metal present within their abdomen

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Jeff Fidler, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeff Fidler, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01379183
• Other Study ID Numbers: 10-004869; P01DK068055
• First Posted: Jun 23, 2011
• Last Update Posted: Mar 21, 2016
• Last Verified: Feb 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Jeff Fidler, Principal Investigator, Mayo Clinic: Healthy; Men; Women; No known gastrointestinal disease; Aged between 18-70 years
• Additional relevant MeSH terms: Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Erythromycin stearate

Study Results

Participant Flow

Recruitment Details	Recruitment period: 07/09/2011 - 03/13/2013 Location: Mayo Clinic, Rochester, Minnesota
Pre-assignment Detail	There was no wash out or run-in period following participant enrollment.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Erythromycin 200 mg i.v. suspension	Matching placebo i.v. suspension
Period Title: Overall Study
STARTED	19	21
COMPLETED	19	21
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Erythromycin	Placebo	Total
Arm/Group Description	Erythromycin 200 mg i.v. suspension	Matching placebo i.v. suspension	Total of all reporting groups
Overall Participants	19	21	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34 (12.6)	35 (13)	35 (13)
Sex: Female, Male (Count of Participants)
Female	12 63.2%	12 57.1%	24 60%
Male	7 36.8%	9 42.9%	16 40%
Region of Enrollment (participants) [Number]
United States	19 100%	21 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	Gastric Volume
Description	A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. MR images of the abdomen were acquired with a torso phased array coil and a 1.5 tesla magnet MRI. Gastric volumes were assessed with an axial 3D axial gradient echo sequence, which imaged the entire stomach in 13 seconds.
Time Frame	Approximately 60 minutes after beginning ingestion of fluid volume

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Erythromycin 200 mg i.v. suspension	Matching placebo i.v. suspension
Measure Participants	19	21
Mean (Standard Error) [mL]	262 (52)	718 (59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Jejunal Volume
Description	The jejunum is the section of the small intestine between the duodenum and the ileum. A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. Small bowel volumes were evaluated with 5 mm thick coronal slices using a fat-suppressed true fast imaging with steady state precession sequence while the participant held his or her breath.
Time Frame	Approximately 60 minutes after beginning ingestion of fluid volume

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Erythromycin 200 mg i.v. suspension Erythromycin: 200 mg suspension	Matching placebo i.v. suspension Placebo: 200 mg suspension
Measure Participants	19	21
Mean (Standard Error) [mL]	450 (74)	359 (43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Ileal Volume
Description	The Ileal is the terminal portion of the small intestine extending from the jejunum to the cecum. A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. Small bowel volumes were evaluated with 5 mm thick coronal slices using a fat-suppressed true fast imaging with steady state precession sequence while the participant held his or her breath.
Time Frame	Approximately 60 minutes after beginning ingestion of fluid volume

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Erythromycin 200 mg i.v. suspension Erythromycin: 200 mg suspension	Matching placebo i.v. suspension Placebo: 200 mg suspension
Measure Participants	19	21
Mean (Standard Error) [mL]	248 (30)	248 (27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Colonic Volume
Description	A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. Small bowel volumes were evaluated with 5 mm thick coronal slices using a fat-suppressed true fast imaging with steady state precession sequence while the participant held his or her breath.
Time Frame	Approximately 60 minutes after beginning ingestion of fluid volume

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Erythromycin 200 mg i.v. suspension Erythromycin: 200 mg suspension	Matching placebo i.v. suspension Placebo: 200 mg suspension
Measure Participants	19	21
Mean (Standard Error) [mL]	190 (53)	180 (36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Small Intestine Volume
Description	A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. Small bowel volumes were evaluated with 5 mm thick coronal slices using a fat-suppressed true fast imaging with steady state precession sequence while the participant held his or her breath.
Time Frame	Approximately 60 minutes after beginning ingestion of fluid volume

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Erythromycin 200 mg i.v. suspension Erythromycin: 200 mg suspension	Matching placebo i.v. suspension Placebo: 200 mg suspension
Measure Participants	19	21
Mean (Standard Error) [mL]	698 (99)	607 (56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Small Intestine and Colon Volume
Description	A Magnetic Resonance (MR) enterography procedure uses magnetic resonance imaging (MRI) technology to obtain detailed images of the small bowel. Small bowel volumes were evaluated with 5 mm thick coronal slices using a fat-suppressed true fast imaging with steady state precession sequence while the participant held his or her breath.
Time Frame	Approximately 60 minutes after beginning ingestion of fluid volume

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Erythromycin 200 mg i.v. suspension Erythromycin: 200 mg suspension	Matching placebo i.v. suspension Placebo: 200 mg suspension
Measure Participants	19	21
Mean (Standard Error) [mL]	910 (66)	781 (65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Arm/Group Title	Erythromycin		Placebo
Arm/Group Description	Erythromycin 200 mg i.v. suspension		Matching placebo i.v. suspension
All Cause Mortality
	Erythromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Erythromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Erythromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.