Modulation of Esophageal Inflammation in Barrett's Esophagus by Omega-3 Fatty Acids

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01733147
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 2
• Duration (Months): 70.3
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This study is being done to understand the effect of dietary omega-3 fats in decreasing tissue inflammation in Barrett's esophagus.

Condition or Disease	Intervention/Treatment	Phase
Barrett's Esophagus; Obesity	Drug: Omega-3 polyunsaturated fatty acids; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Modulation of Esophageal Inflammation in Barrett's Esophagus by Omega-3 Fatty Acids, a Double Blind Placebo Controlled Randomized Pilot Study
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Sep 12, 2018
• Actual Study Completion Date: Sep 12, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive a placebo which looks exactly like the study drug, but contains no active ingredient, to be taken orally for six months.	Drug: Placebo; 3 capsules a day of placebo (1200 mg of ethyl oleate 3 capsules a day) taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal.
Active Comparator: Omega-3 polyunsaturated fatty acids Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive Omega-3 free fatty acids supplements to be taken orally for six months.	Drug: Omega-3 polyunsaturated fatty acids; 3 capsules a day of Omega 3 polyunsaturated fatty acids taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal. Active drug will consist of 1200 mg of a ω3 FFA preparation containing 675 mg EPA and 300 mg DHA.; Other Names: Docosahexaenoic Acid (DHA)/Eicosapentaenoic Acid (EPA)

Outcome Measures

Primary Outcome Measures

1. Change in Serum PGE2 Levels [Baseline, 6 months]

   Percent change from baseline to 6 months in serum prostaglandin E2 (PGE2) level obtained from blood draw

2. Change in Esophageal Tissue PGE2 Levels [Baseline, 6 months]

   Percent change from baseline to 6 months in esophageal tissue prostaglandin E2 (PGE2) level obtained from endoscopic esophageal tissue collection

Secondary Outcome Measures

1. Change in Esophageal Macrophage Markers [Baseline, 6 months]

   Percent change from baseline to 6 months in esophageal macrophage markers MCP-1 (Pro-inflammatory, M1 marker), CD 206 (Anti-inflammatory, M2 marker), and IL-10 (Anti-inflammatory, M2 marker) obtained from endoscopic esophageal tissue collection

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Presence of BE defined as ≥ 1 cm of visible columnar mucosa in the distal esophagus with intestinal metaplasia on histology.

• Absence of high grade dysplasia or EAC on baseline histology.

• BMI > 30 kg/m2 or waist circumference > 102 cm in men, > 88 cm in women.

• Ability to give informed consent.

Exclusion Criteria

• Allergy to ω3 FFAs, fish or shellfish.

• Presence of high grade dysplasia or cancer on histology.

• Pregnant and or breastfeeding women

• Presence of esophagitis on initial endoscopy or symptoms of refractory GERD (heartburn or regurgitation ≥ 2 times a week) indicative of uncontrolled gastroesophageal reflux.

• Inability to give informed consent.

• Currently taking Omega3 FFA as prescription.

• Anti-coagulant therapy (Plavix, Warfarin, Coumadin)

• AST or ALT level > three times upper limit of normal at baseline

• LDL > 200 mg/dl at baseline.

• INR > 2

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

Investigators

• Principal Investigator: Prasad Iyer, MD, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 25, 2018

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Prasad G. Iyer, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01733147
• Other Study ID Numbers: 12-005914
• First Posted: Nov 26, 2012
• Last Update Posted: Jan 11, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Prasad G. Iyer, Principal Investigator, Mayo Clinic: Omega-3 fatty acid
• Additional relevant MeSH terms: Barrett Esophagus; Esophagitis; Inflammation

Study Results

Participant Flow

Arm/Group Title	Placebo	Omega-3 Polyunsaturated Fatty Acids
Arm/Group Description	Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive a placebo which looks exactly like the study drug, but contains no active ingredient, to be taken orally for six months. Placebo: 3 capsules a day of placebo (1200 mg of ethyl oleate 3 capsules a day) taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal.	Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive Omega-3 free fatty acids supplements to be taken orally for six months. Omega-3 polyunsaturated fatty acids: 3 capsules a day of Omega 3 polyunsaturated fatty acids taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal. Active drug will consist of 1200 mg of a ω3 FFA preparation containing 675 mg EPA and 300 mg DHA.
Period Title: Overall Study
STARTED	30	30
COMPLETED	30	30
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Omega-3 Polyunsaturated Fatty Acids	Total
Arm/Group Description	Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive a placebo which looks exactly like the study drug, but contains no active ingredient, to be taken orally for six months. Placebo: 3 capsules a day of placebo (1200 mg of ethyl oleate 3 capsules a day) taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal.	Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive Omega-3 free fatty acids supplements to be taken orally for six months. Omega-3 polyunsaturated fatty acids: 3 capsules a day of Omega 3 polyunsaturated fatty acids taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal. Active drug will consist of 1200 mg of a ω3 FFA preparation containing 675 mg EPA and 300 mg DHA.	Total of all reporting groups
Overall Participants	30	30	60
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	66	66.5	66
Sex: Female, Male (Count of Participants)
Female	5 16.7%	11 36.7%	16 26.7%
Male	25 83.3%	19 63.3%	44 73.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	30 100%	30 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Change in Serum PGE2 Levels
Description	Percent change from baseline to 6 months in serum prostaglandin E2 (PGE2) level obtained from blood draw
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omega-3 Polyunsaturated Fatty Acids
Arm/Group Description	Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive a placebo which looks exactly like the study drug, but contains no active ingredient, to be taken orally for six months. Placebo: 3 capsules a day of placebo (1200 mg of ethyl oleate 3 capsules a day) taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal.	Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive Omega-3 free fatty acids supplements to be taken orally for six months. Omega-3 polyunsaturated fatty acids: 3 capsules a day of Omega 3 polyunsaturated fatty acids taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal. Active drug will consist of 1200 mg of a ω3 FFA preparation containing 675 mg EPA and 300 mg DHA.
Measure Participants	30	30
Median (Inter-Quartile Range) [Percentage of change in serum PGE2 level]	4.44	-21.65

2. Primary Outcome

Title	Change in Esophageal Tissue PGE2 Levels
Description	Percent change from baseline to 6 months in esophageal tissue prostaglandin E2 (PGE2) level obtained from endoscopic esophageal tissue collection
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omega-3 Polyunsaturated Fatty Acids
Arm/Group Description	Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive a placebo which looks exactly like the study drug, but contains no active ingredient, to be taken orally for six months. Placebo: 3 capsules a day of placebo (1200 mg of ethyl oleate 3 capsules a day) taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal.	Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive Omega-3 free fatty acids supplements to be taken orally for six months. Omega-3 polyunsaturated fatty acids: 3 capsules a day of Omega 3 polyunsaturated fatty acids taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal. Active drug will consist of 1200 mg of a ω3 FFA preparation containing 675 mg EPA and 300 mg DHA.
Measure Participants	30	30
Median (Inter-Quartile Range) [Percentage of change in esophageal PGE2]	0.82	11.87

3. Secondary Outcome

Title	Change in Esophageal Macrophage Markers
Description	Percent change from baseline to 6 months in esophageal macrophage markers MCP-1 (Pro-inflammatory, M1 marker), CD 206 (Anti-inflammatory, M2 marker), and IL-10 (Anti-inflammatory, M2 marker) obtained from endoscopic esophageal tissue collection
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omega-3 Polyunsaturated Fatty Acids
Arm/Group Description	Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive a placebo which looks exactly like the study drug, but contains no active ingredient, to be taken orally for six months. Placebo: 3 capsules a day of placebo (1200 mg of ethyl oleate 3 capsules a day) taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal.	Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive Omega-3 free fatty acids supplements to be taken orally for six months. Omega-3 polyunsaturated fatty acids: 3 capsules a day of Omega 3 polyunsaturated fatty acids taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal. Active drug will consist of 1200 mg of a ω3 FFA preparation containing 675 mg EPA and 300 mg DHA.
Measure Participants	30	30
MCP-1 (Pro-inflammatory, M1 marker)	4.81	2.12
CD 206 (Anti-inflammatory, M2 marker)	4.19	2.00
IL-10 (Anti-inflammatory M2 marker)	1.91	-0.53

Adverse Events

Time Frame	Adverse events were collected from baseline to end of study for a total of approximately 6 months on all participants.
Arm/Group Title	Placebo		Omega-3 Polyunsaturated Fatty Acids
Arm/Group Description	Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive a placebo which looks exactly like the study drug, but contains no active ingredient, to be taken orally for six months. Placebo: 3 capsules a day of placebo (1200 mg of ethyl oleate 3 capsules a day) taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal.		Subjects with known Barrett's Esophagus (no dysplasia and low-grade dysplasia) will receive Omega-3 free fatty acids supplements to be taken orally for six months. Omega-3 polyunsaturated fatty acids: 3 capsules a day of Omega 3 polyunsaturated fatty acids taken orally for six months; 2 capsules with breakfast and 1 capsule with their evening meal. Active drug will consist of 1200 mg of a ω3 FFA preparation containing 675 mg EPA and 300 mg DHA.
All Cause Mortality
	Placebo		Omega-3 Polyunsaturated Fatty Acids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Serious Adverse Events
	Placebo		Omega-3 Polyunsaturated Fatty Acids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Omega-3 Polyunsaturated Fatty Acids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		2/30 (6.7%)
Gastrointestinal disorders
Mild nausea	1/30 (3.3%)	1	0/30 (0%)	0
Diarrhea	0/30 (0%)	0	2/30 (6.7%)	2

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.