Efficacy of Omega-3 Fatty Acid Therapy in Preventing Gastrointestinal Bleeding in Patients With CF-LVAD

Open-Label Prospective Randomized Control Trial to Investigate the Efficacy of Omega-3 Fatty Acid Therapy in Preventing Gastrointestinal Bleeding in Patients With Continuous-Flow Left Ventricular Assist Device

This study evaluates the efficacy of high-dose fish oil in decreasing rates of gastrointestinal bleeding in patients with continuous-flow left ventricular assist devices. Half of the patients without history of bleeding will receive fish oil while the other half will not. Half of the patients with history of bleeding will receive fish oil while the other half will not. Markers of angiogenesis and inflammation, as well as changes in the microbiome will be assessed in each group.

Study Overview

• Status: Terminated
• Conditions: Heart Failure; Gastrointestinal Bleeding
• Intervention / Treatment: Drug: Omega 3 fatty acids; Other: Placebo

Detailed Description

A potential mechanism of bleeding in patients with continuous-flow left ventricular assist devices (CF-LVAD) is dysfunctional angiogenesis. Angiogenesis is a complicated process controlled by several markers. Previous studies have shown that elevated Angiopoietin-2 and TNF-alpha are associated with bleeding events in CF-LVAD patients.

Fish oil has anti-inflammatory and potentially anti-angiogenic properties. A retrospective study of CF-LVAD patients on high-dose fish oil showed a marked decrease in gastrointestinal bleeding rates in these patients. Additionally, these patients had lower levels of circulating Angiopoietin-2. Fish oil is known to have an effect on the microbiome, and the aforementioned effects may be seen in changes of the microbiota.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has signed consent
2. Age > 18 years
3. Subjects with a CF-LVAD or are scheduled to receive a CF-LVAD implant

Exclusion Criteria:

1. Psychiatric disorder or disease, irreversible cognitive dysfunction or psychosocial issues that might impair compliance with the study.
2. Patients already taking fish oil.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary Prevention Intervention; In patients with CF-LVAD who have not had a gastrointestinal bleed, patients randomized to intervention will receive 4 grams of Nature Made Ultra Omega-3 Fish Oil once daily for 1 year along with standard of care.	Drug: Omega 3 fatty acids; Patients will receive 4 grams fish oil once daily
Placebo Comparator: Primary Prevention Non-Intervention; In patients with CF-LVAD who have not had a gastrointestinal bleed, patients randomized to placebo will receive no fish oil and only standard of care.	Other: Placebo; Standard of care
Experimental: Secondary Prevention Intervention; In patients with CF-LVAD who have had a gastrointestinal bleed, patients randomized to intervention will receive 4 grams of Nature Made Ultra Omega-3 Fish Oil once daily for 1 year along with standard of care.	Drug: Omega 3 fatty acids; Patients will receive 4 grams fish oil once daily
Placebo Comparator: Secondary Prevention Non-Intervention; In patients with CF-LVAD who have had a gastrointestinal bleed, patients randomized to placebo will receive no fish oil and only standard of care.	Other: Placebo; Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Markers of Angiogenesis - Angiopoietin 1/2 and VEGF	Markers of angiogenesis and inflammation will be measured on customized Luminex assay panels. These will include Angiopoietin-1 (ng/mL), Angiopoietin-2 (ng/mL), and VEGF (ng/mL).	Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization.
Change in Markers of Angiogenesis - TNF-alpha	Markers of angiogenesis and inflammation will be measured on customized Luminex assay panels. These will include TNF-alpha (pg/mL).	Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization.
Change in Markers of Inflammation - C-Reactive Protein	Markers of angiogenesis and inflammation will be measured on customized Luminex assay panels. These will include c-reactive protein (mg/dL).	Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of Gastrointestinal Bleeding	Rates of Gastrointestinal Bleeding will be assessed.	Rates of bleeding will be measured at 3 months, 6 months, and 12 months after randomization.
Changes in the Microbiome	The microbiome will be assessed using rectal swabs. The swabs will be analyzed to determine the bacterial species present at each time point.	The microbiome will be assessed at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization.

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Ann Nguyen, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2019
• Primary Completion (Actual): July 15, 2020
• Study Completion (Actual): July 15, 2020

Study Registration Dates

• First Submitted: December 3, 2018
• First Submitted That Met QC Criteria: December 19, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Actual): July 13, 2021
• Last Update Submitted That Met QC Criteria: June 22, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Inflammation; Microbiome; Angiogenesis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Hemorrhage; Gastrointestinal Hemorrhage
• Other Study ID Numbers: IRB18-0576

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes