The Effects of Lipinova on Inflammatory and Proresolving Lipid Mediator Profiles After Orthopedic Surgery

February 13, 2018 updated by: Mieke A. Soens, Brigham and Women's Hospital

The Effects of Dietary Supplementation With Lipinova on Inflammatory and Proresolving Lipid Mediator Profiles in Patients Undergoing Total Knee Arthroplasty

The aim of this pilot study is to investigate whether pre-operative supplementation with an over the counter dietary supplement containing a fractionated marine lipid concentrate derived from anchovy and sardine oil, Lipinova® (Solutex), improves the inflammatory profile and proresolving capacity in patients undergoing total knee arthroplasty. In addition, the investigators will compare the ability of two different dosing regimens to maximize SPM (Specialized Proresolving Mediators) availability.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The resolution of acute inflammation was once thought to be a passive process, meaning that inflammatory mediators from the acute response (e.g. chemoattractants, complement components, prostaglandins, chemokines and cytokines) would simply dilute and dissipate to stop the infiltration of leucocytes into the tissues. Conversely, more recently it was shown that tissue resolution of inflammation is actually an active programmed process, requiring a temporal lipid mediator class switch that leads to the production of specialized pro-resolving mediators (SPMs) derived from essential fatty acids.1-4

There are several distinct classes of SPMs: the lipoxins derived from the n-6 polyunsaturated fatty acid (n-6 PUFA), AA, and the resolvins, protectins and maresins derived from the n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These SPMs counter regulate pro-inflammatory mediator production, including prostaglandins, leukotrienes, and select cytokines. They also stimulate leucocyte responses including bacterial phagocytosis and efferocytosis of apoptotic cells, key processes in the clearance of infections and return to homeostasis, without apparent immune suppression.5-7 In addition, Serhan and colleagues8 recently identified a new family of sulfido-conjugated mediators that promote wound repair and tissue regeneration. An increasing body of research has shown the beneficial actions of these mediators on improving the inflammatory process in several disease states, such as sepsis, peritonitis, colitis, Alzheimer's disease and peripheral vascular disease.9-13 In addition, it was demonstrated that RvE1 has direct bone-preserving and bone regeneration functions in a mouse model of periodontal disease.14

There is also increasing evidence suggesting that inflammation has a significant impact on postoperative clinical outcomes. Kimura et al.15 demonstrated that patients who developed postoperative infectious complications after liver resection had significantly higher levels of IL-6 on days 0 and 1 after surgery than did those without infections. In addition, elevated pre-operative CRP-levels in patients undergoing palliative surgery is associated with a higher complication rates and decreased overall survival.16 Pillai et al.17 demonstrated two groups among patients undergoing abdominal aorta aneurysm (AAA) surgery based on their temporal profile: one group displayed a pro-inflammatory profile throughout the intra-operative and postoperative time course, while the other group was characterized by a pro-resolving mediator profile. The authors suggested that these two broad categories may reflect an early resolver population and a delayed resolver population and that enhancing the patient profile of endogenous pro-resolving mediators may shorten recovery times, resolution and improve outcomes in these patients.

In this proposal the investigators aim to determine whether pre-operative dietary supplementation with a nutritional supplement containing omega-3 PUFA and its derivatives will improve the metabolo-lipidomic, inflammatory, and resolution profile of patients undergoing total knee arthroplasty. Lipinova® (Solutex) is an over the counter nutritional supplement that differs from other commercially available "Fish Oil" in that it contains standardized levels of the omega 3- PUFAs, Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) as well as the derived monohydroxylated precursors (17-HDHA, 18-HEPE and 14-HDHA). The standardized levels are obtained from anchovy and sardine oil through advanced fractionation technology and purification technology.

SPECIFIC AIMS:

Specific Aim 1: To characterize the pro-resolving lipid mediator (LM) or specialized pro-resolving mediator (SPM) signature in patients scheduled to undergo total knee arthroplasty. We hypothesize that orthopedic surgery will induce an up-regulation of pro-inflammatory pathways and down-regulation of pro-resolving lipid mediator pathways on postoperative day 1, when compared to pre-operatively.

Specific Aim 2: To determine if pre-operative dietary supplementation with Lipinova®, a purified, fractionated form of fish oil, containing standardized amounts of n-3 essential fatty acids, alters the metabolo-lipidomic profile in patients undergoing total knee arthroplasty. We hypothesize that the oral administration of Lipinova®, which contains precursors for SPMs will upregulate the pro-resolving lipid mediator pathways and down-regulate pro-inflammatory pathways in patients scheduled to undergo total knee arthroplasty, both pre-operatively and on postoperative day 1.

Specific Aim 3: To define a dosing regimen to maximize SPM availability in patients undergoing total knee arthroplasty surgery. We will compare changes in metabolo-lipidomic profiles between patients receiving 2 different doses of Lipinova® supplementation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients scheduled to undergo total knee arthroplasty at Brigham and Women's Hospital

Exclusion Criteria:

  • current treatment with corticosteroids or NSAIDs
  • evidence of active infection
  • chronic liver disease
  • end stage renal disease (CKD-5)
  • chronic inflammatory disorders
  • recent major illness or surgery within 30 days
  • use of immunosuppressive medication
  • history of organ transplantation
  • pregnancy or plans to become pregnant, or lactating
  • allergies to fish or fish oil
  • coagulation disorders or thrombocytopenia (platelet < 150,000)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Patients will be taking placebo twice daily for 5 days prior to surgery. The placebo has a similar taste and smell as the active supplement.
Dietary supplement: Placebo
Placebo will have a similar appearance, smell and taste as the nutritional supplement
Experimental: low dose Lipinova (30mL)
Patients will take 15 mL Lipinova (a dietary supplement containing omega-3 PUFA's) twice daily for 5 days prior to surgery.
Dietary supplement: low dose Lipinova (30 mL daily)
Lipinova is a nutritional supplement containing concentrated n-3 PUFA (EPA and DHA) and metabolites
Experimental: high dose Lipinova (60mL)
Patients will take 30mL of Lipinova (a dietary supplement containing omega-3 PUFA's) twice daily for 5 days prior to surgery.
Dietary supplement: high dose Lipinova (60mL)
Lipinova is a nutritional supplement containing concentrated n-3 PUFA (EPA and DHA) and metabolites

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
SPM signature profile/Resolution Index
Time Frame: 6 months
cumulative levels (in pg/mL) in plasma and serum for DHA-derived SPMs (D-series resolvins: RvD1, RvD2, RvD3, RvD4, RvD5, RvD6, 17R-RvD1 and 17R-RvD3), Protectins (PD1, 17R-PD1), Maresins (MaR1) + EPA-derived SPMs (E-series Resolvins (RvE1, RvE2 and RvE3) + n-3 DPA-derived SPM (RvD1 n-3 DPA, RvD2n-3 DPA and RvD5 n-3 DPA), Protectins (10S, 17S-diHDPA), Marins (MaR1 n-3 DPA) and AA-derived Lipoxins (LXA4, LXB4, 15-epi-LXA4 and 15-epi-LXB4). Cumulative levels (in pg/mL) will be compared before and after treatment with supplement/placebo and before and after surgery. Lipid mediator profiling will be done with LC-MSMS.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Brigham and Women's Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mieke Soens, MD, Brigham and Women's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 15, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 1, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 13, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 15, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 15, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 13, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2018P000102/PHS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Inflammation

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings