The Use of Icosapent Ethyl on Vascular Progenitor Cells in Individuals With Elevated Cardiovascular Risk

NCT04562467 | Completed Phase 4

• 1 other identifier: Pro00043561
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 3

Brief Summary

IPE-PREVENTION is a prospective, randomized, 3-month long, open-label study. A total of 70 individuals with elevated cardio-metabolic risk and heightened triglyceride levels, and who are on stable statin therapy will be randomized (1:1) to receive either icosapent ethyl (IPE) 2g BID or standard of care. It is hypothesized that assignment to IPE will lower progenitor cell depletion as well as limit progenitor cell dysfunction. This study may offer some molecular and cellular insights into the mechanisms underlying the cardiovascular benefits of IPE therapy reported in the REDUCE-IT trial.

Conditions

Cardiovascular Diseases; Cardiovascular Risk Factor; Triglycerides High; Diabetes Mellitus, Type 2

Keywords

Cardiometabolic Risk; Type 2 Diabetes; Icosapent Ethyl; Omega-3; Vascular Diseases; Progenitor Cells; Vascular Disease; Blood Lipids

Outcome Measures

Primary Outcomes (1)

• Change in the frequency of ALDHhiSSClowCD133+ cells in individuals treated with IPE compared to SOC for 3 months

  Baseline - 3 months post-randomization

Other Outcomes (4)

• Change in the ratio of ALDHhiSSCmid pro-inflammatory:anti-inflammatory monocyte precursor cells in individuals treated with IPE compared to SOC for 3-months.

  Baseline - 3 months post-randomization

• Change in the mean frequency of ALDHhiSSChi cells in individuals treated with IPE compared to SOC for 3-months.

  Baseline - 3 months post-randomization

• Changes in the concentration of serum oxidative stress markers from baseline to the 3-month visit in individuals treated with IPE compared to SOC

  Baseline - 3 months post-randomization

Study Arms (2)

Icosapent Ethyl + Standard of Care

EXPERIMENTAL

Icosapent Ethyl 1000 MG Oral Capsule \[Vascepa\] 2 x 1g capsules BID (4g total) as per REDUCE-IT

Drug: Icosapent Ethyl 1000 MG Oral Capsule [Vascepa]

Standard of Care

NO INTERVENTION

Standard of care therapy (including statin therapy as per inclusion criteria)

Interventions

Icosapent Ethyl 1000 MG Oral Capsule [Vascepa] DRUG

2 x 1g capsules BID as per REDUCE-IT

Also known as: Vascepa, IPE

Icosapent Ethyl + Standard of Care

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women ≥65 years of age and men ≥40 years of age with established CVD (see criterion 'a' below) or ≥50 years of age with diabetes and one additional CV risk factor (see criterion 'b' below)
• Those with established CVD should have ≥1 of the following clinical history
• Documented coronary artery disease (CAD)
• Prior MI
• Multivessel CAD (≥50% stenosis in ≥2 major epicardial coronary arteries)
• Hospitalization for high-risk non-ST-segment elevation acute coronary syndrome
• Documented cerebrovascular or carotid disease (≥1 of the following)
• Prior ischemic stroke
• Carotid artery disease with ≥50% stenosis
• History of carotid revascularization
• Documented peripheral artery disease (≥1 of the following)
• Ankle-brachial index (ABI) \<0.9 with symptoms of intermittent claudication
• History of aorto-iliac or peripheral arterial intervention
• Those with a history of diabetes (either type 1 or type 2 diabetes mellitus) but no CVD should also have ≥1 of the following:
• Cigarette smoker or stopped smoking within 3 months before the baseline visit

You may not qualify if:

• Participation in another clinical trial with an investigational agent ≤90 days prior to screening
• Women who are of childbearing potential
• Any condition or therapy which the study doctor thinks might pose a risk to the participant
• Severe (New York Heart Association class IV) heart failure
• Any life-threatening disease expected to result in death within the next 2 years
• Diagnosis or laboratory evidence of active severe liver disease
• HbA1c \>10.0% at the baseline visit
• SBP ≥200 mmHg or DBP ≥100 mmHg (despite being on antihypertensive therapy)
• Planned coronary intervention or any non-cardiac major surgical procedure
• Known familial lipoprotein lipase deficiency, apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia
• Statin intolerant or hypersensitivity to statin therapy
• Require peritoneal dialysis or hemodialysis
• eGFR \<30 mL/min/1.73m2
• History of atrial fibrillation
• History of major bleeding event(s)

Sponsors & Collaborators

• Canadian Medical and Surgical Knowledge Translation Research Group: lead
• HLS Therapeutics, Inc: collaborator
• Unity Health Toronto: collaborator
• Western University, Canada: collaborator

Study Sites (3)

The Oshawa Clinic

Oshawa, Ontario, L1H 1B9, Canada

Location

Diagnostic Assessment Centre

Scarborough Village, Ontario, M1S4N6, Canada

Location

Langstaff Medical Clinic

Vaughan, Ontario, L4L 0K8, Canada

Location

Related Publications (16)

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• Bakbak E, Krishnaraj A, Bhatt DL, Quan A, Park B, Bakbak AI, Bari B, Terenzi KA, Pan Y, Fry EJ, Terenzi DC, Puar P, Khan TS, Rotstein OD, Mazer CD, Leiter LA, Teoh H, Hess DA, Verma S. Icosapent ethyl modulates circulating vascular regenerative cell content: The IPE-PREVENTION CardioLink-14 trial. Med. 2024 Jul 12;5(7):718-734.e4. doi: 10.1016/j.medj.2024.03.009. Epub 2024 Mar 28.

  PMID: 38552629 RESULT

MeSH Terms

Conditions

Cardiovascular Diseases; Hypertriglyceridemia; Diabetes Mellitus, Type 2; Vascular Diseases

Interventions

eicosapentaenoic acid ethyl ester

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Endocrine System Diseases

Study Officials

• Subodh Verma, MD, PhD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

• David A Hess, PhD

  Robarts Research Institute, London, Ontario

  PRINCIPAL INVESTIGATOR

• Deepak L Bhatt, MD, MPH

  Brigham and Women's Hospital, Boston, Massachusetts

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2020
• First Posted: September 24, 2020
• Study Start: September 24, 2020
• Primary Completion: May 25, 2023
• Study Completion: May 25, 2023
• Last Updated: April 2, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)