Early Aortic Valve Lipoprotein(a) Lowering Trial (EAVaLL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02109614
Recruitment Status : Recruiting
First Posted : April 10, 2014
Last Update Posted : September 13, 2016
Jewish General Hospital
Laval University
Quebec Heart Institute
Information provided by (Responsible Party):
George Thanassoulis, McGill University Health Center

Brief Summary:

Aortic valve disease is the most common form of heart valve disease and is a major burden to society. Aortic valve disease is also expected to become more prevalent with the aging of the Canadian population. Currently, over 1 million individuals in North America have aortic stenosis, which is a narrowing of the aortic valve, and leads to symptoms of heart failure and sometimes death. Valve replacement with its potential costs and complications remains the only avenue for treatment, once symptoms develop. Despite the major importance of this disease, there are currently no medical treatments to prevent the development of aortic stenosis.The lack of preventative treatments stems in large part to a poor understanding of the causes of this disease.

Using cutting-edge genetic technologies, the investigators have recently identified that individuals with a genetic predisposition to elevations in a type of cholesterol not normally screened, called lipoprotein(a), have a much higher risk of developing aortic valve disease. The investigators have also shown that lipoprotein(a) causes hardening of the valve, a very early sign of valve narrowing. The investigators plan to evaluate in a randomized controlled trial whether lowering this unusual form of cholesterol at an early stage of this disease could slow or stop the development of aortic valve narrowing

The investigators are currently proposing a pilot project to evaluate the feasibility of this type of study. If successful, our proposed treatment would be notable in two ways. First, it would represent the first medical treatment to prevent valve disease, which could lead to major reductions in the societal burden of this important disease. And second, it would herald a major success for genomic medicine as it would represent one of the first treatments borne from recent genetic studies. In these ways, our proposal could significantly impact the health of many Canadians while also highlighting the innovative research performed in Canada.

Recruitment (n=238) for this project will be from the echocardiography laboratories of McGill University affiliated hospitals. Individuals with aortic sclerosis or mild aortic stenosis (aortic valve area [AVA] >1.5 cm2, mean gradient [MG] < 25 mmHG) and high Lp(a) will be eligible for inclusion into this proposed study.

Condition or disease Intervention/treatment Phase
Aortic Stenosis and Lipoprotein(a) Levels Drug: Extended release Niacin Drug: Placebo Comparator Early Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 238 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Pilot,Randomized Controlled-trial of Lipoprotein(a) Lowering for the Prevention of Aortic Valve Disease-translating Genomic Knowledge for Cardiovascular Prevention
Study Start Date : May 2014
Estimated Primary Completion Date : January 2017
Estimated Study Completion Date : September 2017

Arm Intervention/treatment
Experimental: Extended release Niacin
Taking 1500-2000mg niacin daily
Drug: Extended release Niacin
Arm will be taking 1500-2000mg of niacin daily to see if lipoprotein(a) levels are lowered and aortic stenosis does not increase.

Placebo Comparator: No Naicin
Placebo Comparator arm will be taking 1500mg of placebo daily
Drug: Placebo Comparator
Placebo Comparator arm will be taking 1500mg of the placebo daily

Primary Outcome Measures :
  1. Calcium score progression by cardiac CT in individuals randomized to niacin as compared to those randomized to placebo [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Mean change in Lp(a) levels between treatment arms [ Time Frame: 2 years ]

Other Outcome Measures:
  1. Rates of valve disease progression by echocardiography at 1 and 2 years [ Time Frame: 1 and 2 years ]
    Change in peak velocity (in m/s); Change in mean gradient (in mm Hg); Change in AV area (in cm2)

  2. Drug compliance [ Time Frame: At 6, 12, 18 and 24 months ]
    Pill count and drug diary

  3. Side effects and adverse events [ Time Frame: at 6, 12, 18 and 24 months ]
    all common and rare serious side-effects/adverse events will be monitored

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age >50 years and < 85 years
  2. Aortic sclerosis OR mild AS

    • Aortic sclerosis: diffuse of focal (at least 2 areas) thickening or calcification (highly echodense lesions) on aortic leaflets seen in at least 2 contiguous views with normal leaflet excursion and peak aortic jet velocity < 2 m/s.
    • Mild AS: peak aortic jet velocity 2-3 cm/s, AVA >1.5cm2, mean gradient <25 m

      • Elevated Lp(a) > 50 mg/dL (>80th percentile).

Exclusion Criteria:

  1. Current use or documented indication for niacin therapy or known niacin allergy/intolerance
  2. Bicuspid valve, unicuspid valve or other congenital cardiac anomaly (except patent foramen ovale)
  3. Known renal disease or more than mild renal dysfunction (Creatinine > 150 mmol/L or Creatinine clearance < 60).
  4. Major comorbidities limiting life expectancy to < 2 years
  5. Unable or unwilling to complete follow-up visits to 2 year
  6. Diagnosed hepatic failure, cirrhosis, hepatitis or history of hepatic impairment (AST or ALT levels ³ 2 times upper limit of normal)
  7. Newly diagnosed (< 2 months) or poorly controlled diabetes
  8. Gout or use of anti-hyperuricemic medications

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02109614

Contact: Kimberley V Kotar, B.Sc 514-934-1934 ext 35661
Contact: George Thanassoulis, MD 514-934-1934

Canada, Quebec
MUHC - Montreal General Hospital Recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: Kimberley V Kotar, BSc    5149341934 ext 35661   
Principal Investigator: George Thanassoulis, MD MSc FRCPC         
MUHC - Royal Victoria Hospital Recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: Kimberley V Kotar, B.Sc    514934-1934 ext 35166   
Contact: George Thanassoulis, MD    514-934-1934 ext 35465   
Principal Investigator: George Thanassoulis, MD         
Jewish General Hospital Not yet recruiting
Montreal, Quebec, Canada, H3T 1E2
Contact: Kimberley V Kotar, B.Sc    514-934-1934 ext 35661   
Contact: Mark Eisenberg, MD    514-340-8222   
Principal Investigator: Mark Eisenberg, md         
Sponsors and Collaborators
George Thanassoulis
Jewish General Hospital
Laval University
Quebec Heart Institute

Responsible Party: George Thanassoulis, MD MSc FRCPC, McGill University Health Center Identifier: NCT02109614     History of Changes
Other Study ID Numbers: A00-M105-13A
First Posted: April 10, 2014    Key Record Dates
Last Update Posted: September 13, 2016
Last Verified: September 2016

Keywords provided by George Thanassoulis, McGill University Health Center:
aortic stenosis

Additional relevant MeSH terms:
Nicotinic Acids
Aortic Valve Stenosis
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs