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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by McGill University Health Center
Sponsor:
Collaborators:
Jewish General Hospital
Laval University
Quebec Heart Institute
Information provided by (Responsible Party):
George Thanassoulis, McGill University Health Center
ClinicalTrials.gov Identifier:
NCT02109614
First received: April 4, 2014
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Aortic Stenosis and Lipoprotein(a) Levels
Drug: Extended release Niacin
Drug: Placebo Comparator
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by McGill University Health Center:

Primary Outcome Measures:
  • Calcium score progression by cardiac CT in individuals randomized to niacin as compared to those randomized to placebo [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean change in Lp(a) levels between treatment arms [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Rates of valve disease progression by echocardiography at 1 and 2 years [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
    Change in peak velocity (in m/s); Change in mean gradient (in mm Hg); Change in AV area (in cm2)

  • Drug compliance [ Time Frame: At 6, 12, 18 and 24 months ] [ Designated as safety issue: Yes ]
    Pill count and drug diary

  • Side effects and adverse events [ Time Frame: at 6, 12, 18 and 24 months ] [ Designated as safety issue: Yes ]
    all common and rare serious side-effects/adverse events will be monitored


Estimated Enrollment: 238
Study Start Date: April 2014
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02109614

Contacts
Contact: Kimberley V Kotar, B.Sc 514-934-1934 ext 35661 kimberleykotar@much.mcgill.ca
Contact: George Thanassoulis, MD 514-934-1934 george.thanassoulis@mcgill.ca

Locations
Canada, Quebec
MUHC - Royal Victoria Hospital Not yet recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: Kimberley V Kotar, B.Sc    514934-1934 ext 35166    kimberley.kotar@muhc.mcgill.ca   
Contact: George Thanassoulis, MD    514-934-1934 ext 35465    george.thanassoulis@mcgill.ca   
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    kimberley.kotar@muhc.mcgill.ca   
Contact: Mark Eisenberg, MD    514-340-8222    mark.eisenberg@mcgill.ca   
Principal Investigator: Mark Eisenberg, md         
MUHC - Montreal General Hospital Not yet recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: Kimberley V Kotar, BSc    5149341934 ext 35661    kimberley.kotar@muhc.mcgill.ca   
Principal Investigator: George Thanassoulis, MD MSc FRCPC         
Sponsors and Collaborators
George Thanassoulis
Jewish General Hospital
Laval University
Quebec Heart Institute
  More Information

Publications:
Responsible Party: George Thanassoulis, MD MSc FRCPC, McGill University Health Center
ClinicalTrials.gov Identifier: NCT02109614     History of Changes
Other Study ID Numbers: A00-M105-13A
Study First Received: April 4, 2014
Last Updated: April 7, 2014
Health Authority: Canada: Canadian Institutes of Health Research

Keywords provided by McGill University Health Center:
lipoprotein(a)
aortic stenosis

Additional relevant MeSH terms:
Niacin
Aortic Valve Stenosis
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Vasodilator Agents
Cardiovascular Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014