Early Aortic Valve Lipoprotein(a) Lowering Trial

NCT02109614 | Withdrawn Early Phase 1

• 1 other identifier: A00-M105-13A
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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.

Conditions

Aortic Stenosis and Lipoprotein(a) Levels

Keywords

lipoprotein(a); aortic stenosis

Outcome Measures

Primary Outcomes (1)

• Calcium score progression by cardiac CT in individuals randomized to niacin as compared to those randomized to placebo

  2 years

Secondary Outcomes (1)

• Mean change in Lp(a) levels between treatment arms

  2 years

Other Outcomes (3)

• Rates of valve disease progression by echocardiography at 1 and 2 years

  1 and 2 years

• Drug compliance

  At 6, 12, 18 and 24 months

• Side effects and adverse events

  at 6, 12, 18 and 24 months

Study Arms (2)

Extended release Niacin

EXPERIMENTAL

Taking 1500-2000mg niacin daily

Drug: Extended release Niacin

No Naicin

PLACEBO COMPARATOR

Placebo Comparator arm will be taking 1500mg of placebo daily

Drug: Placebo Comparator

Interventions

Extended release Niacin DRUG

Arm will be taking 1500-2000mg of niacin daily to see if lipoprotein(a) levels are lowered and aortic stenosis does not increase.

Extended release Niacin

Placebo Comparator DRUG

Placebo Comparator arm will be taking 1500mg of the placebo daily

No Naicin

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>50 years and \< 85 years
• 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).

You may not qualify if:

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

Sponsors & Collaborators

• George Thanassoulis: lead
• Jewish General Hospital: collaborator
• Laval University: collaborator
• Quebec Heart Institute: collaborator

Study Sites (3)

MUHC - Montreal General Hospital

Montreal, Quebec, H3A 1A1, Canada

Location

MUHC - Royal Victoria Hospital

Montreal, Quebec, H3A 1A1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (1)

• Thanassoulis G, Campbell CY, Owens DS, Smith JG, Smith AV, Peloso GM, Kerr KF, Pechlivanis S, Budoff MJ, Harris TB, Malhotra R, O'Brien KD, Kamstrup PR, Nordestgaard BG, Tybjaerg-Hansen A, Allison MA, Aspelund T, Criqui MH, Heckbert SR, Hwang SJ, Liu Y, Sjogren M, van der Pals J, Kalsch H, Muhleisen TW, Nothen MM, Cupples LA, Caslake M, Di Angelantonio E, Danesh J, Rotter JI, Sigurdsson S, Wong Q, Erbel R, Kathiresan S, Melander O, Gudnason V, O'Donnell CJ, Post WS; CHARGE Extracoronary Calcium Working Group. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013 Feb 7;368(6):503-12. doi: 10.1056/NEJMoa1109034.

  PMID: 23388002 BACKGROUND

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD MSc FRCPC

Study Record Dates

• First Submitted: April 4, 2014
• First Posted: April 10, 2014
• Study Start: May 1, 2014
• Primary Completion: January 1, 2017
• Study Completion: September 1, 2017
• Last Updated: October 25, 2023

Record last verified: 2023-10

Locations

CA (3)