Aortic Stenosis and Lipoprotein(a) LevelsEarly Phase 1EAVaLLNCT02109614
Early Aortic Valve Lipoprotein(a) Lowering Trial
A Early Phase 1 study testing Extended release Niacin in people with Aortic Stenosis and Lipoprotein(a) Levels, run by George Thanassoulis at 3 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Aortic Stenosis and Lipoprotein(a) Levels
- What is being tested?
- Extended release Niacin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 3 sitesCanada
- Study dates
- May 2014to Sep 2017
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
MUHC - Montreal General Hospital
Montreal, Quebec, H3A 1A1
MUHC - Royal Victoria Hospital
Montreal, Quebec, H3A 1A1
Jewish General Hospital
Montreal, Quebec, H3T 1E2
About this study
Official title: A Pilot,Randomized Controlled-trial of Lipoprotein(a) Lowering for the Prevention of Aortic Valve Disease-translating Genomic Knowledge for Cardiovascular Prevention
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
Read more
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.
Read the detailed description
Screening: Potentially eligible participants from the echocardiography laboratory will be screened by a member of the research team for inclusion and exclusion criteria and will be asked to review and sign a consent form that explains the study.
Run-in: Participants with elevated Lp(a) and normal liver and renal indices, that meet all other inclusion and exclusion criteria will be started on low dose niacin (500 mg/d) for a 6 week run-in phase prior to randomization to assess tolerability and compliance to the intervention. The niacin dose will be increased by 500 mg increments weekly, as tolerated, to a maximum of 1500 mg/day (Participants who remain compliant >85% (by pill count and self-report) and who tolerate at least 1500 mg/d of niacin for at least 2 weeks will then undergo randomization to 1500 mg/d of immediate release niacin or matching placebo.
Randomization: will be performed via an Internet website where each participant will be given a unique identifier that matches the allocated drug kit.Blocking using random blocks of 2 and 4 will ensure that similar numbers of patients are randomized to the two arms of the study at each of the study centers.
The study will be double blind - neither patients, physicians, nor study personnel will know which participants are receiving active treatment.
After a 6-week run-in phase, participants able to tolerate the intervention will be randomized 1:1 to niacin extended release or placebo. After randomization, the treatment phase will be for 2 years (104 weeks). Data will be collected during 5 visits: (i) Randomization visit; (ii) 6-month follow-up visit; (iii) 12-month follow-up visit; (iv) 18-month follow-up visit; (v)Final visit (24-month).
(i) Randomization visit (baseline)
(1) Data Collected: A. Clinical and Biochemical Data B. Echocardiogram C. Blood Collection D. Cardiac CT
(ii) Follow-up visits (at 6, 12 and 18 months from randomization) Collection of clinical data (re: side-effects), compliance to therapy and blood.
(iii) Final visit (24 months) At the final visit, all usual data collected during the above follow-up visits will be obtained (including compliance, side-effects, etc). An echocardiogram, cardiac CT and a final blood test will also be obtained
- Primary Endpoints
- Relative reduction in rates of calcium score progression by cardiac CT in individuals randomized to niacin as compared to those randomized to placebo.
- Secondary Endpoints
- Number needed to screen to identify eligible participants
- Difference in mean change in Lp(a) levels between treatment arms
- Rates of progression in each arm by echocardiography at 1 and 2 years (Change in peak velocity (in m/s); Change in mean gradient (in mm Hg); Change in AVA (in cm2)
- Tertiary Endpoints
- Compliance (as a proportion of pills taken/pills prescribed) with niacin treatment
- Rates of side-effects and other adverse events
- Being tested
- Extended release Niacin, Placebo Comparator
- Keywords
- lipoprotein(a), aortic stenosis
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extended release NiacinDrug
Arm will be taking 1500-2000mg of niacin daily to see if lipoprotein(a) levels are lowered and aortic stenosis does not increase.
Placebo ComparatorDrug
Placebo Comparator arm will be taking 1500mg of the placebo daily
| Study group | Role | What they receive |
|---|---|---|
| Extended release Niacin | Experimental | Taking 1500-2000mg niacin daily Receives: Drug: Extended release Niacin |
| No Naicin | Placebo comparator | Placebo Comparator arm will be taking 1500mg of placebo daily Receives: Drug: Placebo Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Calcium score progression by cardiac CT in individuals randomized to niacin as compared to those randomized to placebo
Measured: 2 years
Secondary outcomes (1)
Mean change in Lp(a) levels between treatment arms
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2014 (estimated)
- Study startMay 2014
- Primary completionJan 2017 (estimated)
- Study completionSep 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aortic Stenosis and Lipoprotein(a) LevelsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- George Thanassoulis
- Sponsor type
- University, hospital or other
- Collaborators
- Jewish General Hospital, Laval University, Quebec Heart Institute
- Responsible party
- Sponsor-investigator, George Thanassoulis, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02109614
- Sponsor's protocol ID
- A00-M105-13A
- Acronym
- EAVaLL
- Status last verified
- Oct 2023
- First submitted
- 4 Apr 2014
- Last updated
- 25 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23388002
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot,Randomized Controlled-trial of Lipoprotein(a) Lowering for the Prevention of Aortic Valve Disease-translating Genomic Knowledge for Cardiovascular Prevention
- ClinicalTrials.gov ID
- NCT02109614
- Acronym / sponsor ID
- EAVaLL / A00-M105-13A
- Keywords
- lipoprotein(a), aortic stenosis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- George ThanassoulisUniversity, hospital or other
- Collaborators
- Jewish General Hospital, Laval University, Quebec Heart Institute
- Study start
- May 2014
- Primary completion
- Jan 2017 (estimated)
- Study completion
- Sep 2017 (estimated)
- First posted
- 10 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Screening: Potentially eligible participants from the echocardiography laboratory will be screened by a member of the research team for inclusion and exclusion criteria and will be asked to review and sign a consent form that explains the study.
Run-in: Participants with elevated Lp(a) and normal liver and renal indices, that meet all other inclusion and exclusion criteria will be started on low dose niacin (500 mg/d) for a 6 week run-in phase prior to randomization to assess tolerability and compliance to the intervention. The niacin dose will be increased by 500 mg increments weekly, as tolerated, to a maximum of 1500 mg/day (Participants who remain compliant >85% (by pill count and self-report) and who tolerate at least 1500 mg/d of niacin for at least 2 weeks will then undergo randomization to 1500 mg/d of immediate release niacin or matching placebo.
Randomization: will be performed via an Internet website where each participant will be given a unique identifier that matches the allocated drug kit.Blocking using random blocks of 2 and 4 will ensure that similar numbers of patients are randomized to the two arms of the study at each of the study centers.
The study will be double blind - neither patients, physicians, nor study personnel will know which participants are receiving active treatment.
After a 6-week run-in phase, participants able to tolerate the intervention will be randomized 1:1 to niacin extended release or placebo. After randomization, the treatment phase will be for 2 years (104 weeks). Data will be collected during 5 visits: (i) Randomization visit; (ii) 6-month follow-up visit; (iii) 12-month follow-up visit; (iv) 18-month follow-up visit; (v)Final visit (24-month).
(i) Randomization visit (baseline)
(1) Data Collected: A. Clinical and Biochemical Data B. Echocardiogram C. Blood Collection D. Cardiac CT
(ii) Follow-up visits (at 6, 12 and 18 months from randomization) Collection of clinical data (re: side-effects), compliance to therapy and blood.
(iii) Final visit (24 months) At the final visit, all usual data collected during the above follow-up visits will be obtained (including compliance, side-effects, etc). An echocardiogram, cardiac CT and a final blood test will also be obtained
- Primary Endpoints
- Relative reduction in rates of calcium score progression by cardiac CT in individuals randomized to niacin as compared to those randomized to placebo.
- Secondary Endpoints
- Number needed to screen to identify eligible participants
- Difference in mean change in Lp(a) levels between treatment arms
- Rates of progression in each arm by echocardiography at 1 and 2 years (Change in peak velocity (in m/s); Change in mean gradient (in mm Hg); Change in AVA (in cm2)
- Tertiary Endpoints
- Compliance (as a proportion of pills taken/pills prescribed) with niacin treatment
- Rates of side-effects and other adverse events
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Extended release Niacin | Experimental | Drug: Extended release NiacinTaking 1500-2000mg niacin daily |
| No Naicin | Placebo comparator | Drug: Placebo ComparatorPlacebo Comparator arm will be taking 1500mg of placebo daily |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age >50 years and < 85 years
- Aortic sclerosis OR mild AS
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Extended release NiacinArm will be taking 1500-2000mg of niacin daily to see if lipoprotein(a) levels are lowered and aortic stenosis does not increase. | Drug | Extended release Niacin |
| Placebo ComparatorPlacebo Comparator arm will be taking 1500mg of the placebo daily | Drug | No Naicin |
Primary outcome
Calcium score progression by cardiac CT in individuals randomized to niacin as compared to those randomized to placebo
Time frame: 2 years
1 secondary outcome
Mean change in Lp(a) levels between treatment arms
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2023.
- Background: PubMed 23388002Thanassoulis 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Extended release Niacin in people with Aortic Stenosis and Lipoprotein(a) Levels, run by George Thanassoulis at 3 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 25 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Calcium score progression by cardiac CT in individuals randomized to niacin as compared to those randomized to placebo (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02109614, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2023.