Aortocoronary Saphenous Vein Bypass Graft AtherosclerosisPhase 2ALPINE-SVGNCT01221402

Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis

A Phase 2 study testing extended-release niacin (Niaspan) in people with Aortocoronary Saphenous Vein Bypass Graft Atherosclerosis and Intermediate Saphenous Vein Graft Lesions, run by North Texas Veterans Healthcare System at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Intermediate saphenous vein graft (SVG) lesions are common, have high rates of progression to severe lesions or occlusion, and are associated with high incidence of adverse clinical outcomes. The ALPINE-SVG trial is a randomized-controlled trial of extended-release niacin vs. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Aortocoronary Saphenous Vein Bypass Graft Atherosclerosis, Intermediate Saphenous Vein Graft Lesions
What is being tested?: extended-release niacin (Niaspan)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 38 participants
Where: 1 siteUnited States
Study dates: Oct 2010to Nov 2015
Phase: Phase 2
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age 18 years or greater
Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up.
Undergoing clinically-indicated coronary and SVG angiography
Have an intermediate SVG lesion (defined as a lesion 30-60% angiographic diameter stenosis) without previous percutaneous intervention, amenable to examination with IVUS. The lesion should have no thrombus or ulceration and should not be considered responsible for the patient's clinical presentation and referral for graft angiography.

Who cannot join

Known allergy to niacin
History of statin-induced myopathy
Positive pregnancy test or breast-feeding
Coexisting conditions that limit life expectancy to less than 12 months or that could affect a patient's compliance with the protocol
Uncontrolled fasting triglyceride levels ( 500 mg/dL)
Fasting LDL-C >200 mg/dL

Show all 22Show fewer

Fasting HDL-C >60 mg/dL
Poorly controlled diabetes (glycosylated hemoglobin levels 10%)
Current active liver disease or hepatic dysfunction
AST or ALT > 2x the upper limit of normal
Uncontrolled hypothyroidism (Thyroid Stimulating Hormone >1.5 x upper limit of normal [ULN])
Unexplained creatine kinase elevations (>3 x ULN)
Recent history of acute gout
Serum creatinine > 2.5 mg/dL
HIV (due to potential anti-retroviral drug-interactions with niacin)
Use of high-dose, antioxidant vitamins (vitamins C, E, or beta-carotene) that may interfere with the HDL-raising effect of niacin
Severe peripheral arterial disease limiting vascular access
Referral for cardiac catheterization by a physician who is an investigator in the present study.
Symptoms consistent with moderate or greater severity of congestive heart failure (New York Heart Association - NYHA class III or IV) or whose most recent determination of left ventricular ejection fraction is <25%
Uncontrolled hypertension, defined as either a resting diastolic blood pressure of ≥100 mmHg or a resting systolic blood pressure of ≥200 mmHg
History of allergic reaction to iodine-based contrast agents
Significant medical or psychological condition that, in the opinion of the investigator, may compromise the patient's safety or successful participation in the study

Trial locations and contacts

1 site in 1 country.

United States1 site

VA North Texas Healthcare System
Dallas, Texas, 75216

Other trials in United States

About this study

Official title: Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis: The Atherosclerosis Lesion Progression Intervention Using Niacin Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial

Intermediate saphenous vein graft (SVG) lesions are common, have high rates of progression to severe lesions or occlusion, and are associated with high incidence of adverse clinical outcomes.

The ALPINE-SVG trial is a randomized-controlled trial of extended-release niacin vs. placebo in patients with intermediate saphenous vein graft lesions. The main hypothesis of the study is that compared to placebo, niacin administration will result in reduction in percent atheroma volume at 12-month follow-up angiography.

Read the detailed description

This is a phase II, single-center, double-blind trial that will randomize 138 prior CABG patients with an intermediate SVG lesion (30%-60% angiographic diameter stenosis) on clinically-indicated coronary angiography, and HDL-C<60 mg/dL to ER-niacin at a dose of 1500-2000 mg daily or matching placebo (containing 50 mg of niacin that can cause flushing but has no lipid lowering effect) for 12 months. All patients will receive a statin with goal LDL-C <70 mg/dL. Coronary angiography, intravascular ultrasonography (IVUS), and intravascular near-infrared intracoronary spectroscopy (NIRS), and optical coherence tomography (OCT) of the intermediate SVG lesion will be performed at enrollment and after 12 months in each patient, along with exercise stress testing at 1 month and 12 months, B-mode carotid ultrasound imaging at enrollment and after 6 and 12 months, reactive hyperemia peripheral arterial tonometry (RH-PAT) at enrollment and after 6 and 12 months, and with peripheral blood sampling performed at enrollment and at 1, 3, 6, 9 and 12 months, to determine whether compared to placebo, administration of ER-niacin will result in:

Reduction of the percent atheroma volume (PAV) of the intermediate SVG lesion at 12-month follow-up IVUS imaging (primary endpoint)
Reduction of total and normalized total intermediate SVG lesion atheroma volume, reduction of atheroma volume in the most diseased 10-mm subsegment of the target intermediate lesion, reduction of atheroma volume in the subsegment of the target intermediate lesion with lipid core plaque by NIRS, reduction of lipid core burden index as assessed by near-infrared intracoronary spectroscopy, increase in fibrous cap thickness and reduction in the prevalence and number of microchannels, in the presence and extent of necrotic lipid pool, plaque rupture, calcification, and thrombus, as assessed by optical coherence tomography, and reduction of angiographic intermediate SVG target lesion failure at 12-month follow-up SVG imaging (secondary endpoints)
Increased exercise capacity and reduction in ischemia, as assessed by exercise stress testing between 1 and 12 months (secondary endpoint)
Less increase in mean carotid intima-media thickness at 6 and 12 months (secondary endpoint)
Greater increase in natural logarithmic scaled reactive hyperemia index (L_RHI) at 6 and 12 months (secondary endpoint)
Greater increase in EPC-CFU/mL of peripheral blood from baseline to 1, 3, 6, and 12 months post enrollment (secondary endpoint)
Reduction of major adverse cardiac events (defined as the composite of death, acute coronary syndrome, or coronary revascularization) during follow-up (secondary endpoint)

Conditions: Aortocoronary Saphenous Vein Bypass Graft Atherosclerosis, Intermediate Saphenous Vein Graft Lesions
Being tested: extended-release niacin (Niaspan)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

extended-release niacin (Niaspan)Drug
Patients will be randomized in a 1:1 ratio to receive extended-release niacin (1500 - 2000 mg per day) or matching placebo that contains 50 mg of crystalline niacin (enough to cause flushing but has no effect on lipid levels).

Study groups in NCT01221402
Study group	Role	What they receive
Extended-release niacin	Experimental	Not described Receives: Drug: extended-release niacin (Niaspan)
Placebo	Placebo comparator	Not described Receives: Drug: extended-release niacin (Niaspan)

What is being measured

The primary outcome is the main question the study is designed to answer.

change in percent atheroma volume at 12 months intravascular ultrasonography
Measured: 12 months

Secondary outcomes (11)

change in total and normalized total intermediate SVG lesion atheroma volume
Measured: 12 months
reduction of atheroma volume in the most diseased 10-mm subsegment of the target intermediate lesion
Measured: 12 months
reduction of atheroma volume in the subsegment of the target intermediate lesion with lipid core plaque by near-infrared spectroscopy
Measured: 12 months
lipid core burden index as assessed by near-infrared intracoronary spectroscopy
Measured: 12 months
increase in fibrous cap thickness and reduction in the prevalence and number of microchannels, in the presence and extent of necrotic lipid pool, plaque rupture, calcification, and thrombus, as assessed by optical coherence tomography
Measured: 12 months
angiographic intermediate SVG target lesion failure
Measured: 12 month
exercise capacity and ischemia, as assessed by exercise stress testing
Measured: 12 months
carotid intima-media thickness
Measured: 6 and 12 months
reactive hyperemia index
Measured: 12 months
EPC-CFU/mL of peripheral blood
Measured: 12 months
major adverse cardiac events (defined as the composite of death, acute coronary syndrome, or coronary revascularization)
Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2010Nov 2015

First posted15 Oct 2010 (estimated)
Study startOct 2010
Primary completionOct 2014
Study completionNov 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Aortocoronary Saphenous Vein Bypass Graft AtherosclerosisStudies 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: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Original plan was to enroll 138 subjects, but trial was terminated early and total randomized was 38.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 38 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01221402
Sponsor's protocol ID: 10-029
Other IDs: R01HL102442
Acronym: ALPINE-SVG
Status last verified: Aug 2017
First submitted: 14 Oct 2010
Last updated: 17 Aug 2017
Results posted: No
Data monitoring committee: Yes

Publications

Kotsia AP, Rangan BV, Christopoulos G, Coleman A, Roesle M, Cipher D, de Lemos JA, McGuire DK, Packer M, Banerjee S, Brilakis ES. Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis: Insights from the Atherosclerosis Lesion Progression Intervention Using Niacin Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial. J Invasive Cardiol. 2015 Oct;27(10):E204-10.
PubMed 26429851
Guerra A, Rangan BV, Coleman A, Xu H, Kotsia A, Christopoulos G, Sosa A, Chao H, Han H, Abdurrahim G, Roesle M, de Lemos JA, McGuire DK, Packer M, Banerjee S, Brilakis ES. Effect of Extended-Release Niacin on Carotid Intima Media Thickness, Reactive Hyperemia, and Endothelial Progenitor Cell Mobilization: Insights From the Atherosclerosis Lesion Progression Intervention Using Niacin Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial. J Invasive Cardiol. 2015 Dec;27(12):555-60.
PubMed 26630643

Study at a glance

From the registry record, last updated by the sponsor on 17 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis: The Atherosclerosis Lesion Progression Intervention Using Niacin Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial
ClinicalTrials.gov ID: NCT01221402
Acronym / sponsor ID: ALPINE-SVG / 10-029
Conditions: Aortocoronary Saphenous Vein Bypass Graft Atherosclerosis, Intermediate Saphenous Vein Graft Lesions
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 38 participants (actual)
Lead sponsor: North Texas Veterans Healthcare SystemUS federal agency
Collaborators: National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
Study start: Oct 2010
Primary completion: Oct 2014 (actual)
Study completion: Nov 2015 (actual)
First posted: 15 Oct 2010 (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.

Intermediate saphenous vein graft (SVG) lesions are common, have high rates of progression to severe lesions or occlusion, and are associated with high incidence of adverse clinical outcomes.

Detailed description

Reduction of the percent atheroma volume (PAV) of the intermediate SVG lesion at 12-month follow-up IVUS imaging (primary endpoint)
Reduction of total and normalized total intermediate SVG lesion atheroma volume, reduction of atheroma volume in the most diseased 10-mm subsegment of the target intermediate lesion, reduction of atheroma volume in the subsegment of the target intermediate lesion with lipid core plaque by NIRS, reduction of lipid core burden index as assessed by near-infrared intracoronary spectroscopy, increase in fibrous cap thickness and reduction in the prevalence and number of microchannels, in the presence and extent of necrotic lipid pool, plaque rupture, calcification, and thrombus, as assessed by optical coherence tomography, and reduction of angiographic intermediate SVG target lesion failure at 12-month follow-up SVG imaging (secondary endpoints)
Increased exercise capacity and reduction in ischemia, as assessed by exercise stress testing between 1 and 12 months (secondary endpoint)
Less increase in mean carotid intima-media thickness at 6 and 12 months (secondary endpoint)
Greater increase in natural logarithmic scaled reactive hyperemia index (L_RHI) at 6 and 12 months (secondary endpoint)
Greater increase in EPC-CFU/mL of peripheral blood from baseline to 1, 3, 6, and 12 months post enrollment (secondary endpoint)
Reduction of major adverse cardiac events (defined as the composite of death, acute coronary syndrome, or coronary revascularization) during follow-up (secondary endpoint)

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Original plan was to enroll 138 subjects, but trial was terminated early and total randomized was 38.

Arm	Type	Receives
Extended-release niacin	Experimental	Drug: extended-release niacin (Niaspan)
Placebo	Placebo comparator	Drug: extended-release niacin (Niaspan)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Age 18 years or greater
Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up.
Undergoing clinically-indicated coronary and SVG angiography
Have an intermediate SVG lesion (defined as a lesion 30-60% angiographic diameter stenosis) without previous percutaneous intervention, amenable to examination with IVUS. The lesion should have no thrombus or ulceration and should not be considered responsible for the patient's clinical presentation and referral for graft angiography.

Key exclusion criteria (22 listed)

Known allergy to niacin
History of statin-induced myopathy
Positive pregnancy test or breast-feeding
Coexisting conditions that limit life expectancy to less than 12 months or that could affect a patient's compliance with the protocol
Uncontrolled fasting triglyceride levels ( 500 mg/dL)

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 niacin (Niaspan)Patients will be randomized in a 1:1 ratio to receive extended-release niacin (1500 - 2000 mg per day) or matching placebo that contains 50 mg of crystalline niacin (enough to cause flushing but has no effect on lipid levels).	Drug	Extended-release niacin, Placebo

Primary outcome

change in percent atheroma volume at 12 months intravascular ultrasonography
Time frame: 12 months

11 secondary outcomes

change in total and normalized total intermediate SVG lesion atheroma volume
Time frame: 12 months
reduction of atheroma volume in the most diseased 10-mm subsegment of the target intermediate lesion
Time frame: 12 months
reduction of atheroma volume in the subsegment of the target intermediate lesion with lipid core plaque by near-infrared spectroscopy
Time frame: 12 months
lipid core burden index as assessed by near-infrared intracoronary spectroscopy
Time frame: 12 months
increase in fibrous cap thickness and reduction in the prevalence and number of microchannels, in the presence and extent of necrotic lipid pool, plaque rupture, calcification, and thrombus, as assessed by optical coherence tomography
Time frame: 12 months
angiographic intermediate SVG target lesion failure
Time frame: 12 month
exercise capacity and ischemia, as assessed by exercise stress testing
Time frame: 12 months
carotid intima-media thickness
Time frame: 6 and 12 months
reactive hyperemia index
Time frame: 12 months
EPC-CFU/mL of peripheral blood
Time frame: 12 months
major adverse cardiac events (defined as the composite of death, acute coronary syndrome, or coronary revascularization)
Time frame: 12 months

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2017.
Results publication: PubMed 26429851Kotsia AP, Rangan BV, Christopoulos G, Coleman A, Roesle M, Cipher D, de Lemos JA, McGuire DK, Packer M, Banerjee S, Brilakis ES. Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis: Insights from the Atherosclerosis Lesion Progression Intervention Using Niacin Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial. J Invasive Cardiol. 2015 Oct;27(10):E204-10.
Results publication: PubMed 26630643Guerra A, Rangan BV, Coleman A, Xu H, Kotsia A, Christopoulos G, Sosa A, Chao H, Han H, Abdurrahim G, Roesle M, de Lemos JA, McGuire DK, Packer M, Banerjee S, Brilakis ES. Effect of Extended-Release Niacin on Carotid Intima Media Thickness, Reactive Hyperemia, and Endothelial Progenitor Cell Mobilization: Insights From the Atherosclerosis Lesion Progression Intervention Using Niacin Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial. J Invasive Cardiol. 2015 Dec;27(12):555-60.

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.

Emmanouil S Brilakis, MD, PhD principal investigator

North Texas Veterans Healthcare System

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 4 inclusion and 22 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: finished, as of the sponsor's last update on 17 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

change in percent atheroma volume at 12 months intravascular ultrasonography (time frame: 12 months). 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 NCT01221402, which also lists 2 linked publications.

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 17 Aug 2017.