Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis (ALPINE-SVG)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Emmanouil Brilakis, North Texas Veterans Healthcare System
ClinicalTrials.gov Identifier:
NCT01221402
First received: October 14, 2010
Last updated: December 31, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Aortocoronary Saphenous Vein Bypass Graft Atherosclerosis
Intermediate Saphenous Vein Graft Lesions
Drug: extended-release niacin (Niaspan)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by North Texas Veterans Healthcare System:

Primary Outcome Measures:
  • change in percent atheroma volume at 12 months intravascular ultrasonography [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • change in total and normalized total intermediate SVG lesion atheroma volume [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • reduction of atheroma volume in the most diseased 10-mm subsegment of the target intermediate lesion [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • reduction of atheroma volume in the subsegment of the target intermediate lesion with lipid core plaque by near-infrared spectroscopy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • lipid core burden index as assessed by near-infrared intracoronary spectroscopy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • angiographic intermediate SVG target lesion failure [ Time Frame: 12 month ] [ Designated as safety issue: No ]
  • exercise capacity and ischemia, as assessed by exercise stress testing [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • carotid intima-media thickness [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • reactive hyperemia index [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • EPC-CFU/mL of peripheral blood [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • major adverse cardiac events (defined as the composite of death, acute coronary syndrome, or coronary revascularization) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 138
Study Start Date: October 2010
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Extended-release niacin Drug: 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).
Placebo Comparator: Placebo Drug: 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).

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:

  1. Reduction of the percent atheroma volume (PAV) of the intermediate SVG lesion at 12-month follow-up IVUS imaging (primary endpoint)
  2. 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)
  3. Increased exercise capacity and reduction in ischemia, as assessed by exercise stress testing between 1 and 12 months (secondary endpoint)
  4. Less increase in mean carotid intima-media thickness at 6 and 12 months (secondary endpoint)
  5. Greater increase in natural logarithmic scaled reactive hyperemia index (L_RHI) at 6 and 12 months (secondary endpoint)
  6. Greater increase in EPC-CFU/mL of peripheral blood from baseline to 1, 3, 6, and 12 months post enrollment (secondary endpoint)
  7. Reduction of major adverse cardiac events (defined as the composite of death, acute coronary syndrome, or coronary revascularization) during follow-up (secondary endpoint)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 years or greater
  2. Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up.
  3. Undergoing clinically-indicated coronary and SVG angiography
  4. 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.

Exclusion Criteria:

  1. Known allergy to niacin
  2. History of statin-induced myopathy
  3. Positive pregnancy test or breast-feeding
  4. Coexisting conditions that limit life expectancy to less than 12 months or that could affect a patient's compliance with the protocol
  5. Uncontrolled fasting triglyceride levels ( 500 mg/dL)
  6. Fasting LDL-C >200 mg/dL
  7. Fasting HDL-C >60 mg/dL
  8. Poorly controlled diabetes (glycosylated hemoglobin levels 10%)
  9. Current active liver disease or hepatic dysfunction
  10. AST or ALT > 2x the upper limit of normal
  11. Uncontrolled hypothyroidism (Thyroid Stimulating Hormone >1.5 x upper limit of normal [ULN])
  12. Unexplained creatine kinase elevations (>3 x ULN)
  13. Recent history of acute gout
  14. Serum creatinine > 2.5 mg/dL
  15. HIV (due to potential anti-retroviral drug-interactions with niacin)
  16. Use of high-dose, antioxidant vitamins (vitamins C, E, or beta-carotene) that may interfere with the HDL-raising effect of niacin
  17. Severe peripheral arterial disease limiting vascular access
  18. Referral for cardiac catheterization by a physician who is an investigator in the present study.
  19. 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%
  20. Uncontrolled hypertension, defined as either a resting diastolic blood pressure of ≥100 mmHg or a resting systolic blood pressure of ≥200 mmHg
  21. History of allergic reaction to iodine-based contrast agents
  22. Significant medical or psychological condition that, in the opinion of the investigator, may compromise the patient's safety or successful participation in the study
  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: NCT01221402

Locations
United States, Texas
VA North Texas Healthcare System
Dallas, Texas, United States, 75216
Sponsors and Collaborators
North Texas Veterans Healthcare System
Investigators
Principal Investigator: Emmanouil S Brilakis, MD, PhD North Texas Veterans Healthcare System
  More Information

No publications provided

Responsible Party: Emmanouil Brilakis, Director, Cardiac Catheterization Laboratories, North Texas Veterans Healthcare System
ClinicalTrials.gov Identifier: NCT01221402     History of Changes
Other Study ID Numbers: 10-029, R01HL102442
Study First Received: October 14, 2010
Last Updated: December 31, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Niacin
Nicotinic Acids
Niacinamide
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 September 18, 2014