Effect of Niaspan on Cholesterol in Men

Effect of Niaspan on Parameters of Reverse Cholesterol Transport and HDL-C Subclasses in Male Subjects With Low HDL-C Levels

To determine whether 8 weeks of Niaspan treatment increases cholesterol efflux in male subjects with low HDL-C cholesterol when compared to no treatment.

To determine whether 8 weeks of Niaspan treatment increases fecal cholesterol excretion when compared to no treatment.

To determine whether 8 weeks of Niaspan treatment increases the rate of global reverse cholesterol transport when compared to no treatment.

This will be a single center, open-label, randomized, mechanism of action study consisting of 8 weeks of active treatment preceded by a screening phase from one to 8 weeks and a baseline measurement of parameters of reverse cholesterol transport for 10 days. The population for this trial is 15 non-diabetic men aged 18-70 years. Ten subjects will be low HDL-C male volunteers who will receive aspirin and Niaspan and five subjects will be low HDL-C male volunteers who will receive only aspirin.

Inclusion Criteria:

Subjects meeting the following criteria at the Screening Visit will be eligible to participate:

• Provide written informed consent
• Male
• Age 18 to 70 years
• BMI 18.5-40 kg/m2
• HDL-C values <40 mg/dL
• Triglyceride value 150-500 mg/dL.
• Good health based on medical history, physical examination and laboratory safety tests performed at the screening visit or prior to initial dose of study medication.
• No clinically significant abnormality on ECG performed at the screening visit or prior to initial dose of study medication.
• Non-smoker and no other use of nicotine containing products for at least 6 months and does not plan to begin smoking during the course of the study.
• Dietary or nutritional remedies including plant sterol containing products (i.e. Benecol, SmartBalance, etc) of any sort for at least 2 weeks prior to and throughout the study.
• Willing to avoid the use of lipid modifying medications (excluding statins) such as the fibrates, cholestyramine, fish oil, and ezetimibe within 8 weeks prior to and during the study.
• Avoidance of extreme change of physical activity from screening through the follow-up period.

Exclusion Criteria:

Subjects are excluded from participation in the study if any of the following criteria apply:

• History of intolerance to Niacin or Niaspan.
• Treatment with Niacin or Niaspan in the past 3 months (Multivitamin use with non-pharmacologic doses of Niacin - less than 500mg per day - is allowed).
• History of stroke, chronic seizures, or major neurological disorder.
• Significant emotional problems or a history of clinically significant psychiatric disorder.
• Bleeding diathesis or intolerance to aspirin.
• Anemia as defined as a hematocrit < 25%.
• History of gastritis, bleeding gastric or duodenal ulcers.
• History Type 1 or Type 2 diabetes, or fasting plasma glucose >125 mg/dL at screening or 75 gm OGTT with 2 hour glucose >140mg/dL.
• History of illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk through participation.
• History of ileal bypass, gastric bypass, or other condition associated with malabsorption.
• Abnormal thyroid function tests.
• AST or ALT > 1.5x the upper limit of normal.
• Active or recent gastrointestinal condition such as gastroenteritis, irritable bowel syndrome, chronic constipation, or diarrhea which may affect bowel movements.
• History of plant sterol storage disease or a history of intolerance to plant sterols or plant sterol containing products.
• History of neoplastic disease (i.e. leukemia, lymphoma, malignant melanoma), or myeloproliferative disease, regardless of the time since treatment. Exceptions include adequately treated non-melanomatous skin carcinoma, and other malignancies that may have been treated successfully >10 years prior to the screening visit with no evidence of recurrence.
• Excessive alcohol consumption defined as > three glasses of alcoholic beverages or distilled spirits per day. *** Must avoid excessive alcohol consumption throughout study.
• Currently using psyllium or other fiber based laxatives, phytosterol margarines, and/or over the counter (OTC) treatments that are known to affect serum lipids and has NOT been treated with a stable regimen for > 6 weeks prior to screening (Visit 1) or the subject DOES NOT agree to continue this regimen for the duration of the clinical trial.
• Regular user of illicit drugs or history of drug abuse (including alcohol) within the previous 2 years.
• Use of anabolic agents.
• Any condition or therapy which, in the opinion of the investigator, poses a risk to the subject
• Use of any investigational drug within 30 days before screening