Novel Pathways to Manage Inflammation and Atherosclerosis in Dialysis Patients: Role of Nicotinic Acid

Study Overview
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Brief Summary
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Patients with kidney failure on hemodialysis have an extremely high rate of cardiovascular disease including atherosclerotic cardiovascular disease. This, at least in part, is due to the chronic inflammatory status usually seen in these patients. Here we try to see if treatment with extended release nicotinic acid (Niaspan) can reduce their overall inflammatory burden (in general) and the atherosclerotic plaque inflammation (in particular).

Official Title
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Novel Pathways to Manage Inflammation and Atherosclerosis in Dialysis Patients: Role of Nicotinic Acid

Conditions
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Dialysis, Cardiovascular Disease, Atherosclerosis, Inflammation

Intervention / Treatment
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* Drug: Extended Release Nicotinic Acid (Niaspan)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A signed consent form; Male or Female, 18 years or older; Diagnosed with ESRD, on maintenance hemodialysis for at least six (6) months; Subject must be able to understand and provide informed consent; No known contraindications to therapy with nicotinic acid; Female subjects of childbearing potential must be willing to be on an acceptable form of birth control for the duration of the study and for two month after they have stopped taking the study drug. Exclusion Criteria: Any patient with a medical condition or taking any medications that would be contraindicated with the use of extended release niacin, such as active peptic ulcer disease; History of severe allergic reactions to the study medication; History of active infection or acute gouty attack within 2 weeks prior to enrollment; Known serological positivity for HIV, HBsAg, or HCV Ab; HbA1C > 9; Total CK of more than three times of the upper limit of normal; Elevation of liver function tests at time of entry (AST and/or ALT > 2 times the upper limit of normal); History of drug, alcohol, or chemical abuse within 6 months prior to enrollment; History of malignancy except adequately treated in-situ cervical carcinoma, or adequately treated basal or squamous cell carcinoma of the skin; History of an inflammatory disease such as SLE, rheumatoid arthritis or ulcerative colitis; Patients currently on pharmacological doses of nicotinic acid; Patients receiving chronic anti-inflammatory therapy; Patients with average baseline hs-CRP levels of > 20 mg/L or < 1 mg/L; Patients in whom FDG-PET/CT dual scans are contraindicated (e.g., pregnant patients or those with severe allergy to IV contrast; a pregnancy test will be performed in each female subject between 18 and 45 years of age prior to each scan)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: This study has only one arm.<br>Blood sample and scan results to be compared before and after intervention in each subject. | Drug: Extended Release Nicotinic Acid (Niaspan)<br>* Subjects will start on 500 mg per day of Niaspan for 4 weeks, then the dose will be increased to 1000 mg per day of Niaspan for 4 weeks, then the dose will be increased to 1500 mg of Niaspan per day for 4 weeks, after this subjects with weight of less than 60 kg will continue at 1500 mg per day of Niaspan for another 12 weeks whereas in subjects with weight of more than 60 kg the dose will be increased to 2000 mg of Niaspan per day which will be continued for 12 weeks.<br>* Other names: Niaspan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in FDG-PET/CT Dual Scan Score |  | 6 months | 
| Changes in Hs-CRP Level | Change in hs-CRP level before and after treatment in each subject | 6 months | 
| Changes in IL-6 Level | Change in IL-6 level before and after treatment in each subject | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Albumin Level | Pre and Post levels. | 6 months | 
| ESA (Erythorpoietic Stimulating Agent) Dose Requirement | Comparison of the average ESA dose used in the 3 month before and the last 3 months of the study. | 6 months | 
| Hemoglobin Level | Pre and Post Levels | 6 months | 
| Rate of Cardiovascular Events | Comparison of the average major cardiovascular events (myocardial infarction and/or stroke) in the 3 month before and the last 3 months of the study. | 6 months | 
| Hemodialysis Access Stenosis/Thrombosis | Comparison of the average hemodialysis access stenosis/thrombosis requiring intervention in the 3 month before and the last 3 months of the study. | 6 months | 
| Number of Completed Subjects With Significant Increase in ALT (Alanine Aminotransferase). | The number of subjects with significant rise in ALT but not to the extent requiring removal from the study (rise to more than 3 times the upper limit of the normal range) | 6 months (checked monthly) |