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

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).

Study Overview

• Status: Terminated
• Conditions: Inflammation; Cardiovascular Disease; Atherosclerosis; Dialysis
• Intervention / Treatment: Drug: Extended Release Nicotinic Acid (Niaspan)

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02130
      • BWH/FH/DCI Outpatient Dialysis Unit
    • Somerville, Massachusetts, United States
      • DCI Dialysis Unit-Somerville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: This study has only one arm.; Blood sample and scan results to be compared before and after intervention in each subject.

Drug: Extended Release Nicotinic Acid (Niaspan); 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.; Other Names: Niaspan; Extended Release Nicotinic Acid

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Kambiz Zandi-Nejad, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: July 7, 2010
• First Submitted That Met QC Criteria: July 7, 2010
• First Posted (ESTIMATE): July 9, 2010

Study Record Updates

• Last Update Posted (ACTUAL): June 28, 2017
• Last Update Submitted That Met QC Criteria: May 26, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Inflammation; Atherosclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 2010P001049