Randomized, Controlled Trial of Extended-Release Niacin (Niaspan®) to Augment Subacute Ischemic Stroke Recovery

Phase II, Randomized, Double-Blinded, Placebo-Controlled Trial of Extended-Release Niacin (Niaspan®) to Augment Subacute Ischemic Stroke Recovery

The purpose of this study is to determine the safety, tolerability, and to explore the possible benefit of extended-release niacin (Niaspan®) in attempting to improve the recovery of patients after ischemic stroke.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Placebo; Drug: Extended-Release Niacin; Drug: Extended-Release Niacin

Detailed Description

The investigators are interested in extended-release niacin (Niaspan®) and its potential restorative role after ischemic stroke. At Henry Ford Hospital in Detroit, Michigan, extended-release niacin (Niaspan®) has been shown to improve the functional outcomes of rats when administered during the first two weeks after ischemic stroke onset. Such results are encouraging and warrant further investigation in humans. The specific aims of this study are to prospectively evaluate the use of extended-release niacin (Niaspan®) in a phase II clinical trial in patients with subacute ischemic stroke. The investigators will assess the safety and tolerability of Niaspan® and evaluate outcomes among treated patients at 24 weeks after ischemic stroke onset. This will be a randomized, double-blinded, placebo-controlled, safety, tolerability, and exploratory efficacy study of extended-release niacin (Niaspan®) in subacute ischemic stroke patients with both low HDL-C and normal HDL-C in cohort sizes of 16 patients. A total enrollment of 48 patients is planned. Patients who are between 72 hours and 7 days from stroke onset will receive Niaspan® 500mg, 1000mg, or placebo daily for a period of 24 weeks. Evaluation of potential safety and tolerability in subacute ischemic stroke patients will be made during the course of treatment and at formal visits at 6, 12, and 24 weeks. The primary safety measures will be death, recurrent stroke, myocardial infarction, and neurological worsening during treatment. Exploratory analysis will include functional outcomes on the NIHSS scores, modified Rankin scores, and Barthel indices at 24 weeks. The goal of this study is to improve the outcomes from ischemic stroke, using a safe and effective novel strategy of restoration, which has been translated from basic laboratory studies.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with clinical ischemic stroke able to enroll between 72 hours and 7 days after symptom onset.
• Patients age 18-85, inclusive.
• NIHSS score of 4-21, inclusive, prior to treatment.
• Signed IRB-approved informed consent by patient or authorized representative.

Exclusion Criteria:

General

• Participation in another study with an investigational drug or device.
• Women known to be pregnant, lactating, or of childbearing potential with a positive urine beta-HCG.
• Patients using niacin within the 7 days previous to their stroke.

Safety Related

• Unstable angina.
• Acute Myocardial infarction.
• Concurrent arterial bleeding.
• Active peptic ulcer disease.
• Platelet count less than 100,000 per microliter.
• Internationally Normalized Ratio (INR) greater than 1.3 without use of warfarin.
• Concurrent use of bile acid sequestrants (colestipol and cholestyramine)
• Baseline systolic blood pressure less than 100 mmHg.
• History of significant hepatic dysfunction.
• Allergy or hypersensitivity to aspirin.
• Concurrent use of amiodarone, gemfibrozil, fibrate or other bile acid resin, cyclosporine, itraconazole, ketaconazole, telithromycin, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, danazol.
• Allergy or hypersensitivity to extended-release niacin.
• Allergy or hypersensitivity to statin agents.

Potentially Interfering with Outcomes Assessment

• Prior history of dementia.
• Patients without fixed address or those deemed unlikely to present for follow-up by the investigator.
• Patients whose life expectancy is less than 24 weeks.
• Pre-stroke modified Rankin score>2.
• Glucose less than 50 mg/dl.
• Other serious illness (e.g., severe hepatic, cardiac, or renal failure; or a complex disease that may confound treatment assessment).

Imaging Related

• Evidence of primary intra-parenchymal hemorrhage on initial neuroimaging study.
• Neuroimaging evidence of a nonvascular cause for the neurological symptoms.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo tablet once daily
Experimental: Niaspan® 500mg	Drug: Extended-Release Niacin; 500mg tablet once daily; Other Names: Niaspan®; Drug: Extended-Release Niacin; 1000mg tablet once daily; Other Names: Niaspan®
Experimental: Niaspan® 1000mg	Drug: Extended-Release Niacin; 500mg tablet once daily; Other Names: Niaspan®; Drug: Extended-Release Niacin; 1000mg tablet once daily; Other Names: Niaspan®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of expected serious adverse events	Analysis of the frequency and type of serious adverse events among patients in each study arm	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Recovery	Exploratory efficacy analysis of the differences in functional recovery between each study arm as measured using the modified Rankin Scale, NIH Stroke Scale, and Barthel Index.	24 weeks

Collaborators and Investigators

• Sponsor: Henry Ford Health System
• Investigators: Principal Investigator: Andrew N. Russman, D.O., Henry Ford Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: November 21, 2008
• First Submitted That Met QC Criteria: November 21, 2008
• First Posted (Estimate): November 24, 2008

Study Record Updates

• Last Update Posted (Estimate): September 14, 2012
• Last Update Submitted That Met QC Criteria: September 12, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Ischemic Stroke; Recovery of Function; Extended-release niacin
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; 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: HFHS-5284