Neuroprotection With Statin Therapy for Acute Recovery Trial (Neu-START)

This study has been completed.
Sponsor:
Information provided by:
Columbia University
ClinicalTrials.gov Identifier:
NCT00243880
First received: October 24, 2005
Last updated: January 12, 2011
Last verified: July 2010
  Purpose

The purpose of this dose escalation study is to evaluate the use of lovastatin for the treatment of acute ischemic stroke.


Condition Intervention Phase
Stroke
Drug: lovastatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: SPOTRIAS: Neuroprotection With Statin Therapy for Acute Recovery Trial

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • safety through 30 days defined as absence of liver or muscle-related toxicity on days 1, 2, 3, 5, 7, and 30. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Devt of clinical or laboratory evidence of major hepatic or muscle toxicity. Either: (1) liver toxicity: liver function test increase, devt jaundice, unexplained coagulopathy, or other clinical evidence of hepatitis or liver failure; or (2) muscle toxicity: increase in creatine phosphokinase (CK) at any time point


Secondary Outcome Measures:
  • pharmacokinetic measurements made on days 1, 3, 4, and 5. [ Time Frame: 5 days ]

Enrollment: 33
Study Start Date: September 2005
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1
lovastatin
Drug: lovastatin
investigators will treat the patients within 24 hours of symptom onset with short term high-dose lovastatin at escalating dosage. The escalating dosage levels will be 1, 3, 6, 8, and 10 mg/kg per day for 3 days.

Detailed Description:

The Neuroprotection with Statin Therapy for Acute Recovery Trial (Neu-START) is part of the Specialized Program on Translational Research in Acute Stroke (SPOTRIAS). The overall goals of SPOTRIAS are to enhance delivery of acute stroke patient care with a focus on high-risk, disadvantaged populations, train acute stroke translational researchers, and conduct 3 innovative acute stroke projects.

Neu-START will enroll 33 patients with acute ischemic stroke presenting within 24 hours of onset. In the trial, investigators will treat the patients within 24 hours of symptom onset with short term high-dose lovastatin at escalating dosage. The escalating dosage levels will be 1, 3, 6, 8, and 10 mg/kg per day for 3 days. Lovastatin is in a class of drugs called statins, used for lowering cholesterol and preventing cardiovascular disease. Patients will be followed for 30 days for clinical and laboratory outcome events.

The goals of this trial are to determine if lovastatin in increasing doses from 1 mg/kg to 10 mg/kg daily for 3 days beginning 24 hours after acute ischemic stroke can be administered safely, and to assess the pharmacokinetics of lovastatin administered at high doses.

  Eligibility

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

Inclusion Criteria:

  • Age >18
  • Satisfies the criteria for ischemic stroke: acute focal neurological deficit of likely ischemic vascular origin.
  • Patient or legally authorized representative has provided written informed consent prior to study entry.
  • Patient can receive the first treatment dose within 0-24 hours of stroke onset. For patients found with stroke on awakening, it will be assumed that the stroke occurred the last time that the patient was known to be normal.
  • Patient has pretreatment brain CT scan compatible with ischemic stroke and excludes hemorrhagic and non-vascular etiologies of symptoms.
  • Patients taking statins at time of stroke may be included.

Exclusion Criteria:

  • Brain imaging study shows a lesion other than ischemic stroke that could explain patient's symptoms (intracranial or subarachnoid hemorrhage, arteriovenous malformation, aneurysm, multiple sclerosis, tumor, abscess or other). Asymptomatic meningiomas are allowed.
  • Patient had a stroke (ischemic or hemorrhagic) with residual deficit within 1 month prior to treatment.
  • Mild stroke, defined as NIH Stroke Scale <2.
  • Patient has received or is expected to receive intravenous rt-PA within 3 hours or intra-arterial rt-PA within 6 hours of stroke onset, according to our institutional standard of care.
  • Receipt of intravenous rt-PA after 3 hours or intra-arterial rt-PA after 6 hours post-stroke onset.
  • Seizure at presentation or within two weeks prior to stroke.
  • Patient is comatose, regardless of etiology (> 4 points on the first three items of the NIHSS).
  • History of intolerance or allergic reaction to any statins (myotoxicity, hepatic dysfunction, rash, etc.)
  • Use of drugs within past 30 days that utilize the cytochrome CYP3A pathway (cyclosporine, itraconazole, ketoconazole, erythromycin, azithromycin, clarithromycin, nefazodone).
  • Use of drugs within past 30 days that increase risk of myotoxicity with statins (gemfibrozil, other fibrates, niacin, amiodarone, verapamil).
  • Baseline major electrolyte disturbances (sodium <125 or >150, potassium <3.0 or >5.5).
  • Recent major trauma (<3 months).
  • Hypothermia (body temperature < 96 degrees Fahrenheit).
  • Baseline hypoxia (defined as oxygen saturation <92% on room air).
  • History of likely or proven systemic viral infection within 30 days.
  • Known HIV infection or use of protease inhibitors.
  • Endocarditis likely as cause of stroke.
  • Mitochondrial disorder likely as cause of stroke.
  • Pregnancy or lactation.
  • History of rhabdomyolysis, myopathy, or other severe muscle disease.
  • History of hepatitis, decompensated liver disease (ascites, bleeding varices or encephalopathy), or liver failure.
  • Liver function tests (ALT, AST) > 2X upper limit of normal.
  • Unstable cardiovascular (includes uncontrolled hypertension), pulmonary, gastrointestinal, hepatic or musculoskeletal disease within one month (30 days) prior to treatment (by reported history).
  • Patient has evidence of congestive heart failure or has history of end-stage cardiovascular disease (e.g. CHF NYHA Class III or IV or unstable angina).
  • Abnormal ECG showing: Hemodynamically significant arrhythmia or frequent PVCs (>5/minute) (controlled atrial arrhythmia will not be an exclusion); evidence of acute myocardial infarction; Mobitz Type II 2nd degree AV block or 3rd degree AV block; ventricular tachycardia or ventricular fibrillation.
  • Significant renal insufficiency, indicated by serum creatinine >2.0 mg/dl.
  • Hypoglycemia (glucose < 60 mg/dl), significant hyperglycemia (glucose > 400 mg/dl) or diabetic ketoacidosis.
  • Any of these hematologic abnormalities: Hb <10 g/dl; WBC <3.0 x 103/mm3; Platelet count <50,000/mm3
  • Received an investigational drug within 30 days.
  • Severe behavioral or social problems that may interfere with the conduct of clinical study procedures.
  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: NCT00243880

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Mitchell Elkind, MD, MS Columbia University
Principal Investigator: Ji Chong, MD Columbia University
  More Information

Publications:
Responsible Party: Mitchell Elkind, Columbia University
ClinicalTrials.gov Identifier: NCT00243880     History of Changes
Other Study ID Numbers: AAAA5855, R01NS049060
Study First Received: October 24, 2005
Last Updated: January 12, 2011
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by Columbia University:
acute ischemic stroke
lovastatin
statin
neuroprotection
SPOTRIAS

Additional relevant MeSH terms:
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Lovastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 11, 2014