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

NCT00243880 | Completed Phase 1 DMC

• 2 other identifiers: AAAA5855R01NS049060
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Stroke

Keywords

acute ischemic stroke; lovastatin; statin; neuroprotection; SPOTRIAS

Outcome Measures

Primary Outcomes (1)

• safety through 30 days defined as absence of liver or muscle-related toxicity on days 1, 2, 3, 5, 7, and 30.

  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

  30 days

Secondary Outcomes (1)

• pharmacokinetic measurements made on days 1, 3, 4, and 5.

  5 days

Study Arms (1)

lovastatin

EXPERIMENTAL

lovastatin at escalating dosages: 1 mg/kg/day, 3 mg/kg/day, 6 mg/kg/day, 8 mg/kg/day, 10 mg/kg/day

Drug: lovastatin

Interventions

lovastatin DRUG

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.

Also known as: Mevacor

lovastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (2)

• Elkind MS, Sacco RL, MacArthur RB, Fink DJ, Peerschke E, Andrews H, Neils G, Stillman J, Corporan T, Leifer D, Cheung K. The Neuroprotection with Statin Therapy for Acute Recovery Trial (NeuSTART): an adaptive design phase I dose-escalation study of high-dose lovastatin in acute ischemic stroke. Int J Stroke. 2008 Aug;3(3):210-8. doi: 10.1111/j.1747-4949.2008.00200.x.

  PMID: 18705902 BACKGROUND

• Elkind MS, Sacco RL, Macarthur RB, Peerschke E, Neils G, Andrews H, Stillman J, Corporan T, Leifer D, Liu R, Cheung K. High-dose lovastatin for acute ischemic stroke: results of the phase I dose escalation neuroprotection with statin therapy for acute recovery trial (NeuSTART). Cerebrovasc Dis. 2009;28(3):266-75. doi: 10.1159/000228709. Epub 2009 Jul 16.

  PMID: 19609078 RESULT

MeSH Terms

Conditions

Stroke; Ischemic Stroke

Interventions

Lovastatin

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Mitchell Elkind, MD, MS

  Columbia University

  PRINCIPAL INVESTIGATOR

• Ji Chong, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology and Epidemiology (in the Sergievsy Center)

Study Record Dates

• First Submitted: October 24, 2005
• First Posted: October 25, 2005
• Study Start: September 1, 2005
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: May 9, 2016

Record last verified: 2016-05

Locations

US (1)