Effect of Rosuvastatin on Cytokines After Traumatic Brain Injury

Study Overview
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Brief Summary
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The purpose of this study is to determine whether rosuvastatin could alter the immunological response after head injury by modulating TNF-alpha,IL6,IL-1.

Detailed Description
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The head injury is a frequent problem of health, which produces high morbid-mortality. Today is the main cause of death and disability between 18 and 40 years. In addition it originates expensive expenses in health care systems. Head injury produces damage by primary mechanisms related to impact, then by biochemical ways which are activated and they carry to secondary damage. Many studies have been conducted for explaining secondary injury, the majority conclude there is a kind of ischemic lesion related maybe with changes in cerebral flow and metabolism. All these changes are associated to a immunological response. Up to now some drugs are directed to modulate the immunological system, although many of them have been ineffective. Statins o inhibitors of HMG CoA reductase are drugs used in dyslipidemia, frequently for reduction in LDL. Experimental and clinical studies in stroke have shown improvement in outcome. The toxicity related to statin is myopathy and hepatopathy, both with low incidence without fatal cases. Rosuvastatin has been postulated be the most powerful with longest life and toxicity similar to another statins. Many studies have suggested an important immunomodulator effect after statins administration, The investigators have previously demonstrated the possible effect of statin on amnesia and disorientation improvement with patients who suffered a moderated head injury (Glasgow 9-13). The aim of this new study is to analyze the possible immunomodulator role of statins on head injury.

Official Title
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Effect of Rosuvastatin on Immunological Markers After Traumatic Brain Injury: Clinical Randomized Double Blind Study Phase 2

Conditions
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Head Injury

Intervention / Treatment
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* Drug: Rosuvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man or woman > 16 and < 60 years old with HI less 24 hours in progression and Glasgow between < 13 Acceptance of family to participate (first grade) Exclusion Criteria: Previous head injury with severe disability History of neurological or psychiatric disease with severe disability Administration 24 hrs previous of: fibrates, niacin, ciclosporin, azoles, macrolides, inhibitors of protease, nefazodone, verapamil, diltiazem,amiodarone Very poor possibilities for survival Use of Administration of THAM, mannitol, barbiturates, corticosteroids, scavengers of free radicals, inhibitors of lipidic peroxidation, indometacin, calcium antagonist, antagonists of neurotransmitters before randomization isolated lesions in brain stem Allergy to the drug Hepatopathy or myopathy (or) history of this, or clinical data of hepatic disease Management previous in other Hospital Pregnancy

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rosuvastatin<br>20 mg oral during 10 days | Drug: Rosuvastatin<br>* 20 mg oral, for 10 days<br>* Other names: Crestor;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 20 mg vehicle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasmatic levels of cytokines (IL-1B, IL-6, TNF-alfa) (pg/dL) |  | Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional outcome by Disability Rating Scale |  | after 3 months | 
| change of lesions on CT scan |  | 72 hours | 
| Determination of CK, AST, ALT |  | 3rd and 7th day | 
| Amnesia time using GOAT Score |  | in-patient follow-up, after 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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moderate head injury, rosuvastatin, statin, amnesia, orientation