Could Early Atorvastatin Offer Anti Inflammatory Effects Upon Brain in Traumatic Head Injury?
Primary Purpose
Traumatic Brain Injury
Status
Completed
Phase
Not Applicable
Locations
Egypt
Study Type
Interventional
Intervention
Atorvastatin
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Traumatic Brain Injury focused on measuring Traumatic brain injury, N-acetyl-aspartate
Eligibility Criteria
Inclusion Criteria:
- adult
- traumatic brain injury mild to moderate
Exclusion Criteria:
- immunotherapey
- diabetic
- previous CNs dysfunction
Sites / Locations
- Emad Zarief Kamel Said
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
statin group
control
Arm Description
will receive atorvastatin for 48 hours
will receive placebo tablets for 48 hours
Outcomes
Primary Outcome Measures
brain magnetic resonance spectroscopy
presence or absence of abnormal metabolites seen by magnetic resonance spectroscopy
Secondary Outcome Measures
ICU stay
days of ICU stay
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04718155
Brief Title
Could Early Atorvastatin Offer Anti Inflammatory Effects Upon Brain in Traumatic Head Injury?
Official Title
Could Early Atorvastatin Offer Anti Inflammatory Effects Upon Brain in Traumatic Head Injury? a Randomized Double-blind Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
April 30, 2022 (Actual)
Study Completion Date
June 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Assiut University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are widely used to reduce levels of low-density lipoprotein-cholesterol. As lipid-lowering drugs, statins exert neuroprotective effects on ischemic stroke. this study will investigate whether the protective effect of statins is mediated by their ability to impact inflammation and oxygen free radical levels in cerebral ischemia/reperfusion injury.
Could Statins affect the neuroinflamation which occurs after traumatic brain injury?
Detailed Description
Traumatic brain injury (TBI) is one of the most common and financially devastating health problems in our society. Once the acute care period has ended, many TBI patients are left with motor, cognitive, or emotional dysfunction as a result of their injury. The treatment of TBI remains largely supportive, directed toward management of cerebral edema and intracranial hypertension via temporizing measures, such as administration of osmotic agents, hyperventilation, and ventricular drainage. None of these interventions have been definitively demonstrated to improve long-term functional outcome. The failure of preclinical therapies to translate into clinical benefit may derive from the heterogeneity of TBI pathology, which includes diffuse axonal injury, cerebral contusion, intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and extra parenchymal hemorrhage. These primary insults are exacerbated by a secondary neuroinflammatory cascade of cerebral hypoperfusion and ischemia, oxidative stress, cerebral edema, and intracranial hypertension. There are a series of reactions following cerebral ischemia/reperfusion, such as inflammation and an increase in free radicals, which may trigger secondary injury in ischemic tissue. Indeed, the inhibition of inflammation reduces tissue damage in ischemia. Thus, understanding the roles of inflammation and free radicals in ischemia/reperfusion injury is therefore of great importance.
3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are widely used to reduce levels of low-density lipoprotein-cholesterol. As lipid-lowering drugs, statins exert neuroprotective effects on ischemic stroke. In this study, teh study will investigate whether the protective effect of statins is mediated by their ability to impact inflammation and oxygen free radical levels in cerebral ischemia/reperfusion injury. Statins have been shown to reduce morbidity in patients who did not have high serum cholesterol or cardiovascular disease but did have evidence of systemic inflammation. Statins have strong efficacy on modulation of inflammatory responses. conditions where statins have been found to have a positive effect on disease progression or mortality are primarily dependent on leucocyte accumulation. Statins may thus promote the timely resolution of the inflammatory response, preventing persistence of inflammation and resultant pathology.
Magnetic resonance spectroscopy (MRS) allows for measurement of metabolites that are undetectable by conventional neuroimaging thereby holding potential to identify traumatic brain injury patients that could benefit from specific neuropsychiatric and cognitive rehabilitation . Brain energy metabolism is altered after TBI due to posttraumatic inflammation and ischemia with mitochondrial dysfunction and loss of neuronal integrity with increased cell membrane turnover. MRS is an MRI technique that can detect nuclei with spins such as 1H, an abundant by-product of cellular respiration and brain tissue metabolites. As a noninvasive and safe technique, MRS is available on clinical MR scanners (1.5 and 3.0 T) without ionizing radiation [15]. This method holds the potential to identify compromised brain metabolism, but evidence after traumatic brain injury is rare .
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury
Keywords
Traumatic brain injury, N-acetyl-aspartate
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
statin group
Arm Type
Active Comparator
Arm Description
will receive atorvastatin for 48 hours
Arm Title
control
Arm Type
Placebo Comparator
Arm Description
will receive placebo tablets for 48 hours
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Intervention Description
will receive 40 mg atrorvastatin 2 days
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
will receive 40 mg placebo 2 days
Primary Outcome Measure Information:
Title
brain magnetic resonance spectroscopy
Description
presence or absence of abnormal metabolites seen by magnetic resonance spectroscopy
Time Frame
first 48 hours
Secondary Outcome Measure Information:
Title
ICU stay
Description
days of ICU stay
Time Frame
first 30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
- adult
traumatic brain injury mild to moderate
Exclusion Criteria:
immunotherapey
diabetic
previous CNs dysfunction
Facility Information:
Facility Name
Emad Zarief Kamel Said
City
Assiut
ZIP/Postal Code
71111
Country
Egypt
12. IPD Sharing Statement
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Could Early Atorvastatin Offer Anti Inflammatory Effects Upon Brain in Traumatic Head Injury?
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