Could Early Atorvastatin Offer Anti Inflammatory Effects Upon Brain in Traumatic Head Injury?

NCT ID: NCT04718155

Last Updated: 2022-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2022-06-01

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 .

Conditions

Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

statin group

will receive atorvastatin for 48 hours

Group Type: ACTIVE_COMPARATOR

Atorvastatin

Intervention Type: DRUG

will receive 40 mg atrorvastatin 2 days

control

will receive placebo tablets for 48 hours

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

will receive 40 mg placebo 2 days

Interventions

Atorvastatin

will receive 40 mg atrorvastatin 2 days

Intervention Type: DRUG

placebo

will receive 40 mg placebo 2 days

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• adult

• traumatic brain injury mild to moderate

Exclusion Criteria

• immunotherapey
• diabetic
• previous CNs dysfunction

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Emad Zarief , MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Emad Zarief Kamel Said

Asyut, , Egypt

Countries

Egypt

Other Identifiers

IRB5566000

Identifier Type: -

Identifier Source: org_study_id