Anti-inflammatory Effect of MgSO₄ in Patients With Moderate Traumatic Brain Injury by Measurming Nucleotide-binding Oligomerization Domain-Like Receptor Pyrin Domain-containing 3 (NLRP3) Inflammasome-a Multiprotein Complex
Anti-Inflammatory Effect of Magnesium Sulfate on the Outcomes of Patients With Moderate Traumatic Brain Injury.
연구 개요
상세 설명
Traumatic brain injury (TBI) remains a leading cause of mortality and long-term disability worldwide, disrupting both individual lives and healthcare systems. The pathophysiology of TBI is characterized by a biphasic process. The primary injury occurs at the moment of impact, resulting in immediate mechanical tissue disruption. This is followed by a complex cascade of cellular and molecular changes known as secondary brain injury, which develops hours to days later.
A cornerstone of this secondary injury pathway is neuroinflammation, driven by the activation of resident microglia and the infiltration of peripheral immune cells. Central to this inflammatory response is the assembly and activation of the Nucleotide-binding oligomerization domain-Like Receptor Pyrin domain-containing 3 (NLRP3) inflammasome-a multiprotein complex that triggers the maturation and release of potent pro-inflammatory cytokines, specifically interleukin-1β (IL-1β) and interleukin-18 (IL-18), accelerating neuronal apoptosis and blood-brain barrier dysfunction.
Magnesium sulfate (MgSO₄) has emerged as a promising neuroprotective candidate due to its multifaceted mechanism of action. Primarily, magnesium acts as a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, thereby mitigating glutamate-mediated excitotoxicity. Emerging molecular evidence further indicates that magnesium exerts potent anti-inflammatory effects by downregulating nuclear factor kappa B (NF-κB) activation and directly inhibiting the assembly of the NLRP3 inflammasome. Consequently, evaluating the clinical and molecular efficacy of MgSO₄ in TBI patients could offer a viable therapeutic pathway to suppress secondary neuroinflammation and optimize neurological recovery.
NLRP3 Inflammasome is a multiprotein complex consisting of three core components:
- Sensor (NLRP3)
- Adaptor (ASC)
- Effector (Caspase-1)
Its activation is regulated by a two-signal framework:
- Priming (Signal 1): Activates the nuclear factor kappa B(NF-κB) pathway to produce baseline NLRP3 components and inactive proteins (Pro-IL-1β, P ro-IL-18 andPro-IL-6).
- Activation (Signal 2): Triggered by cellular stress signals (such as Ca 2+ influx, K efflux, and mitochondrial distress).
Active Caspase-1 processes cytokines into their potent active forms and triggers a inflammatory cell death.
Magnesium sulfate (MgSO₄) has emerged as a promising neuroprotective candidate.
Magnesium sulfate exerts potent anti-inflammatory effects that can inhibit NLRP3 Inflammasome activation through 4 mechanisms:
- downregulating nuclear factor kappa B (NF-κB) activation and directly inhibiting the assembly of the NLRP3 inflammasome
- preventing extracellular Ca2+ influx and intracellular release
- Reducing K Efflux
- Preserving Mitochondrial Integrity
연구 유형
등록 (추정된)
단계
- 4단계
연락처 및 위치
연구 연락처
- 이름: Ehab Samir, Assistant lecturer
- 전화번호: +201003078676
- 이메일: hobasamir12@gmail.com
연구 연락처 백업
- 이름: Ghada Abolfadl, Prof.
- 전화번호: +201005802086
- 이메일: ghadafadl@aun.edu.eg
참여기준
자격 기준
공부할 수 있는 나이
- 성인
건강한 자원 봉사자를 받아들입니다
설명
Inclusion Criteria:
- Male and female patients aged 18 to 60 years.
- Sustained a closed head trauma with the study drug infusion initiated within 8 hours of the injury.
- TBI confirmed by history and clinical examination.
- Patients with moderate (GCS = 9-12) traumatic brain injury.
- Evidence of TBI confirmed by abnormalities consistent with trauma on CT scan upon admission (diffuse injury II-IV, evacuated and non-evacuated mass lesion, Marshall's CT Classification ).
- Hemodynamic stability at the time of enrollment.
Exclusion Criteria:
- Patient Refusal
- Prolonged and/or uncorrectable hypoxia (PaO₂ < 60 mmHg) or persistent hypotension (systolic blood pressure < 90 mmHg) at the time of randomization.
- Cardiopulmonary arrest.
- Concomitant spinal cord injury.
- Pregnant or lactating females.
- Penetrating head injury.
- Associated other extra-cranial trauma or systemic polytrauma.
- Undergoing surgical interventions during the study.
- Pre-existing severe cardiac arrhythmia, heart block, or significant myocardial damage (documented on ECG).
- Known history of chronic renal failure or abnormal baseline renal function.
- Known hypersensitivity or allergic reaction to magnesium sulfate.
- Patients on chronic steroid therapy.
BMI>35 kg/m2.
-
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 다른
- 할당: 무작위
- 중재 모델: 요인 할당
- 마스킹: 삼루타
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Group (A): Will receive intravenous magnesium sulfate MgSO₄.
32 patients will receive
|
evaluate the biochemical efficacy of Magnesium Sulfate (MgSO₄) as an anti-inflammatory therapeutic agent in patients suffering from moderate traumatic brain injury (TBI)
|
|
실험적: Group (B): Will receive intravenous normal saline as a placebo.
32 patients Will receive intravenous normal saline as a placebo.
|
evaluate the biochemical efficacy of Magnesium Sulfate (MgSO₄) as an anti-inflammatory therapeutic agent in patients suffering from moderate traumatic brain injury (TBI)
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Measured by the change in serum concentrations of the NLRP3 inflammasome complex
기간: Measured by the change in serum concentrations of the NLRP3 inflammasome complex components from baseline (T₀) to 48 hours post-intervention (T₄₈), quantified via Enzyme-Linked Immunosorbent Assay (ELISA)
|
Molecular Anti-inflammatory Response: Measured by the change in serum concentrations of the NLRP3 inflammasome complex components from baseline (T₀) to 48 hours post-intervention (T₄₈), quantified via Enzyme-Linked Immunosorbent Assay (ELISA)
|
Measured by the change in serum concentrations of the NLRP3 inflammasome complex components from baseline (T₀) to 48 hours post-intervention (T₄₈), quantified via Enzyme-Linked Immunosorbent Assay (ELISA)
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Glasgow Coma Scale (GCS) score
기간: day 7 post-injury and one month
|
Glasgow Coma Scale (GCS) score
|
day 7 post-injury and one month
|
|
Incidence of hypermagnesemia-related toxicity or drug-related adverse events
기간: 48 hours
|
measurement of magnesium sulfate on admission and post intervention
|
48 hours
|
|
ESR, CRP and serum Magnesium levels on admission (T₀) and 48 hours post-intervention (T₄₈)
기간: 48 hours
|
ESR, CRP and serum Magnesium levels on admission (T₀) and 48 hours post-intervention (T₄₈)
|
48 hours
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- effect of MgSO₄ in TBI
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .