Safety and Efficacy of Angiotensin (1-7) in Persons With Moderate to Severe Traumatic Brain Injury

Официальное название

A Randomized, Double-blind, Placebo Controlled Study of the Safety and Efficacy of Angiotensin (1-7) in Persons With Moderate to Severe Traumatic Brain Injury (TBI)

Обзор

The goal of this clinical trial is to test the safety of the drug Angiotensin (1-7) and learn whether it works well as a treatment in people who have suffered a moderate to severe traumatic brain injury (TBI). The main questions this trial aims to answer are: * Is Angiotensin (1-7) safe? * Does Angiotensin (1-7) improve mental functioning and reduce physical signs of brain damage in people who have suffered a moderate to severe TBI? Participants will: * Complete 21 days of study treatment consisting of a once-daily injection. * Provide blood samples. * Undergo two magnetic resonance imaging (MRI) scans of the brain. * Complete specific tasks and questionnaires that allow researchers to evaluate the participant's brain and psychological functioning. Researchers will compare three groups: two groups that receive different doses of Angiotensin (1-7) and one group that receives a look-alike treatment with no active drug. This will allow researchers to see if the drug has any negative effects and whether it improves mental functioning and physical signs of brain damage after a TBI.

Вмешательства

• Препарат Angiotensin (1-7)
  The drug will be dissolved in 0.9% USP/NF grade sterile for injection saline (NaCl) and prepared in a concentration that aligns with the participant's weight.
• Препарат Sterile saline
  Sterile solution of 0.9% NaCl in water.

Первичные конечные точки

• Number of participants with adverse events [Срок оценки: At 21 days]
• Performance on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) [Срок оценки: 90 days]

Вторичные конечные точки (8)

• Cognitive functions after Angiotensin (1-7) treatment as measured by the Montreal Cognitive Assessment (MoCA) [Срок оценки: 90 days]
• Function after Angiotensin (1-7) treatment, as measured by the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) [Срок оценки: 90 days]
• Effects of Angiotensin (1-7) on acute CNS damage biomarker phosphorylated tau (p-tau) [Срок оценки: Enrollment to 21 days]
• Effects of Angiotensin (1-7) on CNS damage biomarker phosphorylated tau (p-tau) after 90 days [Срок оценки: Enrollment to 90 days]
• Effects of Angiotensin (1-7) on brain white matter integrity [Срок оценки: MRI baseline to 90 days]
• Effects of Angiotensin (1-7) on length of hospital stay [Срок оценки: Admission to discharge, average of 5 days]
• Incidence and duration of delirium as assessed by the Confusion Assessment Method (CAM) [Срок оценки: Admission to discharge, average of 5 days]
• Change in suicidal ideation and behavior as assessed by the Patient Health Questionnaire (PHQ-9) [Срок оценки: Enrollment to 21 days, enrollment to 90 days]

Критерии участия

Критерии включения

• Participant or representative willing to provide informed consent.
• Age 18 years or older at time of enrollment.
• Traumatically induced head injury resulting from insult to head from an external force.
• Clinical diagnosis of acute intracranial lesion based on neuroradiologist report. CT scan and report must be available.
• Moderate or severe traumatic brain injury (TBI) defined as Glasgow Coma Scale (GCS) score on trauma presentation of 12 or less. In general: Moderate TBI will be defined as loss of consciousness between 30 minutes and 24 hours and GCS between 9 and 12. Severe TBI will be defined as loss of consciousness > 24 hours and GCS ≤ 9.
• Enrollment within 48 hours of TBI.

Критерии исключения

• Time of injury cannot be determined.
• Neurosurgery within the last 30 days.
• History of neurodegenerative disease or disorder including dementia, Parkinson's disease, multiple sclerosis, seizure disorder, or brain tumors that would impact cognitive testing.
• Contraindication to having an MRI.
• Pregnant or lactating female.
• Female of childbearing potential or sexually active male who is not willing to use an acceptable method of birth control for the treatment period and 7 days after the last dose of the study drug.
• Participation in another clinical study involving investigational product within 30 days prior to study enrollment.
• If in the opinion of the investigator, candidate is unsuitable for participation in the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Arizona — Tucson

Публикации

• Wang KK, Yang Z, Zhu T, Shi Y, Rubenstein R, Tyndall JA, Manley GT. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn. 2018 Feb;18(2):165-180. doi: 10.1080/14737159.2018.1428089. Epub 2018 Jan 23. PMID 29338452
• Khellaf A, Khan DZ, Helmy A. Recent advances in traumatic brain injury. J Neurol. 2019 Nov;266(11):2878-2889. doi: 10.1007/s00415-019-09541-4. Epub 2019 Sep 28. PMID 31563989
• McGinn MJ, Povlishock JT. Pathophysiology of Traumatic Brain Injury. Neurosurg Clin N Am. 2016 Oct;27(4):397-407. doi: 10.1016/j.nec.2016.06.002. Epub 2016 Aug 10. PMID 27637392
• Povlishock JT. The classification of traumatic brain injury (TBI) for targeted therapies. J Neurotrauma. 2008 Jul;25(7):717-8. doi: 10.1089/neu.2008.9964. No abstract available. PMID 18627251
• Kelley BJ, Lifshitz J, Povlishock JT. Neuroinflammatory responses after experimental diffuse traumatic brain injury. J Neuropathol Exp Neurol. 2007 Nov;66(11):989-1001. doi: 10.1097/NEN.0b013e3181588245. PMID 17984681
• Hellmich HL, Capra B, Eidson K, Garcia J, Kennedy D, Uchida T, Parsley M, Cowart J, DeWitt DS, Prough DS. Dose-dependent neuronal injury after traumatic brain injury. Brain Res. 2005 May 24;1044(2):144-54. doi: 10.1016/j.brainres.2005.02.054. Epub 2005 Apr 13. PMID 15885213
• Woodcock T, Morganti-Kossmann MC. The role of markers of inflammation in traumatic brain injury. Front Neurol. 2013 Mar 4;4:18. doi: 10.3389/fneur.2013.00018. eCollection 2013. PMID 23459929
• Israelsson C, Kylberg A, Bengtsson H, Hillered L, Ebendal T. Interacting chemokine signals regulate dendritic cells in acute brain injury. PLoS One. 2014 Aug 25;9(8):e104754. doi: 10.1371/journal.pone.0104754. eCollection 2014. PMID 25153123

Идентификаторы

NCT: NCT06282965 · AngT-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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