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| Name | Class |
|---|---|
| United States Department of Defense | FED |
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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:
Participants will:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ang 1-7 100 mcg/kg/day | Experimental | Angiotensin I/II (1-7) acetate will be delivered as a subcutaneous injection at a dose of 100 micrograms per kilogram per day for 21 days. |
|
| Ang 1-7 200 mcg/kg/day | Experimental | Angiotensin I/II (1-7) acetate will be delivered as a subcutaneous injection at a dose of 200 micrograms per kilogram per day for 21 days. |
|
| Placebo | Placebo Comparator | Sterile saline (NaCl) will be delivered as a subcutaneous injection for 21 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Angiotensin (1-7) | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with adverse events | The number of participants with adverse events in each group will be compared in order to determine whether Angiotensin (1-7) is significantly associated with the occurrence of adverse events. | At 21 days |
| Performance on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) | The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) is a brief neuropsychological assessment consisting of eleven tasks. It is used to assess cognitive function. Errors in each task are summed for a total score ranging from 0 to 70. Higher scores represent greater cognitive dysfunction, with a score of 0 representing the least impairment and a score of 70 representing the greatest impairment. | 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive functions after Angiotensin (1-7) treatment as measured by the Montreal Cognitive Assessment (MoCA) | Difference in performance for the treatment groups compared to controls on the Montreal Cognitive Assessment (MoCA). The range of possible scores is 0-30, with scores of 26 and above being considered normal. | 90 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Clinical Research Coordinator | Contact | (520) 237-6845 | traumaresearch@arizona.edu |
| Name | Affiliation | Role |
|---|---|---|
| Bellal Joseph, MD | University of Arizona | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arizona | Recruiting | Tucson | Arizona | 85724 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29338452 | Background | 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. | |
| 31563989 | Background | 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. |
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| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C118790 | angiotensin I (1-7) |
| D000085 | Acetates |
| ID | Term |
|---|---|
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
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Investigators, study site staff, participants, and caregivers will be unaware of the participant treatment assignments for the duration of the study. The pharmacist will prepare the study treatment and will be unmasked.
|
| Sterile saline | Drug | Sterile solution of 0.9% NaCl in water. |
|
|
| Function after Angiotensin (1-7) treatment, as measured by the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) |
Differences between the treatment groups and controls on the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL), a 23-item inventory to assess daily functioning by asking about the participant's performance of multiple activities in the past four weeks. Scores range from 0 to 78, with 0 indicating the greatest disability. |
| 90 days |
| Effects of Angiotensin (1-7) on acute CNS damage biomarker phosphorylated tau (p-tau) | Change in phosphorylated tau (p-tau), a biomarker which can predict cognitive decline, cognitive impairment, and dementia. | Enrollment to 21 days |
| Effects of Angiotensin (1-7) on CNS damage biomarker phosphorylated tau (p-tau) after 90 days | Change in phosphorylated tau (p-tau), a biomarker which can predict cognitive decline, cognitive impairment, and dementia. | Enrollment to 90 days |
| Effects of Angiotensin (1-7) on brain white matter integrity | Assessment of difference in white matter integrity calculated from MR images. | MRI baseline to 90 days |
| Effects of Angiotensin (1-7) on length of hospital stay | Length of stay will be calculated as the difference between the admission and discharge dates. | Admission to discharge, average of 5 days |
| Incidence and duration of delirium as assessed by the Confusion Assessment Method (CAM) | The Confusion Assessment Method (CAM) is used to diagnose delirium using an algorithm based on the following features:
| Admission to discharge, average of 5 days |
| Change in suicidal ideation and behavior as assessed by the Patient Health Questionnaire (PHQ-9) | The Patient Health Questionnaire (PHQ-9) is a brief questionnaire used to assess the severity of symptoms of depression. The range of possible scores is 0-27, with a higher score indicating greater depression severity. | Enrollment to 21 days, enrollment to 90 days |
| 27637392 | Background | 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. |
| 18627251 | Background | 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. |
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| 23459929 | Background | 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. |
| 25153123 | Background | 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. |
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| 16904973 | Background | Ramlawi B, Rudolph JL, Mieno S, Feng J, Boodhwani M, Khabbaz K, Levkoff SE, Marcantonio ER, Bianchi C, Sellke FW. C-Reactive protein and inflammatory response associated to neurocognitive decline following cardiac surgery. Surgery. 2006 Aug;140(2):221-6. doi: 10.1016/j.surg.2006.03.007. |
| 17703127 | Background | Raizada MK, Ferreira AJ. ACE2: a new target for cardiovascular disease therapeutics. J Cardiovasc Pharmacol. 2007 Aug;50(2):112-9. doi: 10.1097/FJC.0b013e3180986219. |
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| D006259 |
| Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D005227 |
| Fatty Acids |
| D008055 | Lipids |