Safety and Efficacy of Angiotensin (1-7) in Persons With Moderate to Severe Traumatic Brain Injury
- Conditions
- Traumatic Brain Injury
- Interventions
- Drug: Sterile saline
- Registration Number
- NCT06282965
- Lead Sponsor
- University of Arizona
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Sterile saline Sterile saline (NaCl) will be delivered as a subcutaneous injection for 21 days. Ang 1-7 100 mcg/kg/day Angiotensin (1-7) 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 Angiotensin (1-7) 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.
- Primary Outcome Measures
Name Time Method Number of participants with adverse events At 21 days 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.
Performance on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 90 days 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.
- Secondary Outcome Measures
Name Time Method Incidence and duration of delirium as assessed by the Confusion Assessment Method (CAM) Admission to discharge, average of 5 days The Confusion Assessment Method (CAM) is used to diagnose delirium using an algorithm based on the following features:
1. Acute onset and fluctuating course.
2. Inattention.
3. Disorganized thinking.
4. Altered level of consciousness.Function after Angiotensin (1-7) treatment, as measured by the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) 90 days 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.
Effects of Angiotensin (1-7) on acute CNS damage biomarker phosphorylated tau (p-tau) Enrollment to 21 days Change in phosphorylated tau (p-tau), a biomarker which can predict cognitive decline, cognitive impairment, and dementia.
Effects of Angiotensin (1-7) on CNS damage biomarker phosphorylated tau (p-tau) after 90 days Enrollment to 90 days Change in phosphorylated tau (p-tau), a biomarker which can predict cognitive decline, cognitive impairment, and dementia.
Cognitive functions after Angiotensin (1-7) treatment as measured by the Montreal Cognitive Assessment (MoCA) 90 days 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.
Effects of Angiotensin (1-7) on brain white matter integrity MRI baseline to 90 days Assessment of difference in white matter integrity calculated from MR images.
Effects of Angiotensin (1-7) on length of hospital stay Admission to discharge, average of 5 days Length of stay will be calculated as the difference between the admission and discharge dates.
Change in suicidal ideation and behavior as assessed by the Patient Health Questionnaire (PHQ-9) Enrollment to 21 days, enrollment to 90 days 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.
Trial Locations
- Locations (1)
University of Arizona
🇺🇸Tucson, Arizona, United States