Clinical trial NCT06282965: Safety and Efficacy of Angiotensin (1-7) in Persons With Moderate to Severe Traumatic Brain Injury
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Traumatic Brain Injury
Keywords: renin angiotensin system
cognition
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2024-02-28
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: At 21 days
measure: Performance on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)
timeFrame: 90 days
Secondary outcomes:
measure: Cognitive functions after Angiotensin (1-7) treatment as measured by the Montreal Cognitive Assessment (MoCA)
timeFrame: 90 days
measure: Function after Angiotensin (1-7) treatment, as measured by the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
timeFrame: 90 days
measure: Effects of Angiotensin (1-7) on acute CNS damage biomarker phosphorylated tau (p-tau)
timeFrame: Enrollment to 21 days
measure: Effects of Angiotensin (1-7) on CNS damage biomarker phosphorylated tau (p-tau) after 90 days
timeFrame: Enrollment to 90 days
measure: Effects of Angiotensin (1-7) on brain white matter integrity
timeFrame: MRI baseline to 90 days
measure: Effects of Angiotensin (1-7) on length of hospital stay
timeFrame: Admission to discharge, average of 5 days
measure: Incidence and duration of delirium as assessed by the Confusion Assessment Method (CAM)
timeFrame: Admission to discharge, average of 5 days
measure: Change in suicidal ideation and behavior as assessed by the Patient Health Questionnaire (PHQ-9)
timeFrame: Enrollment to 21 days, enrollment to 90 days
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
Study officials:
affiliation: University of Arizona
name: Bellal Joseph, MD
role: PRINCIPAL_INVESTIGATOR
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