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)
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- University of Arizona
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- Number of participants with adverse events
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Masking Description
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.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •Severe TBI will be defined as loss of consciousness \> 24 hours and GCS ≤
- •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.
Arms & Interventions
Ang 1-7 100 mcg/kg/day
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.
Intervention: Angiotensin (1-7) (Drug)
Ang 1-7 200 mcg/kg/day
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.
Intervention: Angiotensin (1-7) (Drug)
Placebo
Sterile saline (NaCl) will be delivered as a subcutaneous injection for 21 days.
Intervention: Sterile saline (Drug)
Outcomes
Primary Outcomes
Number of participants with adverse events
Time Frame: 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)
Time Frame: 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 Outcomes
- Incidence and duration of delirium as assessed by the Confusion Assessment Method (CAM)(Admission to discharge, average of 5 days)
- Function after Angiotensin (1-7) treatment, as measured by the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)(90 days)
- Effects of Angiotensin (1-7) on acute CNS damage biomarker phosphorylated tau (p-tau)(Enrollment to 21 days)
- Effects of Angiotensin (1-7) on CNS damage biomarker phosphorylated tau (p-tau) after 90 days(Enrollment to 90 days)
- Cognitive functions after Angiotensin (1-7) treatment as measured by the Montreal Cognitive Assessment (MoCA)(90 days)
- Effects of Angiotensin (1-7) on brain white matter integrity(MRI baseline to 90 days)
- Effects of Angiotensin (1-7) on length of hospital stay(Admission to discharge, average of 5 days)
- Change in suicidal ideation and behavior as assessed by the Patient Health Questionnaire (PHQ-9)(Enrollment to 21 days, enrollment to 90 days)