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

February 21, 2024 updated by: University of Arizona

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)

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 Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Other Names:
  • Angiotensin I/II (1-7) acetate
Experimental: 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.
Drug: 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.
Other Names:
  • Angiotensin I/II (1-7) acetate
Placebo Comparator: Placebo
Sterile saline (NaCl) will be delivered as a subcutaneous injection for 21 days.
Drug: Sterile saline
Sterile solution of 0.9% NaCl in water.
Other Names:
  • Sterile sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At 21 days
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.
90 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive functions after Angiotensin (1-7) treatment as measured by the Montreal Cognitive Assessment (MoCA)
Time Frame: 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.
90 days
Function after Angiotensin (1-7) treatment, as measured by the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Time Frame: 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.
90 days
Effects of Angiotensin (1-7) on acute CNS damage biomarker phosphorylated tau (p-tau)
Time Frame: Enrollment to 21 days
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
Time Frame: Enrollment to 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
Time Frame: MRI baseline to 90 days
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
Time Frame: Admission to discharge, average of 5 days
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)
Time Frame: 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.
Admission to discharge, average of 5 days
Change in suicidal ideation and behavior as assessed by the Patient Health Questionnaire (PHQ-9)
Time Frame: 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.
Enrollment to 21 days, enrollment to 90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Arizona

Collaborators

United States Department of Defense

Investigators

  • Principal Investigator: Bellal Joseph, MD, University of Arizona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2024

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

December 19, 2023

First Submitted That Met QC Criteria

February 21, 2024

First Posted (Actual)

February 28, 2024

Study Record Updates

Last Update Posted (Actual)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 21, 2024

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AngT-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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