Multi-Arm Multi-Stage Adaptive Platform Trial (APT) for the Acute Treatment of Traumatic Brain Injury (APT-TBI-01)

December 18, 2025 updated by: University of California, San Francisco
The purpose of this study is to determine if experimental drug treatment improves recovery after TBI as compared to a control (placebo) group. Changes in recovery will be measured throughout the study. The study drugs listed below are approved by the U.S. Food and Drug Administration (FDA) but are being used "off-label" in this study. This means that the drugs are not currently approved to treat TBI.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
672

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94110
        • University of California, San Francisco
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Atrium Health Wake Forest Baptist
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Vanderbilt University Medical Center
    • Texas
      • Austin, Texas, United States, 78712
        • The University of Texas at Austin
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • Houston, Texas, United States, 77030
        • UTHealth Houston
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
    • Washington
      • Seattle, Washington, United States, 98104
        • University of Washington
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • UW Health University Hospital
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adults (18-65 years of age, inclusive)
  2. Presents to a participating enrollment site and is able to receive first dose within 24 hours of non-penetrating head injury warranting clinical evaluation with a non-contrast head CT based on American College of Emergency Physicians (ACEP) Centers for Disease Control and Prevention (CDC) clinical policy for TBI imaging.
  3. Closest, prior to Randomization Glasgow Coma Scale (GCS) score of 9 to 15
  4. Acute trauma-related neuroimaging abnormality (subarachnoid hemorrhage, contusion, subdural hematoma, petechial hemorrhage, intraventricular hemorrhage) on cranial CT (CT+)
  5. Initial Glial Fibrillary Acidic Protein (GFAP) blood level >100 pg/ml ≤ 15,000 pg/ml determined using a for Research Use Only (RUO) assay(s) or an Investigation Use Only (IUO) assay(s)
  6. Persons of childbearing potential (i.e., those not postmenopausal or surgically sterile) may participate provided that they are using adequate birth control methods for the duration of investigational product administration (see manual of procedures for adequate birth control methods)
  7. Participants able to undergo Magnetic Resonance Imaging (MRI) scans, no contraindications
  8. Participants or legally authorized representative (LAR) willing and able to provide informed consent
  9. Participants or LAR able to read, speak, and understand English or Spanish (participating site dependent, where available), including the informed consent form (ICF)
  10. Willingness and ability to comply with all study procedures, treatment, and follow-up

Exclusion Criteria:

  1. Isolated epidural hematoma
  2. Pre-existing conditions including disabling developmental, neurologic, psychiatric, medical disorder that continues to produce functional disability up to the time of injury; or imminent death based on clinical judgement
  3. Current enrollment in another interventional study
  4. Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6 months
  5. Current incarceration or in custody
  6. Currently prescribed one of the investigational products (or other drugs in the same class) prior to injury; or contra-indicated or as listed in the appendices
  7. Hypersensitivity or intolerance to investigational products or the investigational products' respective classes
  8. Renal dysfunction (Creatinine Clearance (CrCl) or estimated Glomerular Filtration Rate (eGFR) (<60 mL/minute/1.73 m2)
  9. Acute liver disease or hepatic dysfunction (ALT/AST >3 times upper limit of normal lab value)
  10. Hemodynamic instability, per participating site physician investigator clinical judgment
  11. Inability to swallow investigational product capsule
  12. Unable or unwilling to consume animal byproducts, has a gelatin allergy, and/or religious beliefs that do not permit consuming gelatin
  13. Intolerance to small amounts of lactose (less than ½ teaspoonful) daily
  14. Low likelihood of follow up or study compliance, or any other reason, in the opinion of the participating site investigator, the participants should not participate 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: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Intervention 1: Atorvastatin calcium (ATOR)
By Mouth (PO) Twice a day (BID) 80 mg/day, with no loading dose, for 28 days
Drug: Atorvastatin Calcium
Capsule, 80 mg/day, with no loading dose, for 28 days
Other Names:
  • ATOR
Active Comparator: Intervention 2: Minocycline hydrochloride (MINO)
By Mouth (PO) Twice a day (BID) 200 mg loading dose on Day 1, then 100 mg twice daily for 6 days, then placebo twice daily for 21 days
Drug: Minocycline Hydrochloride
Capsule, 200 mg loading dose on Day 1, then 100 mg twice daily for 6 days, then placebo twice daily for 21 days
Other Names:
  • MINO
Active Comparator: Intervention 3: Candesartan cilexetil (CAND)
By Mouth (PO) Twice a day (BID) 8 mg once on Day 1, then 16 mg daily for 27 days
Drug: Candesartan Cilexetil
Capsule, 8 mg once on Day 1, then 16 mg daily for 27 days
Other Names:
  • CAND
Placebo Comparator: Matching Placebo
By Mouth (PO) Twice a day (BID) 2 capsules 2x/day
Drug: Placebo
Capsule, 2x/day for 28 days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Glasgow Outcome Scale-Extended (GOSE 2-Way)
Time Frame: 2 weeks to 3 months postinjury
Functional impairment due only to the TBI will be measured using the GOSE Scale-Extended (GOSE 2-Ways). The score ranges from 1-8, with higher scores indicating better recovery. Change will be measured from Week 2 to Month 3 postinjury and compared to placebo.
2 weeks to 3 months postinjury

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Blood-based biomarkers (Neurofilament light chain)
Time Frame: Week 2
Neurofilament light chain (NfL) levels postinjury in participants with TBI will be measured and compared to placebo
Week 2
Blood-based biomarker (GFAP)
Time Frame: Week 2
GFAP levels postinjury in participants with TBI as compared to placebo
Week 2
Imaging biomarkers
Time Frame: 2 weeks to 3 months postinjury
Comparison of MRI diffusion tensor imaging (DTI) Axial Diffusivity (AD) measure using the average of 4 long association/projections tracts: (i) Anterior Limb of Internal Capsule (ALIC); (ii) External Capsule (EC); (iii) Superior Corona Radiata (SCR); and (iv) Superior Longitudinal Fasciculus (SLF). Change will be measured from 2 Weeks to 3 Months postinjury.
2 weeks to 3 months postinjury
Post-TBI cognitive outcome (BTACT)
Time Frame: Day 3 to Week 4 postinjury
Neurocognitive impairment due to TBI will be measured using the Brief Test of Adult Cognition by Telephone (BTACT). Change will be measured by composite z-score from Day 3 to Week 4 postinjury
Day 3 to Week 4 postinjury
Post-TBI symptom outcome (Rivermead)
Time Frame: Day 3 to Week 4
Post-concussive symptoms due to TBI as measured by the change in Rivermead Post Concussion Symptoms Questionnaire (RPQ) Total score (0-64) from Day 3 to Week 4. Higher scores indicate more severe symptoms
Day 3 to Week 4

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, San Francisco

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
United States Department of Defense

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Geoffrey Manley, MD PhD, University of California, San Francisco

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.

Helpful Links

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 31, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 12, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 12, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 24, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 22, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APT-TBI-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be made available through the Federal Interagency TBI Research (FITBIR) Database.

IPD Sharing Time Frame

Shared scientific data will be made accessible as soon as possible, and no later than the time of an associated publication, or the end of performance period, whichever comes first.

IPD Sharing Access Criteria

FITBIR qualified investigators will be provided access

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings