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

November 16, 2023 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

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

672

Phase

  • 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 Backup

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94110
        • University of California, San Francisco
        • Principal Investigator:
          • Michael Huang, MD
        • 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:

  1. Adults (18-65 years of age inclusive)
  2. Presents to an enrollment site within 12 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. Post-resuscitation Glasgow Coma Scale (GCS) of between 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 the participant is 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 or need for sedation
  8. Participants/legally authorized representative (LAR) willing and able to provide informed consent
  9. Participants or legally authorized representative able to read, speak, understand English or Spanish including the informed consent form (ICF)
  10. Willingness and ability to comply with all study procedures, treatment and follow-up
  11. Participants identified by site investigator as a good candidate for study participation

Exclusion Criteria:

  1. Post-resuscitation GCS <9
  2. Isolated epidural hematoma
  3. 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
  4. Current enrollment in another interventional study
  5. Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6 months
  6. Current incarceration
  7. 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
  8. Hypersensitivity or intolerance to investigational products or the investigational products respective classes
  9. Renal dysfunction (Creatinine Clearance (CrCl) or Estimate Glomerular Filtration Rate (eGFR) <60 mL/minute/1.73 m2)
  10. Hepatic dysfunction (Alanine Transaminase (ALT)/Aspartate Transaminase (AST)) >3 times upper limit of normal lab value)
  11. Persistent hypotension, more than 30 minutes (Systolic Blood Pressure (SBP) <90 mmHg and Diastolic Blood Pressure (DBP) <60 mmHg)
  12. Inability to swallow investigational product capsule
  13. Low likelihood of follow up or study compliance, or any other reason, in the opinion of the 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
Intervention / Treatment
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

Outcome Measure
Measure Description
Time Frame
Change in Glasgow Outcome Scale-Extended (GOSE-TBI only)
Time Frame: 2 weeks to 3 months postinjury
Functional impairment due only to the TBI will be measured using the GOSE Scale. 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

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

University of California, San Francisco

Collaborators

United States Department of Defense

Investigators

  • 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 (Estimated)

March 29, 2024

Primary Completion (Estimated)

February 29, 2028

Study Completion (Estimated)

February 28, 2029

Study Registration Dates

First Submitted

April 12, 2023

First Submitted That Met QC Criteria

April 12, 2023

First Posted (Actual)

April 24, 2023

Study Record Updates

Last Update Posted (Estimated)

November 20, 2023

Last Update Submitted That Met QC Criteria

November 16, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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.

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