Traumatic Brain InjuryPhase 2APT-TBI-01NCT05826912
Multi-Arm Multi-Stage Adaptive Platform Trial (APT) for the Acute Treatment of Traumatic Brain Injury
A Phase 2 study testing Atorvastatin Calcium, Minocycline Hydrochloride and Candesartan Cilexetil in people with Traumatic Brain Injury, run by University of California, San Francisco at 18 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Atorvastatin Calcium, Minocycline Hydrochloride and Candesartan Cilexetil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 672 participants
- Where
- 18 sitesUnited States
- Study dates
- 1 Aug 2024to 31 Aug 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (18-65 years of age, inclusive)
- 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.
- Closest, prior to Randomization Glasgow Coma Scale (GCS) score of 9 to 15
- Acute trauma-related neuroimaging abnormality (subarachnoid hemorrhage, contusion, subdural hematoma, petechial hemorrhage, intraventricular hemorrhage) on cranial CT (CT+)
- 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)
- 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)
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- Participants able to undergo Magnetic Resonance Imaging (MRI) scans, no contraindications
- Participants or legally authorized representative (LAR) willing and able to provide informed consent
- Participants or LAR able to read, speak, and understand English or Spanish (participating site dependent, where available), including the informed consent form (ICF)
- Willingness and ability to comply with all study procedures, treatment, and follow-up
Who cannot join
- Isolated epidural hematoma
- 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
- Current enrollment in another interventional study
- Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6 months
- Current incarceration or in custody
- 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
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- Hypersensitivity or intolerance to investigational products or the investigational products' respective classes
- Renal dysfunction (Creatinine Clearance (CrCl) or estimated Glomerular Filtration Rate (eGFR) (<60 mL/minute/1.73 m2)
- Acute liver disease or hepatic dysfunction (ALT/AST >3 times upper limit of normal lab value)
- Hemodynamic instability, per participating site physician investigator clinical judgment
- Inability to swallow investigational product capsule
- Unable or unwilling to consume animal byproducts, has a gelatin allergy, and/or religious beliefs that do not permit consuming gelatin
- Intolerance to small amounts of lactose (less than ½ teaspoonful) daily
- 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
Trial locations and contacts
18 sites in 1 country. Contact the study team or a site near you to ask about taking part.
18 sites in 1 country
United States18 sites
The University of Texas at Austin
Austin, Texas, 78712
Massachusetts General Hospital
Boston, Massachusetts, 02114
Atrium Health Wake Forest Baptist
Charlotte, North Carolina, 28203
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
Duke University Medical Center
Durham, North Carolina, 27710
Baylor College of Medicine
Houston, Texas, 77030
UTHealth Houston
Houston, Texas, 77030
Indiana University Health
Indianapolis, Indiana, 46202
University of Kentucky
Lexington, Kentucky, 40536
UW Health University Hospital
Madison, Wisconsin, 53792
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt University Medical Center
Nashville, Tennessee, 37203
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Virginia Commonwealth University
Richmond, Virginia, 23298
University of Utah
Salt Lake City, Utah, 84132
University of California, San Francisco
San Francisco, California, 94110
University of Washington
Seattle, Washington, 98104
About this study
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.
- Conditions
- Traumatic Brain Injury
- Being tested
- Atorvastatin Calcium, Minocycline Hydrochloride, Candesartan Cilexetil, Placebo
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atorvastatin CalciumDrug
Also called ATOR
Capsule, 80 mg/day, with no loading dose, for 28 days
Minocycline HydrochlorideDrug
Also called MINO
Capsule, 200 mg loading dose on Day 1, then 100 mg twice daily for 6 days, then placebo twice daily for 21 days
Candesartan CilexetilDrug
Also called CAND
Capsule, 8 mg once on Day 1, then 16 mg daily for 27 days
PlaceboDrug
Capsule, 2x/day for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Intervention 1: Atorvastatin calcium (ATOR) | Active comparator | By Mouth (PO) Twice a day (BID) 80 mg/day, with no loading dose, for 28 days Receives: Drug: Atorvastatin Calcium |
| Intervention 2: Minocycline hydrochloride (MINO) | Active comparator | 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 Receives: Drug: Minocycline Hydrochloride |
| Intervention 3: Candesartan cilexetil (CAND) | Active comparator | By Mouth (PO) Twice a day (BID) 8 mg once on Day 1, then 16 mg daily for 27 days Receives: Drug: Candesartan Cilexetil |
| Matching Placebo | Placebo comparator | By Mouth (PO) Twice a day (BID) 2 capsules 2x/day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glasgow Outcome Scale-Extended (GOSE 2-Way)
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.
Measured: 2 weeks to 3 months postinjury
Secondary outcomes (5)
Change in Blood-based biomarkers (Neurofilament light chain)
Neurofilament light chain (NfL) levels postinjury in participants with TBI will be measured and compared to placebo
Measured: Week 2
Blood-based biomarker (GFAP)
GFAP levels postinjury in participants with TBI as compared to placebo
Measured: Week 2
Imaging biomarkers
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.
Measured: 2 weeks to 3 months postinjury
Post-TBI cognitive outcome (BTACT)
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
Measured: Day 3 to Week 4 postinjury
Post-TBI symptom outcome (Rivermead)
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
Measured: Day 3 to Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2023
- Study start1 Aug 2024
- Primary completion31 Aug 2028 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 672 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Geoffrey Manley, MD PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05826912
- Sponsor's protocol ID
- APT-TBI-01
- Acronym
- APT-TBI-01
- Status last verified
- Dec 2025
- First submitted
- 12 Apr 2023
- Last updated
- 22 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be made available through the Federal Interagency TBI Research (FITBIR) Database.
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Arm Multi-Stage Adaptive Platform Trial (APT) for the Acute Treatment of Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT05826912
- Acronym / sponsor ID
- APT-TBI-01 / APT-TBI-01
- Conditions
- Traumatic Brain Injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 672 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 1 Aug 2024 (actual)
- Primary completion
- 31 Aug 2028 (estimated)
- Study completion
- 31 Aug 2029 (estimated)
- First posted
- 24 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Intervention 1: Atorvastatin calcium (ATOR) | Active comparator | Drug: Atorvastatin CalciumBy Mouth (PO) Twice a day (BID) 80 mg/day, with no loading dose, for 28 days |
| Intervention 2: Minocycline hydrochloride (MINO) | Active comparator | Drug: Minocycline HydrochlorideBy 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 |
| Intervention 3: Candesartan cilexetil (CAND) | Active comparator | Drug: Candesartan CilexetilBy Mouth (PO) Twice a day (BID) 8 mg once on Day 1, then 16 mg daily for 27 days |
| Matching Placebo | Placebo comparator | Drug: PlaceboBy Mouth (PO) Twice a day (BID) 2 capsules 2x/day |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adults (18-65 years of age, inclusive)
- 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.
- Closest, prior to Randomization Glasgow Coma Scale (GCS) score of 9 to 15
- Acute trauma-related neuroimaging abnormality (subarachnoid hemorrhage, contusion, subdural hematoma, petechial hemorrhage, intraventricular hemorrhage) on cranial CT (CT+)
- 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)
Key exclusion criteria (14 listed)
- Isolated epidural hematoma
- 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
- Current enrollment in another interventional study
- Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6 months
- Current incarceration or in custody
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atorvastatin CalciumAlso: ATORCapsule, 80 mg/day, with no loading dose, for 28 days | Drug | Intervention 1: Atorvastatin calcium (ATOR) |
| Minocycline HydrochlorideAlso: MINOCapsule, 200 mg loading dose on Day 1, then 100 mg twice daily for 6 days, then placebo twice daily for 21 days | Drug | Intervention 2: Minocycline hydrochloride (MINO) |
| Candesartan CilexetilAlso: CANDCapsule, 8 mg once on Day 1, then 16 mg daily for 27 days | Drug | Intervention 3: Candesartan cilexetil (CAND) |
| PlaceboCapsule, 2x/day for 28 days | Drug | Matching Placebo |
Primary outcome
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.
5 secondary outcomes
Change in Blood-based biomarkers (Neurofilament light chain)
Time frame: Week 2
Blood-based biomarker (GFAP)
Time frame: Week 2
Imaging biomarkers
Time frame: 2 weeks to 3 months postinjury
Post-TBI cognitive outcome (BTACT)
Time frame: Day 3 to Week 4 postinjury
Post-TBI symptom outcome (Rivermead)
Time frame: Day 3 to Week 4
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2025.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data will be made available through the Federal Interagency TBI Research (FITBIR) Database.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Geoffrey Manley, MD PhD principal investigator
University of California, San Francisco
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atorvastatin Calcium, Minocycline Hydrochloride and Candesartan Cilexetil in people with Traumatic Brain Injury, run by University of California, San Francisco at 18 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Glasgow Outcome Scale-Extended (GOSE 2-Way) (time frame: 2 weeks to 3 months postinjury). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2025.