Multi-Drug Therapy for Traumatic Brain Injury

(APT-TBI-01 Trial)

Enrolling by invitation at 14 trial locations
GS
JH
Overseen ByJasmin Hutyra
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: University of California, San Francisco
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if specific drugs can improve recovery after a traumatic brain injury (TBI). It tests three medications—atorvastatin (a cholesterol-lowering drug), candesartan (a blood pressure medication), and minocycline (an antibiotic)—already approved for other uses, to see if they can speed up or enhance healing when used together. Individuals with a non-penetrating head injury, showing signs like a brain bleed or swelling on a CT scan, may be suitable candidates. Participants will receive either one of these drugs or a placebo (a pill with no active drug) to compare outcomes. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking one of the investigational drugs or similar ones. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that atorvastatin improves recovery in people with traumatic brain injury (TBI) without increasing the risk of brain swelling. It also reduces inflammation in the brain after an injury. Researchers have tested minocycline and found it safe even at higher doses than those used for treating infections, indicating it is likely well-tolerated. Candesartan has been deemed safe in other conditions and may improve blood flow in the brain after TBI. The FDA has approved all three drugs for other uses, suggesting they are generally safe when taken as directed.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for traumatic brain injury because they offer unique approaches compared to traditional options like surgery or rehabilitation therapies. Atorvastatin calcium is known for its cholesterol-lowering effects, but here it’s being explored for its potential to reduce inflammation in the brain. Minocycline hydrochloride, typically an antibiotic, might have neuroprotective properties that help shield brain tissue from further damage. Candesartan cilexetil, usually used for blood pressure control, could offer benefits by improving blood flow to the brain. These diverse mechanisms might provide new ways to manage and improve outcomes for patients with traumatic brain injury.

What evidence suggests that this trial's treatments could be effective for traumatic brain injury?

This trial will evaluate multiple treatments for traumatic brain injury (TBI). Research has shown that atorvastatin calcium, one treatment in this trial, might help reduce inflammation in people with TBI. However, other studies did not find it significantly improved overall recovery. Minocycline hydrochloride, another treatment option, has shown promise in animal studies by helping the brain heal and reducing damage after TBI. Some research suggests it can shrink brain lesions and improve brain function. Candesartan cilexetil, also tested in this trial, might help by boosting blood flow in the brain and protecting the brain's barrier, which can be beneficial after TBI. While these drugs have shown potential in some studies, more research is needed to confirm their effectiveness for TBI recovery in humans.678910

Who Is on the Research Team?

GM

Geoffrey Manley, MD PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with a recent non-penetrating head injury and specific CT scan findings. Participants must have certain protein levels in their blood, be able to undergo MRI scans without sedation, use birth control if applicable, and not have severe allergies or organ dysfunction. They should also not be on the study drugs already or enrolled in another interventional study.

Inclusion Criteria

My GFAP blood level is between 100 and 15,000 pg/ml.
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
Participants able to undergo magnetic resonance imaging (MRI) scans, no contraindications or need for sedation
See 7 more

Exclusion Criteria

Hypersensitivity or intolerance to investigational products or the investigational products respective classes
Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6 months
I am currently taking or cannot take the trial drug due to health reasons.
See 10 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive experimental drug treatment to improve recovery after TBI. Atorvastatin calcium, Minocycline hydrochloride, and Candesartan cilexetil are administered for 28 days.

4 weeks
Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with changes in recovery measured using various biomarkers and cognitive assessments.

3 months

What Are the Treatments Tested in This Trial?

Interventions

  • Atorvastatin Calcium
  • Candesartan Cilexetil
  • Minocycline Hydrochloride
  • Placebo
Trial Overview The trial tests Atorvastatin Calcium, Minocycline Hydrochloride, Candesartan Cilexetil against a placebo to see if they improve recovery from traumatic brain injury (TBI). These FDA-approved drugs are used 'off-label' here since they're not specifically approved for TBI treatment.
How Is the Trial Designed?
4Treatment groups
Active Control
Placebo Group
Group I: Intervention 1: Atorvastatin calcium (ATOR)Active Control1 Intervention
Group II: Intervention 2: Minocycline hydrochloride (MINO)Active Control1 Intervention
Group III: Intervention 3: Candesartan cilexetil (CAND)Active Control1 Intervention
Group IV: Matching PlaceboPlacebo Group1 Intervention

Atorvastatin Calcium is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

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Approved in European Union as Lipitor for:
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Approved in United States as Lipitor for:
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Approved in Canada as Lipitor for:
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Approved in Japan as Lipitor for:
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Approved in China as Lipitor for:
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Approved in Switzerland as Lipitor for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials
2,636
Recruited
19,080,000+

United States Department of Defense

Collaborator

Trials
940
Recruited
339,000+

Citations

The neuroprotective effect of statin in traumatic brain injuryStatin improves neurofunctional outcomes after traumatic brain injury. Statin provides immunomodulating effects after traumatic brain injury.
Effect of statins on neurological functional outcomes in ...We found no conclusive evidence supporting the use of statins in critically ill adult patients with TBI at this time.
Effects of Statin Treatment on Outcomes after Traumatic ...Evidence of greater and lesser statin compliance was not associated with outcome. This study did not provide support for a clinically important benefit of ...
Statins' Effect on Cognitive Outcome After Traumatic Brain InjuryThis study concluded that atorvastatin has no beneficial effect on the expansion rate of cerebral contusions in patients with moderate and ...
The Effect of Low-Dose Atorvastatin on Inflammatory ...This study demonstrated that Atorvastatin could reduce the rate of inflammatory factors in TBI patients. The inflammatory condition of TBI patients heavily ...
The neuroprotective effect of statin in traumatic brain injuryStatin improves neurofunctional outcomes after traumatic brain injury. •. Statin provides immunomodulating effects after traumatic brain injury. •. Statin ...
Review article Statins in Traumatic Brain InjuryPreclinical studies have shown significant benefit of statins in models of TBI and related disease processes, including cerebral ischemia, intracerebral ...
Effects of atorvastatin on brain contusion volume and ...Atorvastatin improved functional outcomes at 3-months following moderate to severe TBI. •. Atorvastatin was not associated with reduction in the rate of brain ...
Anti-inflammatory and immunomodulatory mechanisms of ...Our data demonstrated that acute atorvastatin administration could modulate post-TBI neuroinflammation effectively.
Evaluation of the Effect of Atorvastatin Administration on ...Conclusions: The results revealed the positive effect of atorvastatin on the improvement of outcomes measurements such as GCS,. DRS, and GOS in ...
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