Multi-Drug Therapy for Traumatic Brain Injury

(APT-TBI-01 Trial)

Recruiting at 1 trial location

Overseen By Jasmin Hutyra

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Investigational drugs

Disqualifiers: Pregnancy, Renal dysfunction, Liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

672 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Atorvastatin Calcium for treating traumatic brain injury?

Research shows that Atorvastatin can improve neurological function and promote brain healing in rats with traumatic brain injury. In humans, it was associated with better functional outcomes in patients with moderate to severe brain injury, even though it did not reduce brain contusion size. ^{1 2 3 4 5}

Is the multi-drug therapy for traumatic brain injury safe for humans?

Atorvastatin, one of the drugs in the therapy, was tested in a clinical trial for mild traumatic brain injury and was found to be safe for use in humans, with no serious adverse events reported. ^{1 2 3 4 6}

How is the multi-drug therapy for traumatic brain injury unique?

This multi-drug therapy is unique because it combines atorvastatin, candesartan, and minocycline, which have shown potential benefits in experimental models of traumatic brain injury (TBI) by reducing neurological deficits, promoting brain cell survival, and enhancing recovery, unlike single-drug treatments that have failed in clinical trials. ^{1 2 3 4 7}

Research Team

Geoffrey Manley, MD PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

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.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Intervention 1: Atorvastatin calcium (ATOR) Active Control 1 Intervention

By Mouth (PO) Twice a day (BID) 80 mg/day, with no loading dose, for 28 days

Group II: Intervention 2: Minocycline hydrochloride (MINO) Active Control 1 Intervention

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

Group III: Intervention 3: Candesartan cilexetil (CAND) Active Control 1 Intervention

By Mouth (PO) Twice a day (BID) 8 mg once on Day 1, then 16 mg daily for 27 days

Group IV: Matching Placebo Placebo Group 1 Intervention

By Mouth (PO) Twice a day (BID) 2 capsules 2x/day

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

Approved in European Union as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in United States as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease
• Reduction of risk of myocardial infarction, stroke, angina, and revascularization procedures

Approved in Canada as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in Japan as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in China as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in Switzerland as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II Clinical Trial of Atorvastatin in Mild Traumatic Brain Injury. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Minocycline synergizes with N-acetylcysteine and improves cognition and memory following traumatic brain injury in rats. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Atorvastatin reduction of intracranial hematoma volume in rats subjected to controlled cortical impact. [2018]

5. Scotland pubmed.ncbi.nlm.nih.gov

Effects of atorvastatin on brain contusion volume and functional outcome of patients with moderate and severe traumatic brain injury; a randomized double-blind placebo-controlled clinical trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

The Neuroprotective Effects of Simvastatin on High Cholesterol Following Traumatic Brain Injury in Rats. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Statins improve outcome in murine models of intracranial hemorrhage and traumatic brain injury: a translational approach. [2021]