Cyclosporine for Traumatic Brain Injury

(PM-003 Trial)

Overseen By Jasmin Hutyra

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Immunosuppressants, Contraindicated medications

Disqualifiers: Pregnancy, Renal dysfunction, Hepatic disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 week

26 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 drug listed below is approved by the U.S. Food and Drug Administration (FDA) but is being used "off-label" in this study. This means that the drug is not currently approved to treat TBI.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that ongoing pre-injury therapy with the investigational product or any contraindicated medications is an exclusion criterion. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Cyclosporine (CsA) for traumatic brain injury?

Research shows that Cyclosporine A (CsA) has potential neuroprotective effects in animal models of traumatic brain injury, reducing brain damage by about 50%. It works by protecting the brain's mitochondria (energy-producing parts of cells) from damage, which may help improve outcomes after injury. ^{1 2 3 4 5}

Is cyclosporine safe for use in humans, especially for traumatic brain injury?

Cyclosporine A (CsA) has been shown to be generally safe in humans, including those with traumatic brain injury, based on clinical studies and trials. It has been used safely for decades in other conditions like transplantation, and recent studies suggest it is also safe for brain injury, though more research is ongoing to confirm this. ^{1 2 3 6 7}

How does the drug Cyclosporine differ from other treatments for traumatic brain injury?

Cyclosporine is unique because it targets the secondary injury process in traumatic brain injury by preventing mitochondrial dysfunction, which can help protect brain cells from further damage. This mechanism is different from other treatments that may not specifically address the mitochondrial permeability transition pore, a key factor in cell damage after brain injury. ^{1 2 4 7 8}

Research Team

Geoffrey Manley, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for individuals who have suffered from subcortical brain damage or traumatic brain injury. Participants must meet certain health criteria to be included, but specific inclusion details are not provided here.

Inclusion Criteria

Initial GFAP blood level >1000 pg/mL ≤ 15000 pg/mL determined using a RUO or IUO assay

My recent GCS score was between 3 and 8.

I have had a brain injury confirmed by a CT scan.

Exclusion Criteria

I have a blood clot between my skull and brain.

My pupils are dilated and do not respond to light, not due to medications or brain herniation.

On psychiatric hold (e.g. Codes 5150, 5250)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Cyclosporine (CsA) or a matching placebo via intravenous injection over a period of 74 hours

1 week

1 visit (in-patient)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at Week 2, Week 4, Month 3, and Month 6

6 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Cyclosporine (CsA)

Trial Overview The study is testing the effectiveness of Cyclosporine (CsA), an FDA-approved drug used off-label, against a placebo in improving recovery after traumatic brain injury. Recovery progress will be monitored throughout the study.

Participant Groups

Group I: Cyclosporine (CsA) Active Control 1 Intervention

Intravenous (IV) injection, 2.5 mg/kg loading dose given over 2 hours, followed by a 3-day (72-hour) constant IV infusion of 5 mg/kg/day.

Group II: Matching Placebo Placebo Group 1 Intervention

Intravenous (IV) injection of 0.9% NaCl over 74 hours.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

U.S. Army Medical Research and Development Command

Collaborator

Trials

296

Recruited

249,000+

References

1. England pubmed.ncbi.nlm.nih.gov

Cyclosporine A for neuroprotection: establishing dosing guidelines for safe and effective use. [2013]

2. India pubmed.ncbi.nlm.nih.gov

The efficacy of Cyclosporine-A on Diffuse Axonal Injury after Traumatic Brain Injury. [2021]

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

A review of laboratory and clinical data supporting the safety and efficacy of cyclosporin A in traumatic brain injury. [2013]

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

Cyclosporin A significantly ameliorates cortical damage following experimental traumatic brain injury in rodents. [2013]

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

Cyclosporin A disposition following acute traumatic brain injury. [2013]

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

Dosing and safety of cyclosporine in patients with severe brain injury. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Modified calcium accumulation after controlled cortical impact under cyclosporin A treatment: a 45Ca autoradiographic study. [2013]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of chronic, post-injury Cyclosporin A administration on motor and sensorimotor function following severe, experimental traumatic brain injury. [2013]