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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether an experimental drug, Cyclosporine (an immunosuppressant), can improve recovery after a traumatic brain injury (TBI). Researchers will compare the results of participants receiving the drug to those receiving a placebo (a non-active treatment). It is important to note that while the FDA has approved Cyclosporine for other uses, it is not yet approved specifically for TBI. This trial may suit someone who recently sustained a head injury serious enough to require a CT scan and can begin treatment quickly thereafter. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Cyclosporine is likely to be safe for humans?

Research has shown that cyclosporine (CsA) is generally safe and well-tolerated for traumatic brain injury (TBI). In studies where CsA was administered soon after a severe TBI, patients tolerated it well. Another study found that continuous use of CsA for five days was safe for patients with severe TBI. While these studies suggest CsA is generally safe, it is being used in a new way for this trial. Participants should discuss any concerns about joining with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for TBI?

Researchers are excited about using cyclosporine for traumatic brain injury (TBI) because it tackles the condition in a novel way. Unlike most TBI treatments that mainly focus on alleviating symptoms or reducing swelling, cyclosporine works by protecting brain cells from further damage. It does this by inhibiting the opening of the mitochondrial permeability transition pore, which can help prevent cell death after a brain injury. This unique mechanism of action offers hope for better outcomes in TBI patients, potentially preserving brain function more effectively.

What evidence suggests that Cyclosporine might be an effective treatment for TBI?

Research has shown that cyclosporine (CsA) may help treat traumatic brain injury (TBI). Studies have found that CsA can protect brain cells from damage. In animal studies, CsA reduced brain damage by about 50%. Other research showed that CsA improves recovery when given in the right amount. In this trial, participants will receive either CsA or a matching placebo to evaluate its effectiveness specifically for TBI recovery. The FDA has already approved this treatment for other uses, but it is being tested here specifically for TBI. ^{6 7 8 9 10}

Who Is on the Research Team?

Geoffrey Manley, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10684836/

Cyclosporine as Therapy for Traumatic Brain Injury - PMC Overall, most in vivo studies have demonstrated beneficial effects of cyclosporine on the evaluated outcome measures. A few studies have found ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21307793/

A review of laboratory and clinical data supporting the ... In the past 10 years, this agent has shown neuroprotective effects in animal models of traumatic brain injury (TBI).

3. mdpi.com mdpi.com/1422-0067/26/8/3531

Cyclosporine A Accelerates Neurorecovery Transcriptional ... Previously, we demonstrated the pleiotropic effects of CsA in improving TBI outcomes in a dose-dependent manner in 4-week-old piglets who received a sagittal ...

4. withpower.com withpower.com/trial/cyclosporine-for-traumatic-brain-injury-3d1a0

Cyclosporine for Traumatic Brain Injury (PM-003 Trial) Research shows that Cyclosporine A (CsA) has potential neuroprotective effects in animal models of traumatic brain injury, reducing brain damage by about 50%.

5. journals.lww.com journals.lww.com/adbm/fulltext/2014/03000/the_efficacy_of_cyclosporine_a_on_diffuse_axonal.35.aspx

The efficacy of Cyclosporine-A on Diffuse Axonal Injury... Our results suggest that CsA administration to patients with DAI during first 8 h after damage with the dose of 5 mg/kg for 24 h is safe and no clinically ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2824218/

Safety and Tolerability of Cyclosporin A in Severe ... This study demonstrates the good safety and tolerability profile of CsA when it is administered early after severe TBI with the goal of neuroprotection.

7. sciencedirect.com sciencedirect.com/science/article/pii/S187874792301992X

Cyclosporine as Therapy for Traumatic Brain Injury A systematic review and meta-analysis concluded that TBI patients with DAI have a three times higher risk of an unfavorable outcome than TBI patients without ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2770729/

Dosing and safety of cyclosporine in patients with severe brain ... Postinjury administration of cyclosporine resulted in a 40% reduction in lesion volume.

9. liebertpub.com liebertpub.com/doi/10.1089/neu.2018.6369

Copenhagen Head Injury Ciclosporin Study: A Phase IIa ... This study indicates that ciclosporin administered continuously for 5 days, using a novel lipid emulsion formulation, is safe and well tolerated in severe TBI ...

10. scholars.uky.edu scholars.uky.edu/en/publications/dosing-and-safety-of-cyclosporine-in-patients-with-severe-brain-i/

Dosing and safety of cyclosporine in patients with severe brain ... Object. Cyclosporine neuroprotection has been reported in brain injury models but safety and dosing guidelines have not been determined in humans with ...