Pro-2-Cool Pivotal Trial II

A Double-Blind, Randomized Study of Clinical Efficacy of Hypothermic Therapy Following Concussion in Adolescent Athletes as Compared to a Sham-Controlled Population

This study is being conducted to determine the clinical safety and efficacy of Pro-2-Cool mediated head and neck cooling when applied after concussion and improved symptomatology among adolescent athletes as quantified by post-concussion symptom severity (PCSS) score.

This is a multi-center, prospective, randomized, double-blinded, dual-arm comparative study enrolling up to a total of 66 patients (approximately 33 patients in the treatment arm and 33 patients in the control arm) following sports-related, concussion.

Inclusion Criteria:

1. Males and females, 13-21 years of age

2. Confirmed concussion diagnosis consistent with American Congress Rehabilitation Medicine guidelines 21, without any of the following:

   • Glasgow Coma Scale (GCS) score of less than 13 at 30 minutes post-injury
   • Loss of consciousness greater than 30 minutes
   • Post-traumatic amnesia lasting over 24 hours

3. Glasgow Coma Scale (GCS) ≥ 13 at the time of initial injury for study enrollment.

4. Post-Concussion Symptom Scale Score minimum of 15

5. Initial provider visit is within 7 days of injury

6. In generally good health as confirmed by medical history and determined by site investigator or designated trained healthcare professional under the supervision of the principal investigator.

7. Has informed consent obtained per protocol and as required per Institutional Review Board

Exclusion Criteria:

1. Age < 13 years or > 21 years

2. Inability to understand the study requirements or provide informed consent

3. Cleared to return to play during initial visit

4. Prior participation in a Pro2Cool Clinical Study

5. Serious traumatic brain injury as evidenced by worsening symptoms:

   • Vomiting > 2 episodes following injury
   • Seizure
   • Hospitalization
   • Radiology scan indicating brain bleed
   • Slurred speech which has not resolved within 72 hours of concussive injury

6. Physical (e.g., head or neck injury that requires medical treatment) or mental disability hindering adequate response to assessment of symptoms

7. Hemodynamic instability/medical condition requiring further acute life-saving medical intervention

8. History of psychiatric disorder that includes suicide attempts within the last 6 months, unmanaged depression or anxiety, hospitalization for psychiatric treatment within the last 6 months

9. Known brain mass, intracranial hemorrhage, skull fracture

10. Scalp abnormalities including laceration or bleeding

11. Presence of ventriculoperitoneal (VP) shunt

12. Known hematological malignancies, including, but not limited to: multiple myeloma, leukemia, and lymphoma

13. Known history of Reynaud's Disease compromised liver function, cold agglutination, cold sensitivity, cryoglobulinemia, cryofibrinogenemia, and/or a history of severe migraines

14. Known or disclosed pregnancy or breast-feeding

15. Sustains another head or neck injury at the time of concussive injury which requires medical treatment