Ghrelin (OXE--103) for Acute Concussion Management

Study Overview
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Brief Summary
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Concussions are the leading form of mild traumatic brain injury. Management of concussions and mild traumatic brain injury is a high priority medical focus, social concern, and research topic. Currently, there are no FDA approved treatments for acute concussion. The current standard of care is rest followed by gradual return to normal activity. The purpose of this study is to show improvement in the way patients feel or function after a concussion. OXE-103 is a protein hormone produced in the laboratory which identical to the hormone ghrelin that is secreted by the stomach. This study will investigate the use of this hormone as treatment for symptoms of acute concussion. The goal of this study is to show improvement in the way study participants feel or function after concussion. An OXE-103 (ghrelin) agonist is already FDA approved for another condition, but not for concussion. For concussion, it is considered investigational. This study will examine, if ghrelin is taken every day for two weeks, if the brain will heal faster and help improve or resolve symptoms. The study will also include a placebo arm and a non-treatment group (for those who wish to participate but do not want to receive any treatment). The OXE-103 and placebo will be self-administered through injections using needles.

Detailed Description
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All consenting participants will be screened for eligibility. The study has two Parts: Part A: Post-Acute (within 28 days of injury) Part B: Acute (within 24 hours of injury) Part A does not include randomization and all enrolling subjects will be offered treatment with OXE-103. Enrolling subjects in this Part A will also have the option to choose participation in a non-treatment control group if they do not want treatment. Part B participation includes double-blinded randomization to receive either OXE-103 or placebo. There is no option to choose participation in a non-treatment control group. For Part B, consenting and eligible participants will either be randomized to receive study drug (OXE-103) or placebo. The study team will also be blinded to the assigned treatment, so they will not know which treatment participants have been assigned to take. Consenting participants must be willing to commit to the following: give themselves subcutaneous injections twice a day (for the treatment groups) attend several study visits, which require both in-person and phone-only visits complete various questionnaires and testing have blood drawn have ECG's performed undergo a pregnancy test (if of childbearing potential) and use contraception while on study (for the treatment groups) tell the study team about any side effects they might experience from the study drug during study participation Total participation for the treatment groups will last about 7 weeks, which includes screening, 14 days of taking the study drug, and 4 weeks of follow-up. Participation for the non-treatment group will last the same amount of time.

Official Title
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Ghrelin (OXE--103) for Acute Concussion Management

Conditions
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Concussion, Brain, Traumatic Brain Injury

Intervention / Treatment
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* Drug: Ghrelin (OXE-103)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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INCLUSION AND EXCLUSION: In Part A (post-acute), subjects must be consented within 28 days post injury. In Part B (acute), subjects must be consented, randomized, and start treatment within 24 hours of presentation to the University of Kansas Health System Trauma Unit. Subjects in both Part A and B will have a symptom severity score of at least 20 at the time of randomization in order to reduce the expected degree (number and severity) of spontaneous symptom resolution prior to study completion. Subjects with pre-existing neurologic conditions other than mTBI (including cognitive dysfunction) will be excluded. Subjects with concurrent long bone fractures or orbital fractures will be excluded. Subjects receiving, or planning to receive, a continuous ketamine infusion while enrolled in study will be excluded. Subjects with these known endocrinological abnormalities at baseline will be excluded from study: diabetes mellitus, excess or deficiency of growth hormone, cortisol, or prolactin. Exclusion from study for any other endocrinological abnormalities or diagnoses existing at baseline are ultimately up to the discretion of the study physician. Significant abnormalities in serum creatinine (>2.5 mg/dL), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of normal, or bilirubin (>2.5 mg/dL) will exclude subjects from participation. Subjects with any abnormal findings noted on imaging, such as hemorrhage, will be excluded from the study. Subjects who meet criteria for moderate or severe TBI will also be excluded. Subjects who are known to be pregnant will be excluded. Subjects who do not agree to double-barrier contraception or abstinence (for female subjects of child-bearing potential or male subjects who are sexually active with a female of child-bearing potential) until the day following last dose (total of at least 5 half-lives) will be excluded. In Part A subjects receiving other concomitant medications, physical therapy, or other treatments related to their current mTBI will be eligible if they meet the inclusion criteria. Subjects (or household members) who are not able to inject themselves or the subject will be excluded. For both Part A and Part B, subjects are not allowed to be concurrently enrolled in another therapeutic intervention clinical trial while participating in this study. Any subjects currently enrolled in such a separate therapeutic intervention clinical trial, for any condition, will be excluded from participating in this study. For clarification, this does not include observational clinical trials or registries. Ultimately study subject participation will be at the discretion of the study physician.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo (40ug/kg) will be self-administered twice daily for 14 days. ONLY THE PART B (ACUTE) SUBJECTS WILL BE RANDOMIZED AND MAY RECEIVE PLACEBO. | Drug: Placebo<br>* 40ug/kg twice daily by self-injection<br>|
| Experimental: Ghrelin (OXE-103)<br>OXE-103 (40ug/kg) will be self-administered twice daily for 14 days. PART A (POST-ACUTE) SUBJECTS WILL BE OFFERED EXPERIMENTAL TREATMENT WITHOUT RANDOMIZATION. PART B (ACUTE) SUBJECTS WILL BE DOUBLE-BLIND RANDOMIZED TO EXPERIMENTAL OR PLACEBO TREATMENT. | Drug: Ghrelin (OXE-103)<br>* 40ug/kg twice daily by self-injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom Management - Post Concussion Symptom Scale | The primary goal is to describe the change in number of symptoms and/or severity of symptoms in sub-acute concussion with treatment with OXE-103 using the Post Concussion Symptom Scale questionnaire during the intervention period at days 1 and 15 as well as during the post-treatment period at days 21 and 44. The Post Concussion Symptom Scale questionnaire consists of 23 common concussion symptoms which are assigned a ranking of severity on a scale from 0 (no symptom) to 6 (severe symptom). This tool is used to capture both severity of concussion symptoms as well as the number of symptoms. | Days 1-44 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life - QOLIBRI-OS | A secondary goal is to examine change in quality of life with treatment of sub-acute concussion using the Quality of Life after Brain Injury - Overall Scale questionnaire. The Quality of Life after Brain Injury - Overall Scale questionnaire consists of six questions which address satisfaction of life after injury. Responses are assigned a ranking on a scale from not at all to very. | Days 1-44 | 
| Quality of Life - PGAS | A secondary goal is to examine change in quality of life with treatment of sub-acute concussion using a Patient Global Assessment Scale, which is measured using a visual analogue scale. The range is from 0 (no impact) to 10 (greatest impact). This tool asks how concussion symptoms impact ability to function or perform daily activities. | Days 1-44 |