A Study of IBRF Disorders of Consciousness Advanced Care/MultiModal Care Protocol in Severe Disorders of Consciousness

Study Overview
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Brief Summary
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This is a study to evaluate the safety and efficacy of the IBRF ACP/MCP intervention protocol in patients with severe disorders of consciousness (SDOC).

Detailed Description
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Currently, there are no empirically validated, evidence-based pharmacological interventions for the treatment of Severe Disorders of Consciousness (SDOC). In addition, it is unclear why poly-pharmacological interventions, while more common in the treatment of other disorders (e.g., cancer, chronic pain), have not been embraced for the treatment SDOC; some of the lone agents used in treatment of SDOC patients are not indicated for combined treatment. In addition, the treatment of SDOC traditionally employs the use of single or small combinations of pharmacological agents, with no single pharmacological agent being identified as efficacious or effective. As such, a poly-pharmacological intervention may, inherently, involve pharmacological interactions that were not anticipated by the drug manufacturers or prescribing physicians. The purpose of this study is to document the safety of the IBRF ACP/MCP and to establish its efficacy for those SDOC patients successfully completing treatment. The IBRF ACP/MCP employs a poly-pharmacological approach aimed at studying arousal states and outcomes in SDOC patients beyond those rates documented in literature.

Official Title
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A Phase 1/2,Open-Label Study to Evaluate the Safety and Efficacy of the International Brain Research Foundation (IBRF) Disorders of Consciousness Advanced Care/MultiModal Care Protocol in Patients With Severe Disorders of Consciousness

Conditions
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Brain Injury

Intervention / Treatment
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* Drug: Polypharmacy using FDA-approved products
* Device: Median Nerve Stimulation (MNS)
* Dietary Supplement: Nutraceutical Supplementation
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years to ≤ 65 years GCS rating of 3 to 9 (severe impairment) Evidence of an acquired brain injury that severely suppresses consciousness Coma, vegetative state, or minimally conscious state based on definitions of the Mohonk Report If polytrauma, patient is medically stable Exclusion Criteria: GCS of 10 or greater (moderate to mild impairment) Tracheostomies requiring ventilator support Medical condition that precludes objective assessment (e.g., concurrent Guillain-Barre or other severe peripheral neuropathy, severe critical illness myopathy/polyneuropathy) Onset of injury greater than 12 months post hypoxic ischemic injury (HII) Onset of injury greater than 24 months post traumatic brain injury (TBI) Emergence during the screening period Terminal illnesses, existing severe neuro-developmental disorders, existing chronic degenerative neurological conditions, prior moderate-to-severe TBI, or any stroke syndrome other than transient ischemic attack (TIA), or a prior seizure disorder Patients with an uncontrolled seizure disorder, or seizure disorder can only be controlled with medication that is contra-indicated (e.g., dilantin or phenobarbitol), In the opinion of the attending physician, the patient presents with a cardiac condition that would place them at unacceptable risk, or has a documented ejection fraction (EF) <25%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBRF ACP/MCP Group 1<br>The Treatment group will be receiving a combination of pharmaceuticals (polypharmacy using FDA-approved products) and nutraceuticals (Nutraceutical supplementation) and median nerve stimulation (MNS) | Drug: Polypharmacy using FDA-approved products<br>* Battery of medications provided through a 12-week schedule including: Minocycline, Lamotrigine, Flumazenil, Modafinil, Bromocriptine, Donepezil, Methylphenidate, Methyl B12, Methylfolate, Rasagiline, Amantadine, Naltrexone and Levodopa/carbidopa.<br>* Other names: Minocycline, Lamotrigine, Flumazenil, and others;Device: Median Nerve Stimulation (MNS)<br>* 40 cycle/second (gamma range) asymmetric, 2 ms wavebands with 300 µs bursts at 20 milliamps bilaterally (randomized left arm and right arm sequencing algorithm) applied 20 seconds on and 40 seconds off for 8 hours per day.<br>* Other names: Empi PV300 TENS;Dietary Supplement: Nutraceutical Supplementation<br>* Battery of nutraceuticals provided through a 12-week schedule including: Acidophilus, Alpha-Lipoic Acid, Acetyl L-Carnitine,<br>* Other names: Acidophilus, Alpha-Lipoic Acid, and others;Other: Standard of Care<br>* Standard of Care treatment<br>|
| Other: Standard of Care Group 2<br>Standard of Care only | Other: Standard of Care<br>* Standard of Care treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance to treatment | The percent of patients completing the treatment protocol | Week 12 | 
| Number and Frequency of side effects | The total number and frequency of side effects experienced by patients based on observations and evaluations of the patients' clinical laboratory tests | Week 12 | 
| Adverse events | Based on observations of the study patients and evaluations of clinical laboratory tests | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| coma recovery scale-revised (CRS-R) |  | Week 12 | 
| disability rating scale (DRS) |  | Week 12 | 
| functional assessment measure (FIM) |  | Week 12 | 
| Glasgow coma scal (GCS) |  | Week 12 | 
| Glasgow outcome scale-extended (GOS-E) |  | Week 12 | 
| orientation log (O-LOG) |  | Week 12 | 
| vegetative state (VS) | Clinical diagnosis (, minimally conscious state; MCS, emerged) using criteria from the Mohonk Reports | Week 12 | 
| minimally conscious state (MCS) |  | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe Disorders of Consciousness (SDOC), Coma, Vegetative State, Minimally Conscious State