The Efficacy of Familiar Voice Stimulation During Coma Recovery

Study Overview
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Brief Summary
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The purpose of the study is to determine whether familiar vocal stimulation, provided during coma recovery, improves outcomes for persons who are unconscious after severe TBI. The primary hypothesis is that unconscious persons who receive standard rehabilitation (SR) plus a high-dose of Familiar Voice stimulation (FVs) compared to unconscious persons who receive SR plus a sham stimulation (Sham Group) will demonstrate: Significantly more neurobehavioral functioning post-intervention compared to pre-intervention. Using Functional Magnetic Resonance Imaging (fMRI), significantly higher average measures of volumetric activity in the whole brain, middle temporal gyrus bilaterally, primary auditory area, bilateral pre-frontal cortex, hippocampus and/or the cerebellum post-intervention compared to pre-intervention.

Detailed Description
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Medical advances have improved the odds of surviving a severe traumatic brain injury (TBI) thereby increasing demands for rehabilitation. Medical rehabilitation management during coma recovery, however, has been hampered by a paucity of rigorous clinical trials examining rehabilitation effectiveness. This randomized clinical trial addresses this knowledge gap. The purpose of the study is to determine whether a high dose of familiar vocal stimulation (FVs) improves outcomes for persons who are unconscious after severe TBI. The research objectives are to: Determine whether neural responses elicited with FVs improve neurobehavioral outcomes and/or elicit activations in expected regions. Examine the relationship between neurobehavioral and neurophysiological responses to high doses of FVs during coma recovery. There are two study cohorts and each group receives standard rehabilitation. The experimental group will be exposed daily to 40 minutes of FVs for 6 weeks. The Sham Group (Control Group 2) will receive 40 minutes of sham treatment, or silence, daily for 6 weeks. The 40 minutes of FVs treatment will be provided in four 10 minute sessions. Each FV session will start with the subject hearing a familiar voice call the 'Subject's Own Name' aloud and then that same voice re-telling a memory or an event familiar to the subject. The person re-telling the event will be a person who experienced the event with the subject and who interacted with the subject on a daily basis for at least 1 year prior to injury.

Official Title
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Can Neural Adaptation After Severe Brain Injury be Facilitated?

Conditions
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Traumatic Brain Injury, Coma, Vegetative State, Minimally Conscious State

Intervention / Treatment
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* Behavioral: Familiar Auditory Sensory Training
* Behavioral: Sham Auditory Sensory Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe brain injury of traumatic origin Non-brain penetrating gun shot wound Blunt trauma with subsequent closed head injuries such as diffuse axonal injury 18 years of age or older Unconscious for at least 28 days consecutively Medically Stable Does not have active seizures Exclusion Criteria: History of brain injury More than 1 year post injury MRI is contraindicated (e.g., metal, titanium in brain) Ventilator dependent Cardiac contraindications The definition of traumatic brain injury excludes: (a) Lacerations or contusions of the face, eye, ear or scalp and fractures of facial bones with-out loss of consciousness; (b) Primary cause of injury is blunt trauma (e.g., contusion from blow to head) without subsequent closed head injuries such as contra coup or diffuse axonal injury; (c) Brain-penetrating gun shot wound; (d) Primary BI due to anoxic, inflammatory, infectious, toxic metabolic encephalopathies; (e) Cancer, brain infarction (ischemic stroke), intracranial hemorrhage (hemorrhagic stroke) aneurysms and arterio-venous malformations.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: Familiar Auditory Sensory Training<br>FAST is a standardized passive auditory stimulation protocol. The patient is provided with customized recordings of stories told by people well known to the patient at least 1 year prior to injury. The stories represent specific events experienced by both the patient and the storyteller. The FAST protocol is provided on compact discs (CDs), using portable players and noise cancelling headphones, while patients were awake (ie, eyes open). Speakers were used for one patient not tolerating his headphones. The CDs were identical according to track duration, labeling, and administration procedures. | Behavioral: Familiar Auditory Sensory Training<br>* Patient is provided with customized recordings of stories told by people well known to the patient at least 1 year prior to injury. The stories represent specific events experienced by both the patient and the storyteller. Patients received FAST for 10 minutes 4 times per day, with at least 2 hours in between, for 6 week.<br>|
| Sham Comparator: Sham Auditory Sensory Training<br>Placebo protocol is silence. Patients receive sham protocols for 10 minutes 4 times per day, with at least 2 hours in between, for 6 weeks. | Behavioral: Sham Auditory Sensory Training<br>* The sham intervention is zero minutes of Familiar Auditory Sensory Training. Each day for 6 weeks 0 minutes of Familiar voice stimulation will be provided in 10 minute daily segments for 6 weeks. Each 10 minute recording is a digital recording of silence.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DOCS Neurobehavioral Measure (DOCS = Disorders of Consciousness Scale) Change | The primary outcome, the DOCS, is a reliable, valid and precise measure of global neurobehavioral functioning shown to remain stable over six weeks.The DOCS-25 starts with a systematic observation followed by administration of 25 sensory stimuli. Best responses to each stimulus are rated on a scale of 0 to 2 and total raw scores range from 0 (worst) to 50 (best). The DOCS change was calculated as the value at endpoint (6 weeks after Baseline) minus the value at Baseline. | Baseline and immediately after treatment ends (6 weeks after Baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coma Near Coma Scale | The CNC scale measures arousal and awareness and test stimuli are administered to elicit a specified behavior. Presence/absence of this behavior is scored as 0, 2 or 4. Total raw scores range from 0 (consistently responsive) to 36 (extreme coma). The CNC change score was calculated as the 8th CNC measure minus the Baseline CNC measure. Since 2 CNC measurements were collected per week, the 8th CNC measure occurred in Week 4. To calculate the change, we used the eighth CNC measure because two patients (one per group) recovered full consciousness after the eighth CNC measure. In the second statistical analysis, all CNC measures were used to calculate the slope; this includes the Baseline CNC and CNC measures 2-8. Again, we used the first 8 CNC measures (instead of all 12 collected over 6 weeks of treatment) because two patients recovered full consciousness after the eighth CNC measure. | Baseline and after the 8th CNC assessment (4 weeks after Baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized Clinical Trial, Auditory Stimulation