Trial Outcomes & Findings for Vestibular Consequences of Blast-related Mild Traumatic Brain Injury (TBI) (NCT NCT01021137)

NCT ID: NCT01021137

Last Updated: 2019-08-05

Results Overview

The caloric weakness was determined using monothermal warm inter-ear difference (MWIED) which was calculated as: (\|RW\| - \|LW\| )/( \|RW\| + \|LW\|) x 100, where RW = the maximum slow phase velocity (SPV) of nystagmus induced by warm water irrigation in the right ear and LW = the maximum SPV of nystagmus induced by warm water irrigation in the left ear. For participants with MWIED \> 10, then cool caloric irrigation was also performed and caloric weakness was determined using a bithermal inter-ear difference (BIED) calculated as: (\|RW\| + \|RC\|) - (\|LW\| + \|LC\|) / (\|RW\| + \|RC\| + \|LW\| + \|LC\|) x 100, where RC = maximum SPV of nystagmus induced by cool water irrigation in the right ear and LC = maximum SPV of nystagmus induced by cool water irrigation in the left ear.

• Recruitment status: COMPLETED
• Target enrollment: 140 participants
• Primary outcome timeframe: up to 30 minutes
• Results posted on: 2019-08-05

Participant Flow

140 Veterans were recruited for this study. Participants included Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans and healthy, age & gender matched controls. Veteran participants had a history of traumatic brain injury (TBI), blast exposure, or both.

Six participants were consented to participate in the study, but did not return to complete the protocol. Case history was not collected and therefore, the participants could not be assigned to any of the study groups.

Participant milestones

Measure	TBI & Blast OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI	Blast Only OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI	TBI Only OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure	Healthy Controls Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure
Overall Study STARTED	62	20	11	41
Overall Study COMPLETED	52	16	9	32
Overall Study NOT COMPLETED	10	4	2	9

Reasons for withdrawal

Measure	TBI & Blast OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI	Blast Only OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI	TBI Only OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure	Healthy Controls Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure
Overall Study Lost to Follow-up	9	4	2	6
Overall Study Withdrawal by Subject	1	0	0	3

Baseline Characteristics

Vestibular Consequences of Blast-related Mild Traumatic Brain Injury (TBI)

Baseline characteristics by cohort

Measure	TBI & Blast n=52 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI	Blast Only n=16 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI	TBI Only n=9 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure	Healthy Controls n=32 Participants Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure	Total n=109 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	51 Participants n=5 Participants	16 Participants n=7 Participants	9 Participants n=5 Participants	32 Participants n=4 Participants	108 Participants n=21 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Age, Continuous	37.1 years STANDARD_DEVIATION 9.9 • n=5 Participants	40.5 years STANDARD_DEVIATION 10.5 • n=7 Participants	39.7 years STANDARD_DEVIATION 10.9 • n=5 Participants	31.2 years STANDARD_DEVIATION 9.8 • n=4 Participants	35.9 years STANDARD_DEVIATION 10.6 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	7 Participants n=21 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	15 Participants n=7 Participants	8 Participants n=5 Participants	28 Participants n=4 Participants	102 Participants n=21 Participants
Region of Enrollment United States	52 Participants n=5 Participants	16 Participants n=7 Participants	9 Participants n=5 Participants	32 Participants n=4 Participants	109 Participants n=21 Participants

PRIMARY outcome

Timeframe: up to 30 minutes

Population: Caloric weakness could not be obtained from 1 participant in the Blast Only group and 2 participants in the Healthy Control group.

The caloric weakness was determined using monothermal warm inter-ear difference (MWIED) which was calculated as: (|RW| - |LW| )/( |RW| + |LW|) x 100, where RW = the maximum slow phase velocity (SPV) of nystagmus induced by warm water irrigation in the right ear and LW = the maximum SPV of nystagmus induced by warm water irrigation in the left ear. For participants with MWIED > 10, then cool caloric irrigation was also performed and caloric weakness was determined using a bithermal inter-ear difference (BIED) calculated as: (|RW| + |RC|) - (|LW| + |LC|) / (|RW| + |RC| + |LW| + |LC|) x 100, where RC = maximum SPV of nystagmus induced by cool water irrigation in the right ear and LC = maximum SPV of nystagmus induced by cool water irrigation in the left ear.

Outcome measures

Measure	TBI & Blast n=52 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI	Blast Only n=15 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI	TBI Only n=9 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure	Healthy Controls n=30 Participants Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure
Peripheral Vestibular Function (Vestibulo-ocular Reflex/Semicircular Canal): Caloric Weakness	8.8 percentage of caloric weakness Standard Deviation 8.5	14.7 percentage of caloric weakness Standard Deviation 20.8	12.3 percentage of caloric weakness Standard Deviation 5.6	7.1 percentage of caloric weakness Standard Deviation 6.0

PRIMARY outcome

Timeframe: up to 30 minutes

Population: Rotary chair slow harmonic acceleration (SHA) VOR gain at 0.01 Hz was not evaluated in 1 participant in the TBI \& Blast group.

Rotary chair slow harmonic acceleration (SHA) vestibulo-ocular reflex (VOR) gain at 0.01 Hz was used as a measure of peripheral vestibular function (VOR/horizontal semicircular canal). VOR gain is defined as the ratio of the slow component velocity eye movement (output) to the velocity of the head movement (input).

Outcome measures

Measure	TBI & Blast n=51 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI	Blast Only n=16 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI	TBI Only n=9 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure	Healthy Controls n=32 Participants Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure
Rotary Chair Slow Harmonic Acceleration (SHA) Gain	.4 Unitless Standard Deviation .1	.4 Unitless Standard Deviation .1	.4 Unitless Standard Deviation .1	.4 Unitless Standard Deviation .1

PRIMARY outcome

Timeframe: Up to 30 minutes

Population: Cervical VEMP could not be evaluated on 2 participants in the TBI \& Blast group and 3 participants in the Blast Only group.

Air-conducted cervical vestibular evoked potential (cVEMP) inter-ear amplitude asymmetry ratio was used as a measure of otolith organ function (saccular-collic pathway). Inter-ear amplitude asymmetry ratio was calculated as: [(|L_P1-N1| - |R_P1-N1|)/ (|L_P1-N1| + |R_P1-N1|)] x100, where L_P1-N1 = peak-to-peak cVEMP amplitude of the left side and R_P1-N1 = peak-to-peak cVEMP amplitude of the right side. The amplitudes were calculated from cVEMP responses at a stimulus intensity of 120 dB peakSPL. The criterion for abnormal cVEMP was defined as an absent cVEMP or a corrected cVEMP amplitude asymmetry ratio greater than or equal to 40%, either of which would indicate a unilateral vestibular loss. A bilateral vestibular loss was indicated by absent cVEMPs bilaterally.

Outcome measures

Measure	TBI & Blast n=49 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI	Blast Only n=13 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI	TBI Only n=9 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure	Healthy Controls n=32 Participants Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure
Peripheral Vestibular Function (Saccular-collic Pathway): Cervical Vestibular Evoked Potential (cVEMP)	26.1 percentage of inter-ear asymmetry Standard Deviation 26.2	31.2 percentage of inter-ear asymmetry Standard Deviation 32.3	45.1 percentage of inter-ear asymmetry Standard Deviation 36.5	20.1 percentage of inter-ear asymmetry Standard Deviation 15.9

PRIMARY outcome

Timeframe: Up to 30 minutes (SHA phase is obtained simultaneously with SHA gain)

Population: Rotary chair slow harmonic acceleration (SHA) phase at 0.01 Hz was not calculated for 2 participants in the TBI \& Blast group and 1 participant in the Blast Only group. Phase at 0.01 Hz could not be calculated for individuals with bilateral vestibular loss.

Rotary chair slow harmonic acceleration (SHA) vestibulo-ocular reflex (VOR) phase at 0.01 Hz was used as a measure of peripheral vestibular function (VOR/horizontal semicircular canal). The phase is the timing difference between the velocity of head movement and the slow-phase eye velocity. This parameter is normalized for a full cycle of a sinusoid (360 degrees) and presented in an angular unit of degrees rather than a unit of time. For perfectly compensatory eye movements the phase is 0 degrees, meaning there is no difference between the actual eye velocity and the ideal VOR (by convention, degrees is added to the phase so that the comparison is based on the ideal VOR responses instead of the actual head motion).

Outcome measures

Measure	TBI & Blast n=49 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI	Blast Only n=15 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI	TBI Only n=9 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure	Healthy Controls n=32 Participants Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure
Rotary Chair Slow Harmonic Acceleration (SHA) Phase	41.3 degrees Standard Deviation 8.1	40.1 degrees Standard Deviation 6.4	40.1 degrees Standard Deviation 8.8	42.2 degrees Standard Deviation 8.3

PRIMARY outcome

Timeframe: Up to 20 minutes

Population: Ocular VEMP could not be obtained from 4 participants from the TBI \& Blast group.

Bone-conducted ocular vestibular evoked potential (oVEMP) inter-ear amplitude asymmetry ratio was used as a measure of otolith organ function (utricular-ocular pathway). Inter-ear amplitude asymmetry ratio was calculated as: [(|L_N1-P1| - |R_N1-P1|)/ (|L_N1-P1| + |R_N1-P1|)] x100, where L_N1-P1 = peak-to-peak oVEMP amplitude of the left eye/right ear and R_N1-P1 = peak-to-peak oVEMP amplitude of the right eye/left ear. The oVEMP is a contralateral response; therefore, recordings from the left eye reflect the response of the right ear and vice versa. The amplitudes were calculated from oVEMP responses at a stimulus intensity of 155 dB peakFL. The criterion for abnormal oVEMP was defined as an absent oVEMP or a corrected oVEMP amplitude asymmetry ratio greater than or equal to 40%, either of which would indicate a unilateral vestibular loss. A bilateral vestibular loss was indicated by absent oVEMPs bilaterally.

Outcome measures

Measure	TBI & Blast n=48 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI	Blast Only n=16 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI	TBI Only n=9 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure	Healthy Controls n=32 Participants Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure
Peripheral Vestibular Function (Utricular-ocular Pathway): Ocular Vestibular Evoked Potential (oVEMP)	22.0 percentage of inter-aural asymmetry Standard Deviation 21.2	15.7 percentage of inter-aural asymmetry Standard Deviation 14.3	39.1 percentage of inter-aural asymmetry Standard Deviation 28.3	18.0 percentage of inter-aural asymmetry Standard Deviation 14.6

SECONDARY outcome

Timeframe: 1 minute

Population: VOR gain during a visual fixation task and 0.16 Hz could not be obtained on 2 participants in the TBI \& Blast group and 3 participants in the Blast Only group.

Visual fixation suppression was used as a measure of central vestibular/CNS function. Visual fixation suppression is a measure of vestibulo-ocular reflex (VOR) gain obtained during visual fixation at 0.16 Hz slow harmonic acceleration on the rotary chair. VOR gain was defined as the ratio of the slow component velocity eye movement (output) to the velocity of the head movement (input). Visual fixation suppression was considered normal if VOR gain is suppressed > 50% with visual fixation compared to no fixation.

Outcome measures

Measure	TBI & Blast n=49 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI	Blast Only n=13 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI	TBI Only n=9 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure	Healthy Controls n=32 Participants Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure
Central Vestibular/Central Nervous System (CNS) Function: Visual Fixation Suppression	0.069 unitless Standard Deviation 0.049	0.058 unitless Standard Deviation 0.034	0.059 unitless Standard Deviation 0.034	0.065 unitless Standard Deviation 0.041

SECONDARY outcome

Timeframe: Up to 20 minutes

Population: The composite equilibrium score of the sensory organization test was not obtained for 4 participants in the TBI \& Blast group, 2 participants in the Blast Only group and 2 participants in the Healthy Control group.

This measure is the composite equilibrium score from six conditions of the sensory organization test obtained with the Neurocom Equitest. Results of the SOT were calculated based on maximum peak-to-peak anterior-posterior sway expressed as an equilibrium score ranging from 0 to 100, with 0 indicating loss of balance (i.e., required support of harness, took a step, touched walls for support or opened eyes in eyes closed conditions) and 100 indicating perfect stability. The outcome measure was the equilibrium composite score and was calculated by the software as the weighted average of the equilibrium scores for the six conditions. For ages 18-59 years, the normative value (mean - 1.67 SD) for the composite score is at least 70 (NeuroCom, 2011).

Outcome measures

Measure	TBI & Blast n=48 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI	Blast Only n=14 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI	TBI Only n=9 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure	Healthy Controls n=30 Participants Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure
Postural Stability: Sensory Organization Test (SOT)	65 units on a scale Standard Deviation 18.8	62 units on a scale Standard Deviation 19.3	61 units on a scale Standard Deviation 16.1	81 units on a scale Standard Deviation 5.1

SECONDARY outcome

Timeframe: Up to 10 minutes

The Dizziness Handicap Inventory (DHI) was used as a quality of life measure.The DHI measures the subject's self-perceived dizziness. The scale has 25 questions with 3 possible answers each: "Yes" = 4 points, "Sometimes" = 2 points, and "No" = 0 points. The minimum number of points that a subject can score is 0 and the maximum number of points is 100. The subject's self-perceived dizziness is reported as a percentage with a range of 0-100%, and is calculated by: subject's total number of points/maximum number of points (100) x 100%. The higher the score on the DHI, the worse a patient's self-perceived dizziness.

Outcome measures

Measure	TBI & Blast n=52 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI	Blast Only n=16 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI	TBI Only n=9 Participants OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure	Healthy Controls n=32 Participants Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure
Dizziness Handicap Inventory	48.7 score on a scale Standard Deviation 23.1	48.6 score on a scale Standard Deviation 25.5	41.6 score on a scale Standard Deviation 15.7	0 score on a scale Standard Deviation 0

Adverse Events

TBI & Blast

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Blast Only

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

TBI Only

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Healthy Controls

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Director of Vestibular Laboratory

James H. Quillen VA Medical Center

Phone: 423-926-1171

Email: faith.akin@va.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place