Trial Outcomes & Findings for Treatments of Mal de Debarquement Syndrome (MdDS) by Habituation of Velocity Storage (NCT NCT04213079)
NCT ID: NCT04213079
Last Updated: 2024-01-03
Results Overview
The overall severity of MdDS-related symptoms was subjectively reported on a single 11-point scale of 0-10, where the score 0 indicated no symptoms and 10 the most difficult of combined symptoms that the patient subject could imagine. Higher score indicates poorer health outcomes. Among the symptoms to consider were: brain fog, head pressure, fullness of ear, heavy head, headache, nausea, blurry vision, fatigue, sensitivity to fluorescent lights, scrolling of computer screen, sensitivity to smell, sensitivity to noise, walking on trampoline, sensation of gravitational pull up or down. Subjects were trained to estimate the level of symptoms to minimize inconsistency.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
47 participants
Primary outcome timeframe
During treatment (Day 1), Day 5, and 6 month follow up
Results posted on
2024-01-03
Participant Flow
Recruitment from April 2020 -July 2022 with first enrollment in June 2020; Patient volunteers with MdDS were recruited through various sources of referral and announcements posted on the Internet, including ClinicalTrials.gov (NCT04213079). Applicants seeking treatment were screened with an intake form, and each candidate's diagnosis of MdDS with an associable motion trigger was confirmed by a board-certified physician through a telephone interview when necessary.
Participant milestones
| Measure |
Vestibulo-ocular Reflex (VOR)
Treatment by re-adaptation of the vestibulo-ocular reflex (VOR) for participants with motion triggered MdDS
Re-adaptation of the vestibulo-ocular reflex: The VOR will be readapted by activating velocity storage with full-field optokinetic motion at 5°/s in a set direction while the head is oscillated with a set frequency and direction. The readaptation training will be conducted in repeated modules, each lasting for 1-5 min. The expected duration of daily sessions varies from 30 to 90 min. A day's session will be terminated if patient no longer feel symptoms of MdDS.
|
Habituation of Velocity Storage
Participants with motion triggered MdDS
Habituation of velocity storage of the vestibulo-ocular reflex: The central (velocity storage) time constant will be reduced by inducing cancellation of two velocity storage-mediated responses: OKN and the VOR. Sinusoidal rotation at 0.017 Hz (1 revolution/min) in darkness advances the slow phase eye velocity of the VOR by 32º. In contrast, the OKN at this frequency has no phase advancement. Thus, to counteract the VOR by OKN, the optokinetic stimulus should be set to 32º phase advance the out of phased head rotation stimulus. Since the conflict stimulus is expected to be overwhelming to patients at higher chair velocities, subjects will be first trained with a 10°/s stimulus. In a previous study, no complaints were reported when subjects were tested at such low velocities. Preliminary testing show signs of symptom improvement when the peak velocity reached 30°/s to 40°/s.
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
23
|
|
Overall Study
COMPLETED
|
24
|
21
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Vestibulo-ocular Reflex (VOR)
Treatment by re-adaptation of the vestibulo-ocular reflex (VOR) for participants with motion triggered MdDS
Re-adaptation of the vestibulo-ocular reflex: The VOR will be readapted by activating velocity storage with full-field optokinetic motion at 5°/s in a set direction while the head is oscillated with a set frequency and direction. The readaptation training will be conducted in repeated modules, each lasting for 1-5 min. The expected duration of daily sessions varies from 30 to 90 min. A day's session will be terminated if patient no longer feel symptoms of MdDS.
|
Habituation of Velocity Storage
Participants with motion triggered MdDS
Habituation of velocity storage of the vestibulo-ocular reflex: The central (velocity storage) time constant will be reduced by inducing cancellation of two velocity storage-mediated responses: OKN and the VOR. Sinusoidal rotation at 0.017 Hz (1 revolution/min) in darkness advances the slow phase eye velocity of the VOR by 32º. In contrast, the OKN at this frequency has no phase advancement. Thus, to counteract the VOR by OKN, the optokinetic stimulus should be set to 32º phase advance the out of phased head rotation stimulus. Since the conflict stimulus is expected to be overwhelming to patients at higher chair velocities, subjects will be first trained with a 10°/s stimulus. In a previous study, no complaints were reported when subjects were tested at such low velocities. Preliminary testing show signs of symptom improvement when the peak velocity reached 30°/s to 40°/s.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Vestibulo-ocular Reflex (VOR)
n=24 Participants
Treatment by re-adaptation of the vestibulo-ocular reflex (VOR) for participants with motion triggered MdDS
Re-adaptation of the vestibulo-ocular reflex: The VOR will be readapted by activating velocity storage with full-field optokinetic motion at 5°/s in a set direction while the head is oscillated with a set frequency and direction. The readaptation training will be conducted in repeated modules, each lasting for 1-5 min. The expected duration of daily sessions varies from 30 to 90 min. A day's session will be terminated if patient no longer feel symptoms of MdDS.
|
Habituation of Velocity Storage
n=21 Participants
Participants with motion triggered MdDS
Habituation of velocity storage of the vestibulo-ocular reflex: The central (velocity storage) time constant will be reduced by inducing cancellation of two velocity storage-mediated responses: OKN and the VOR. Sinusoidal rotation at 0.017 Hz (1 revolution/min) in darkness advances the slow phase eye velocity of the VOR by 32º. In contrast, the OKN at this frequency has no phase advancement. Thus, to counteract the VOR by OKN, the optokinetic stimulus should be set to 32º phase advance the out of phased head rotation stimulus. Since the conflict stimulus is expected to be overwhelming to patients at higher chair velocities, subjects will be first trained with a 10°/s stimulus. In a previous study, no complaints were reported when subjects were tested at such low velocities. Preliminary testing show signs of symptom improvement when the peak velocity reached 30°/s to 40°/s.
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
47.4 years
STANDARD_DEVIATION 13.9 • n=24 Participants
|
46.7 years
STANDARD_DEVIATION 14.2 • n=21 Participants
|
47.1 years
STANDARD_DEVIATION 14.0 • n=45 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=24 Participants
|
16 Participants
n=21 Participants
|
38 Participants
n=45 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=24 Participants
|
5 Participants
n=21 Participants
|
7 Participants
n=45 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
PRIMARY outcome
Timeframe: During treatment (Day 1), Day 5, and 6 month follow upThe overall severity of MdDS-related symptoms was subjectively reported on a single 11-point scale of 0-10, where the score 0 indicated no symptoms and 10 the most difficult of combined symptoms that the patient subject could imagine. Higher score indicates poorer health outcomes. Among the symptoms to consider were: brain fog, head pressure, fullness of ear, heavy head, headache, nausea, blurry vision, fatigue, sensitivity to fluorescent lights, scrolling of computer screen, sensitivity to smell, sensitivity to noise, walking on trampoline, sensation of gravitational pull up or down. Subjects were trained to estimate the level of symptoms to minimize inconsistency.
Outcome measures
| Measure |
Vestibulo-ocular Reflex (VOR)
n=24 Participants
Treatment by re-adaptation of the vestibulo-ocular reflex (VOR) for participants with motion triggered MdDS
Re-adaptation of the vestibulo-ocular reflex: The VOR will be readapted by activating velocity storage with full-field optokinetic motion at 5°/s in a set direction while the head is oscillated with a set frequency and direction. The readaptation training will be conducted in repeated modules, each lasting for 1-5 min. The expected duration of daily sessions varies from 30 to 90 min. A day's session will be terminated if patient no longer feel symptoms of MdDS.
|
Habituation of Velocity Storage
n=21 Participants
Participants with motion triggered MdDS
Habituation of velocity storage of the vestibulo-ocular reflex: The central (velocity storage) time constant will be reduced by inducing cancellation of two velocity storage-mediated responses: OKN and the VOR. Sinusoidal rotation at 0.017 Hz (1 revolution/min) in darkness advances the slow phase eye velocity of the VOR by 32º. In contrast, the OKN at this frequency has no phase advancement. Thus, to counteract the VOR by OKN, the optokinetic stimulus should be set to 32º phase advance the out of phased head rotation stimulus. Since the conflict stimulus is expected to be overwhelming to patients at higher chair velocities, subjects will be first trained with a 10°/s stimulus. In a previous study, no complaints were reported when subjects were tested at such low velocities. Preliminary testing show signs of symptom improvement when the peak velocity reached 30°/s to 40°/s.
|
|---|---|---|
|
Subjective Symptoms Self-report of Overall Severity
Day 1
|
5.2 score on a scale
Standard Deviation 1.9
|
5.2 score on a scale
Standard Deviation 1.9
|
|
Subjective Symptoms Self-report of Overall Severity
Day 5
|
3.2 score on a scale
Standard Deviation 2.1
|
2.1 score on a scale
Standard Deviation 1.7
|
|
Subjective Symptoms Self-report of Overall Severity
6 month follow up
|
2.9 score on a scale
Standard Deviation 2.0
|
3.4 score on a scale
Standard Deviation 2.2
|
SECONDARY outcome
Timeframe: Baseline and 6 month follow upVisual Vertigo Analogue Scale. There are 9 separate visual analogue scales to rate intensity of visual vertigo provoking situation. Each scale is on a 0-10 cm line. Full scale from 0-10. Higher score represents more dizziness.
Outcome measures
| Measure |
Vestibulo-ocular Reflex (VOR)
n=24 Participants
Treatment by re-adaptation of the vestibulo-ocular reflex (VOR) for participants with motion triggered MdDS
Re-adaptation of the vestibulo-ocular reflex: The VOR will be readapted by activating velocity storage with full-field optokinetic motion at 5°/s in a set direction while the head is oscillated with a set frequency and direction. The readaptation training will be conducted in repeated modules, each lasting for 1-5 min. The expected duration of daily sessions varies from 30 to 90 min. A day's session will be terminated if patient no longer feel symptoms of MdDS.
|
Habituation of Velocity Storage
n=21 Participants
Participants with motion triggered MdDS
Habituation of velocity storage of the vestibulo-ocular reflex: The central (velocity storage) time constant will be reduced by inducing cancellation of two velocity storage-mediated responses: OKN and the VOR. Sinusoidal rotation at 0.017 Hz (1 revolution/min) in darkness advances the slow phase eye velocity of the VOR by 32º. In contrast, the OKN at this frequency has no phase advancement. Thus, to counteract the VOR by OKN, the optokinetic stimulus should be set to 32º phase advance the out of phased head rotation stimulus. Since the conflict stimulus is expected to be overwhelming to patients at higher chair velocities, subjects will be first trained with a 10°/s stimulus. In a previous study, no complaints were reported when subjects were tested at such low velocities. Preliminary testing show signs of symptom improvement when the peak velocity reached 30°/s to 40°/s.
|
|---|---|---|
|
Visual Vertigo Analogue Scale (VVAS)
Baseline
|
4.8 score on a scale
Standard Deviation 2.0
|
4.4 score on a scale
Standard Deviation 2.3
|
|
Visual Vertigo Analogue Scale (VVAS)
6 month follow up
|
2.5 score on a scale
Standard Deviation 2.1
|
2.6 score on a scale
Standard Deviation 2.2
|
SECONDARY outcome
Timeframe: Baseline and 6 month follow upPhysical, emotional, and functional disability related to MdDS will be assessed with DHI. DHI is a 25-item self report questionnaire, total score range from 0 to 100, with higher score indicating more perceived disability.
Outcome measures
| Measure |
Vestibulo-ocular Reflex (VOR)
n=24 Participants
Treatment by re-adaptation of the vestibulo-ocular reflex (VOR) for participants with motion triggered MdDS
Re-adaptation of the vestibulo-ocular reflex: The VOR will be readapted by activating velocity storage with full-field optokinetic motion at 5°/s in a set direction while the head is oscillated with a set frequency and direction. The readaptation training will be conducted in repeated modules, each lasting for 1-5 min. The expected duration of daily sessions varies from 30 to 90 min. A day's session will be terminated if patient no longer feel symptoms of MdDS.
|
Habituation of Velocity Storage
n=21 Participants
Participants with motion triggered MdDS
Habituation of velocity storage of the vestibulo-ocular reflex: The central (velocity storage) time constant will be reduced by inducing cancellation of two velocity storage-mediated responses: OKN and the VOR. Sinusoidal rotation at 0.017 Hz (1 revolution/min) in darkness advances the slow phase eye velocity of the VOR by 32º. In contrast, the OKN at this frequency has no phase advancement. Thus, to counteract the VOR by OKN, the optokinetic stimulus should be set to 32º phase advance the out of phased head rotation stimulus. Since the conflict stimulus is expected to be overwhelming to patients at higher chair velocities, subjects will be first trained with a 10°/s stimulus. In a previous study, no complaints were reported when subjects were tested at such low velocities. Preliminary testing show signs of symptom improvement when the peak velocity reached 30°/s to 40°/s.
|
|---|---|---|
|
Dizziness Handicap Inventory (DHI) Questionnaire
Baseline
|
52.1 score on a scale
Standard Deviation 17.3
|
47.2 score on a scale
Standard Deviation 16.1
|
|
Dizziness Handicap Inventory (DHI) Questionnaire
6 month follow up
|
35.3 score on a scale
Standard Deviation 19.5
|
32.1 score on a scale
Standard Deviation 18.6
|
SECONDARY outcome
Timeframe: Baseline and Day 5The vestibulo-ocular reflex (VOR) is a class of reflex eye movement that counters head movement to stabilize vision. A perfect stabilization occurs when the velocity of the retinal image slip is zero, i.e. when the ratio, or gain, of the eye rotation speed to the head rotation speed is one. The VOR is a fast reflex whose direct pathway consists of a three-neuron arc, but also has parallel, indirect pathways that allow integration of signals from the peripheral vestibular organs with those of other sensory modalities such as vision and proprioception to modulate the eye movement response. The gain of the direct VOR pathway is the ratio of the eye rotation speed to the head rotation speed at the onset of head rotation, and is a unitless measure.
Outcome measures
| Measure |
Vestibulo-ocular Reflex (VOR)
n=24 Participants
Treatment by re-adaptation of the vestibulo-ocular reflex (VOR) for participants with motion triggered MdDS
Re-adaptation of the vestibulo-ocular reflex: The VOR will be readapted by activating velocity storage with full-field optokinetic motion at 5°/s in a set direction while the head is oscillated with a set frequency and direction. The readaptation training will be conducted in repeated modules, each lasting for 1-5 min. The expected duration of daily sessions varies from 30 to 90 min. A day's session will be terminated if patient no longer feel symptoms of MdDS.
|
Habituation of Velocity Storage
n=21 Participants
Participants with motion triggered MdDS
Habituation of velocity storage of the vestibulo-ocular reflex: The central (velocity storage) time constant will be reduced by inducing cancellation of two velocity storage-mediated responses: OKN and the VOR. Sinusoidal rotation at 0.017 Hz (1 revolution/min) in darkness advances the slow phase eye velocity of the VOR by 32º. In contrast, the OKN at this frequency has no phase advancement. Thus, to counteract the VOR by OKN, the optokinetic stimulus should be set to 32º phase advance the out of phased head rotation stimulus. Since the conflict stimulus is expected to be overwhelming to patients at higher chair velocities, subjects will be first trained with a 10°/s stimulus. In a previous study, no complaints were reported when subjects were tested at such low velocities. Preliminary testing show signs of symptom improvement when the peak velocity reached 30°/s to 40°/s.
|
|---|---|---|
|
VOR Direct Pathway Gain
Baseline
|
0.53 ratio
Standard Deviation 0.13
|
0.42 ratio
Standard Deviation 0.10
|
|
VOR Direct Pathway Gain
6 month follow up
|
0.45 ratio
Standard Deviation 0.14
|
0.47 ratio
Standard Deviation 0.08
|
SECONDARY outcome
Timeframe: Baseline and Day 5The velocity storage mechanism is an indirect component of the VOR that facilitates the reflex by storing and releasing signals related to head rotation, for example by prolonging the eye movement response beyond the peripheral vestibular activity during head movement and generating similar eye movement response to rotational cues provided by other sensory modalities. The time constant of this indirect VOR pathway is the rate of charging/discharging in the exponential ideation of its behavior, measured in seconds, estimated from the profile of eye rotation speed during prolonged whole-body rotation that is the combination of the contributions from the direct and indirect pathways.
Outcome measures
| Measure |
Vestibulo-ocular Reflex (VOR)
n=24 Participants
Treatment by re-adaptation of the vestibulo-ocular reflex (VOR) for participants with motion triggered MdDS
Re-adaptation of the vestibulo-ocular reflex: The VOR will be readapted by activating velocity storage with full-field optokinetic motion at 5°/s in a set direction while the head is oscillated with a set frequency and direction. The readaptation training will be conducted in repeated modules, each lasting for 1-5 min. The expected duration of daily sessions varies from 30 to 90 min. A day's session will be terminated if patient no longer feel symptoms of MdDS.
|
Habituation of Velocity Storage
n=21 Participants
Participants with motion triggered MdDS
Habituation of velocity storage of the vestibulo-ocular reflex: The central (velocity storage) time constant will be reduced by inducing cancellation of two velocity storage-mediated responses: OKN and the VOR. Sinusoidal rotation at 0.017 Hz (1 revolution/min) in darkness advances the slow phase eye velocity of the VOR by 32º. In contrast, the OKN at this frequency has no phase advancement. Thus, to counteract the VOR by OKN, the optokinetic stimulus should be set to 32º phase advance the out of phased head rotation stimulus. Since the conflict stimulus is expected to be overwhelming to patients at higher chair velocities, subjects will be first trained with a 10°/s stimulus. In a previous study, no complaints were reported when subjects were tested at such low velocities. Preliminary testing show signs of symptom improvement when the peak velocity reached 30°/s to 40°/s.
|
|---|---|---|
|
VOR Indirect Pathway Time Constant
Baseline
|
16.6 seconds
Standard Deviation 3.9
|
15.0 seconds
Standard Deviation 4.0
|
|
VOR Indirect Pathway Time Constant
Day 5
|
16.0 seconds
Standard Deviation 5.4
|
15.6 seconds
Standard Deviation 4.5
|
SECONDARY outcome
Timeframe: Baseline and Day 5The gain of the indirect VOR pathway is the term that determines the contribution of velocity storage to the profile of eye rotation speed during prolonged whole-body rotation. The measure is normalized to the head rotation velocity and is thus unitless.
Outcome measures
| Measure |
Vestibulo-ocular Reflex (VOR)
n=24 Participants
Treatment by re-adaptation of the vestibulo-ocular reflex (VOR) for participants with motion triggered MdDS
Re-adaptation of the vestibulo-ocular reflex: The VOR will be readapted by activating velocity storage with full-field optokinetic motion at 5°/s in a set direction while the head is oscillated with a set frequency and direction. The readaptation training will be conducted in repeated modules, each lasting for 1-5 min. The expected duration of daily sessions varies from 30 to 90 min. A day's session will be terminated if patient no longer feel symptoms of MdDS.
|
Habituation of Velocity Storage
n=21 Participants
Participants with motion triggered MdDS
Habituation of velocity storage of the vestibulo-ocular reflex: The central (velocity storage) time constant will be reduced by inducing cancellation of two velocity storage-mediated responses: OKN and the VOR. Sinusoidal rotation at 0.017 Hz (1 revolution/min) in darkness advances the slow phase eye velocity of the VOR by 32º. In contrast, the OKN at this frequency has no phase advancement. Thus, to counteract the VOR by OKN, the optokinetic stimulus should be set to 32º phase advance the out of phased head rotation stimulus. Since the conflict stimulus is expected to be overwhelming to patients at higher chair velocities, subjects will be first trained with a 10°/s stimulus. In a previous study, no complaints were reported when subjects were tested at such low velocities. Preliminary testing show signs of symptom improvement when the peak velocity reached 30°/s to 40°/s.
|
|---|---|---|
|
VOR Indirect Pathway Coupling Gain
Baseline
|
0.102 ratio
Standard Deviation 0.022
|
0.093 ratio
Standard Deviation 0.030
|
|
VOR Indirect Pathway Coupling Gain
Day 5
|
0.080 ratio
Standard Deviation 0.033
|
0.099 ratio
Standard Deviation 0.027
|
Adverse Events
Vestibulo-ocular Reflex (VOR)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Habituation of Velocity Storage
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
Sergei Yakushin
Icahn School of Medicine at Mount Sinai
Phone: 212-241-9349
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place