Mal de Debarquement Syndrome (MdDS)
Conditions
Keywords
Mal de Debarquement Syndrome, Motion Sickness, body rocking, body swaying, Habituation of velocity storage
Brief summary
Mal de Debarquement Syndrome (MdDS) is an under-recognized but nevertheless common balance disorder, which in most cases occurs after exposure to prolonged passive motion. The current treatment approaches focus on reducing symptoms, but they can be retriggered. This project aims to shift the focus of MdDS treatment to permanently eliminating the symptom trigger while also minimizing symptoms.
Detailed description
Mal de Debarquement Syndrome (MdDS) is an under-recognized but nevertheless common balance disorder, primarily manifested by constant self-motion sensations consisting of rocking/swaying or gravitational pull of the body, which are accompanied by fatigue, migraine, hypersensitivity to light/noise/crowds, visually induced dizziness, and cognitive dysfunctions. As the name implies (disembarkation sickness), in most cases MdDS occurs after exposure to prolonged passive motion, specified as motion-triggered (MT) MdDS. However, the symptoms of MdDS can also occur without a motion trigger, termed as spontaneous MdDS. MdDS is debilitating and entails various mental health issues, such as suicidal thoughts, depression, and anxiety. Treatments for this disorder are still limited, as the specific underlying pathophysiology remains unclear. Recently, the team developed the first treatment method that can safely and effectively ease MdDS symptoms in the majority of patients via readaptation of the vestibulo-ocular reflex (VOR). The hypothesis underlying this treatment is that MdDS is caused by maladaptation of the functional component of the VOR called velocity storage, whose readaptation can be stimulated by exposure to whole-field visual motion coupled with head tilts. Over the past several years, more than 500 patients from around the world have been treated with this method. The success rate immediately after this treatment is 75% for MT MdDS, but some patients report return of symptoms after subsequent flights or prolonged car rides. Thus, the effectiveness of the current MdDS treatment protocol can depend on a serious practical limitation of needing to permanently avoid transportation. Building on the previous hypothesis of velocity storage maladaptation, the study team currently hypothesizes that another method, based on the reduction (habituation) of the velocity storage, can also resolve MdDS symptoms. Velocity storage can be greatly habituated within 4-5 days using a protocol previously developed in the study team's laboratory to reduce susceptibility to motion sickness. Preliminary data support the application of this protocol to MdDS. Moreover, since animal-based research suggests that velocity storage habituation is permanently retained, the study team further hypothesizes that this new treatment method yields robust long-term outcomes. In this project, 50 MT MdDS patients with otherwise normal vestibular and neurological functions will be randomly assigned into two groups, one to be treated by velocity storage habituation and the other by readaptation. Patients will be followed up for 6 months. Based on the preliminary data, the study team expects both groups to yield similar initial success rates for symptom improvement. However, the study team expects the group undergoing the habituation protocol to better retain the initial treatment impact in the long term. This project will significantly impact the MdDS treatment practice. The current approach focuses on reducing symptoms, but they can be retriggered by another prolonged exposure to passive motion. The habituation approach on the other hand focuses on permanently minimizing the symptom trigger while also minimizing symptoms. This project will also increase the current understanding of recurrent MdDS.
Interventions
DEVICEre-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.
DEVICEHabituation 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.
Sponsors
National Institute on Deafness and Other Communication Disorders (NIDCD)
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
In this project, 50 motion triggered MdDS patients with otherwise normal vestibular and neurological functions will be randomly assigned into two groups, one to be treated by velocity storage habituation and the other by readaptation. Patients will be followed up for 6 months. Based on the preliminary data, we expect both groups to yield similar initial success rates for symptom improvement.
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
\- Age 18-78.
Exclusion criteria
\- Patient with serious spinal, neck and legs injuries will be excluded, since postural ability is essential for both treatments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Symptoms Self-report of Overall Severity | During treatment (Day 1), Day 5, and 6 month follow up | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Vertigo Analogue Scale (VVAS) | Baseline and 6 month follow up | Visual 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. |
| Dizziness Handicap Inventory (DHI) Questionnaire | Baseline and 6 month follow up | Physical, 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. |
| VOR Direct Pathway Gain | Baseline and Day 5 | The 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. |
| VOR Indirect Pathway Time Constant | Baseline and Day 5 | The 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. |
| VOR Indirect Pathway Coupling Gain | Baseline and Day 5 | The 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. |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 24 |
| 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. | 21 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | Vestibulo-ocular Reflex (VOR) | Habituation of Velocity Storage | Total |
|---|---|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 13.9 | 46.7 years STANDARD_DEVIATION 14.2 | 47.1 years STANDARD_DEVIATION 14 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 22 Participants | 16 Participants | 38 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 21 |
| other Total, other adverse events | 0 / 24 | 0 / 21 |
| serious Total, serious adverse events | 0 / 24 | 0 / 21 |
Outcome results
Primary
Subjective Symptoms Self-report of Overall Severity
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.
Time frame: During treatment (Day 1), Day 5, and 6 month follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vestibulo-ocular Reflex (VOR) | Subjective Symptoms Self-report of Overall Severity | Day 1 | 5.2 score on a scale | Standard Deviation 1.9 |
| Vestibulo-ocular Reflex (VOR) | Subjective Symptoms Self-report of Overall Severity | Day 5 | 3.2 score on a scale | Standard Deviation 2.1 |
| Vestibulo-ocular Reflex (VOR) | Subjective Symptoms Self-report of Overall Severity | 6 month follow up | 2.9 score on a scale | Standard Deviation 2 |
| Habituation of Velocity Storage | Subjective Symptoms Self-report of Overall Severity | Day 5 | 2.1 score on a scale | Standard Deviation 1.7 |
| Habituation of Velocity Storage | Subjective Symptoms Self-report of Overall Severity | Day 1 | 5.2 score on a scale | Standard Deviation 1.9 |
| Habituation of Velocity Storage | Subjective Symptoms Self-report of Overall Severity | 6 month follow up | 3.4 score on a scale | Standard Deviation 2.2 |
Secondary
Dizziness Handicap Inventory (DHI) Questionnaire
Physical, 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.
Time frame: Baseline and 6 month follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vestibulo-ocular Reflex (VOR) | Dizziness Handicap Inventory (DHI) Questionnaire | Baseline | 52.1 score on a scale | Standard Deviation 17.3 |
| Vestibulo-ocular Reflex (VOR) | Dizziness Handicap Inventory (DHI) Questionnaire | 6 month follow up | 35.3 score on a scale | Standard Deviation 19.5 |
| Habituation of Velocity Storage | Dizziness Handicap Inventory (DHI) Questionnaire | Baseline | 47.2 score on a scale | Standard Deviation 16.1 |
| Habituation of Velocity Storage | Dizziness Handicap Inventory (DHI) Questionnaire | 6 month follow up | 32.1 score on a scale | Standard Deviation 18.6 |
Secondary
Visual Vertigo Analogue Scale (VVAS)
Visual 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.
Time frame: Baseline and 6 month follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vestibulo-ocular Reflex (VOR) | Visual Vertigo Analogue Scale (VVAS) | Baseline | 4.8 score on a scale | Standard Deviation 2 |
| Vestibulo-ocular Reflex (VOR) | Visual Vertigo Analogue Scale (VVAS) | 6 month follow up | 2.5 score on a scale | Standard Deviation 2.1 |
| Habituation of Velocity Storage | Visual Vertigo Analogue Scale (VVAS) | Baseline | 4.4 score on a scale | Standard Deviation 2.3 |
| Habituation of Velocity Storage | Visual Vertigo Analogue Scale (VVAS) | 6 month follow up | 2.6 score on a scale | Standard Deviation 2.2 |
Secondary
VOR Direct Pathway Gain
The 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.
Time frame: Baseline and Day 5
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vestibulo-ocular Reflex (VOR) | VOR Direct Pathway Gain | 6 month follow up | 0.45 ratio | Standard Deviation 0.14 |
| Vestibulo-ocular Reflex (VOR) | VOR Direct Pathway Gain | Baseline | 0.53 ratio | Standard Deviation 0.13 |
| Habituation of Velocity Storage | VOR Direct Pathway Gain | Baseline | 0.42 ratio | Standard Deviation 0.1 |
| Habituation of Velocity Storage | VOR Direct Pathway Gain | 6 month follow up | 0.47 ratio | Standard Deviation 0.08 |
Secondary
VOR Indirect Pathway Coupling Gain
The 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.
Time frame: Baseline and Day 5
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vestibulo-ocular Reflex (VOR) | VOR Indirect Pathway Coupling Gain | Baseline | 0.102 ratio | Standard Deviation 0.022 |
| Vestibulo-ocular Reflex (VOR) | VOR Indirect Pathway Coupling Gain | Day 5 | 0.080 ratio | Standard Deviation 0.033 |
| Habituation of Velocity Storage | VOR Indirect Pathway Coupling Gain | Baseline | 0.093 ratio | Standard Deviation 0.03 |
| Habituation of Velocity Storage | VOR Indirect Pathway Coupling Gain | Day 5 | 0.099 ratio | Standard Deviation 0.027 |
Secondary
VOR Indirect Pathway Time Constant
The 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.
Time frame: Baseline and Day 5
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vestibulo-ocular Reflex (VOR) | VOR Indirect Pathway Time Constant | Baseline | 16.6 seconds | Standard Deviation 3.9 |
| Vestibulo-ocular Reflex (VOR) | VOR Indirect Pathway Time Constant | Day 5 | 16.0 seconds | Standard Deviation 5.4 |
| Habituation of Velocity Storage | VOR Indirect Pathway Time Constant | Baseline | 15.0 seconds | Standard Deviation 4 |
| Habituation of Velocity Storage | VOR Indirect Pathway Time Constant | Day 5 | 15.6 seconds | Standard Deviation 4.5 |