Mal de Debarquement Syndrome
Conditions
Keywords
MdDS, TMS, fMRI, EEG
Brief summary
The goal of this study is to determine whether external neuromodulation using repetitive transcranial magnetic stimulation (rTMS) can reduce the perception of self-motion that is experienced by individuals with mal de debarquement syndrome (MdDS). Mal de debarquement is translated as the sickness of disembarkment, and refers to the chronic feeling of rocking dizziness that occurs after exposure to passive motion. Treatment for MdDS is limited and morbidity is high. The goal of the study is to determine whether rTMS can suppress the rocking dizziness of MdDS.
Detailed description
Participants will maintain web-based diaries of their symptoms for two weeks prior to treatment with rTMS. Up to 20 treatments with rTMS with either anatomically or functionally determined targets will be administered. Post treatment diaries will continue for up to 12 weeks after rTMS administration.
Interventions
DEVICETranscranial Magnetic Stimulation
A form of external neuromodulation using pulsatile magnetic fields on the surface of the head.
Sponsors
University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This was an N-of-1 pilot study in which all participants received one session of each of 3 targets and chose which of the 3 led to the most acute reduction in intensity of rocking. The participants were treated with the target that they chose and then completed post stimulation diaries.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years old 2. Willing and capable of interacting with the informed consent process 3. Primary disorder being a persistent rocking dizziness triggered by passive motion such as from water, land, or air travel and with no other central nervous system or peripheral vestibular disorder determined after appropriate evaluation.
Exclusion criteria
1. Subjects who cannot comply with study conditions. 2. Active psychiatric condition such as mania or psychosis 3. Unstable medical condition 4. Implanted metal anywhere in the body (infusion pumps, pacemakers, metal or shrapnel in the body, deep brain stimulators, aneurysm clips, metal prostheses, joints, rods or plates). Dental fillings are acceptable. 5. Personal history of seizures or a first-degree relative with epilepsy 6. Medications known to lower seizure threshold such as: typical (high-potency) neuroleptics and tricyclic antidepressants: Subjects who take one or a combination of the following drugs will be excluded: imipramine, amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine. clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, cocaine (including MDMA, ecstasy), phencyclidine (PCP, angel's dust), ketamine, gamma-hydroxybutyrate (GHB), theophylline, haloperidol, fluphenazine, bupropion. 7. Pregnancy or planning to become pregnant during study enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dizziness Handicap Inventory | 10 weeks (4 pre stimulation + 6 post stimulation) | The Dizziness Handicap Inventory is a widely used measure of subjective dizziness in which 25 questions of dizziness inducing events are rated on a scale of 0-2-4. The maximum number of points is 100 points which are divided into the following levels: 16-34 Points (mild handicap), 36-52 Points (moderate handicap), 54+ Points (severe handicap). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mal de Debarquement Balance Rating Scale | 10 weeks (4 pre stimulation + 6 post stimulation) | The MdDS Balance Rating Scale is a 10-point scale inquiring about the severity of rocking vertigo in which 1 means no rocking and 10 is so severe that standing is not possible. A level of 6 indicates that gait is impaired due to the severity of rocking. |
| Hospital Anxiety and Depression Scale | 10 weeks (4 pre stimulation + 6 post stimulation) | The Hospital Anxiety and Depression Scale is a widely used scale that inquires about anxiety and depression symptoms with 14 questions divided into 7 questions about anxiety and 7 questions about depression. Each item is rated from 0-3 per item yielding a maximum of 21 points per item. Each subscale is rated as follows: 0-7 (Normal), 8-10 (Borderline), 11-21 (Abnormal). |
Countries
United States
Participant flow
Recruitment details
August 15 to July 2017
Pre-assignment details
All enrolled participants were included. This was an N-of-1 study so all participants received one session each of each target. Two participants were excluded prior to enrollment (one due to medical illness before she selected a target, one due to side effects from all targets and not being treated on the protocol).
Participants by arm
| Arm | Count |
|---|---|
| Target 1: Occipital Cortex After determination of the motor threshold, the TMS coil will be positioned at predetermined locations over the brain using MRI guidance and a frameless stereotaxy system. A train of continuous theta burst mode will be delivered at the midline occipital cortex, with the brain locations determined by MRI and real-time neuronavigation.
Transcranial Magnetic Stimulation: A form of external neuromodulation using pulsatile magnetic fields on the surface of the head. | 10 |
| Target 2: Cerebellar Vermis An active comparator not at the target of interest will be used for the study. A train of continuous theta burst mode will be delivered at the midline cerebellar vermis, with the brain locations determined by MRI and real-time neuronavigation.
Transcranial Magnetic Stimulation: A form of external neuromodulation using pulsatile magnetic fields on the surface of the head. | 9 |
| Target 3: Cerebellar Hemisphere An active comparator not at the target of interest will be used for the study. A train of continuous theta burst mode will be delivered at the cerebellar hemisphere with the brain locations determined by MRI and real-time neuronavigation.
Transcranial Magnetic Stimulation: A form of external neuromodulation using pulsatile magnetic fields on the surface of the head. | 5 |
| Total | 24 |
Baseline characteristics
| Characteristic | Target 2: Cerebellar Vermis | Total | Target 1: Occipital Cortex | Target 3: Cerebellar Hemisphere |
|---|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 11.5 | 51.9 years STANDARD_DEVIATION 12.4 | 55.1 years STANDARD_DEVIATION 11.1 | 42.6 years STANDARD_DEVIATION 14 |
| Dizziness Handicap Inventory Total | 51.1 units on a scale STANDARD_DEVIATION 13 | 49.2 units on a scale STANDARD_DEVIATION 12.9 | 46.2 units on a scale STANDARD_DEVIATION 13.7 | 51.6 units on a scale STANDARD_DEVIATION 12.6 |
| Hospital Anxiety and Depression Scale-Anxiety | 6.3 units on a scale STANDARD_DEVIATION 3.8 | 6.9 units on a scale STANDARD_DEVIATION 3.3 | 6.2 units on a scale STANDARD_DEVIATION 2.6 | 9.4 units on a scale STANDARD_DEVIATION 3.2 |
| Hospital Anxiety and Depression Scale-Depression | 8.0 units on a scale STANDARD_DEVIATION 3.2 | 7.9 units on a scale STANDARD_DEVIATION 3.4 | 7.0 units on a scale STANDARD_DEVIATION 3.4 | 9.6 units on a scale STANDARD_DEVIATION 3.8 |
| Mal de Debarquement Balance Rating Scale | 5.2 units on a scale STANDARD_DEVIATION 0.8 | 4.8 units on a scale STANDARD_DEVIATION 1.2 | 4.6 units on a scale STANDARD_DEVIATION 1.3 | 4.4 units on a scale STANDARD_DEVIATION 1.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 24 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Female | 9 Participants | 24 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 | 0 / 5 |
| other Total, other adverse events | 0 / 10 | 0 / 9 | 0 / 5 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 | 0 / 5 |
Outcome results
Primary
Dizziness Handicap Inventory
The Dizziness Handicap Inventory is a widely used measure of subjective dizziness in which 25 questions of dizziness inducing events are rated on a scale of 0-2-4. The maximum number of points is 100 points which are divided into the following levels: 16-34 Points (mild handicap), 36-52 Points (moderate handicap), 54+ Points (severe handicap).
Time frame: 10 weeks (4 pre stimulation + 6 post stimulation)
Population: The median of the 4 pre-stimulation scores was used as the baseline. The difference between this number and the post-stimulation scores were calculated for each participant. The mean and standard deviation for the change in scores from the median of the baseline scores is presented for each treatment group for scores reported immediately after TMS and 6 weeks post TMS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Occipital Transcranial Magnetic Stimulation | Dizziness Handicap Inventory | Immediate change | -17.5 score on a scale | Standard Deviation 10.3 |
| Occipital Transcranial Magnetic Stimulation | Dizziness Handicap Inventory | 6 week change | -10.1 score on a scale | Standard Deviation 18 |
| Vermis Transcranial Magnetic Stimulation | Dizziness Handicap Inventory | Immediate change | -3.7 score on a scale | Standard Deviation 10.6 |
| Vermis Transcranial Magnetic Stimulation | Dizziness Handicap Inventory | 6 week change | -9.7 score on a scale | Standard Deviation 12.2 |
| Cerebellar Hemisphere Control Transcranial Magnetic Stimulation | Dizziness Handicap Inventory | Immediate change | -8.4 score on a scale | Standard Deviation 14.4 |
| Cerebellar Hemisphere Control Transcranial Magnetic Stimulation | Dizziness Handicap Inventory | 6 week change | -4.0 score on a scale | Standard Deviation 9 |
Comparison: This was an N-of-1 pilot study in which all participants received one session of each of 3 targets and chose which of the 3 led to the most acute reduction in intensity of rocking. The participants were treated with the target that they chose and then completed post stimulation diaries.p-value: 0.0439ANOVA
Secondary
Hospital Anxiety and Depression Scale
The Hospital Anxiety and Depression Scale is a widely used scale that inquires about anxiety and depression symptoms with 14 questions divided into 7 questions about anxiety and 7 questions about depression. Each item is rated from 0-3 per item yielding a maximum of 21 points per item. Each subscale is rated as follows: 0-7 (Normal), 8-10 (Borderline), 11-21 (Abnormal).
Time frame: 10 weeks (4 pre stimulation + 6 post stimulation)
Population: The median of the 4 pre-stimulation scores was used as the baseline. The difference between this number and the post-stimulation scores were calculated for each participant. The mean and standard deviation for the change in scores from the median of the baseline scores is presented for each treatment group for scores reported immediately after TMS and 6 weeks post TMS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Occipital Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | Immediate change-Anxiety | -2.5 score on a scale | Standard Deviation 2.4 |
| Occipital Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | 6 week change-Anxiety | -2.2 score on a scale | Standard Deviation 2.4 |
| Occipital Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | Immediate change-Depression | -2.4 score on a scale | Standard Deviation 2.5 |
| Occipital Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | 6 week change-Depression | -1.7 score on a scale | Standard Deviation 4.3 |
| Vermis Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | 6 week change-Depression | -1.4 score on a scale | Standard Deviation 3.7 |
| Vermis Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | Immediate change-Anxiety | 0.8 score on a scale | Standard Deviation 5.3 |
| Vermis Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | Immediate change-Depression | -0.4 score on a scale | Standard Deviation 4.9 |
| Vermis Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | 6 week change-Anxiety | -1.6 score on a scale | Standard Deviation 3.5 |
| Cerebellar Hemisphere Control Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | 6 week change-Depression | 0.4 score on a scale | Standard Deviation 1 |
| Cerebellar Hemisphere Control Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | 6 week change-Anxiety | -0.4 score on a scale | Standard Deviation 1.9 |
| Cerebellar Hemisphere Control Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | Immediate change-Depression | 1.4 score on a scale | Standard Deviation 2.5 |
| Cerebellar Hemisphere Control Transcranial Magnetic Stimulation | Hospital Anxiety and Depression Scale | Immediate change-Anxiety | -0.2 score on a scale | Standard Deviation 2.6 |
Comparison: This was an N-of-1 pilot study in which all participants received one session of each of 3 targets and chose which of the 3 led to the most acute reduction in intensity of rocking. The participants were treated with the target that they chose and then completed post stimulation diaries.p-value: 0.1754ANOVA
Secondary
Mal de Debarquement Balance Rating Scale
The MdDS Balance Rating Scale is a 10-point scale inquiring about the severity of rocking vertigo in which 1 means no rocking and 10 is so severe that standing is not possible. A level of 6 indicates that gait is impaired due to the severity of rocking.
Time frame: 10 weeks (4 pre stimulation + 6 post stimulation)
Population: The median of the 4 pre-stimulation scores was used as the baseline. The difference between this number and the post-stimulation scores were calculated for each participant. The mean and standard deviation for the change in scores from the median of the baseline scores is presented for each treatment group for scores reported immediately after TMS and 6 weeks post TMS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Occipital Transcranial Magnetic Stimulation | Mal de Debarquement Balance Rating Scale | Immediate change | -1.8 score on a scale | Standard Deviation 1.3 |
| Occipital Transcranial Magnetic Stimulation | Mal de Debarquement Balance Rating Scale | 6 week change | -1.1 score on a scale | Standard Deviation 1.7 |
| Vermis Transcranial Magnetic Stimulation | Mal de Debarquement Balance Rating Scale | Immediate change | -1.3 score on a scale | Standard Deviation 0.9 |
| Vermis Transcranial Magnetic Stimulation | Mal de Debarquement Balance Rating Scale | 6 week change | -1.3 score on a scale | Standard Deviation 1.6 |
| Cerebellar Hemisphere Control Transcranial Magnetic Stimulation | Mal de Debarquement Balance Rating Scale | Immediate change | -0.1 score on a scale | Standard Deviation 0.5 |
| Cerebellar Hemisphere Control Transcranial Magnetic Stimulation | Mal de Debarquement Balance Rating Scale | 6 week change | -0.1 score on a scale | Standard Deviation 0.5 |
Comparison: This was an N-of-1 pilot study in which all participants received one session of each of 3 targets and chose which of the 3 led to the most acute reduction in intensity of rocking. The participants were treated with the target that they chose and then completed post stimulation diaries.p-value: 0.0316ANOVA