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Cerebellar Transcranial Direct Current Stimulation in Parkinson's Disease

Cerebellar Transcranial Direct Current Stimulation in Parkinson's Disease

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04046055
Enrollment
7
Registered
2019-08-06
Start date
2019-12-01
Completion date
2020-04-01
Last updated
2022-11-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Brain Stimulation, Cerebellum, Parkinson Disease

Keywords

transcranial direct current stimulation, walking, balance

Brief summary

Parkinson's disease (PD) is the second most common neurodegenerative disorder and affects approximately 1 million people in the United States with total annual costs approaching 11 billion dollars. The most common symptoms of PD are tremor, stiffness, slowness, and trouble with balance/walking, which lead to severe impairments in performing activities of daily living. Current medical and surgical treatments for PD are either only mildly effective, expensive, or associated with a variety of side-effects. Therefore, the development of practical and effective add-ons to current therapeutic treatment approaches would have many benefits. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can affect brain activity and can help make long-term brain changes to improve functions like walking and balance. While a few initial research studies and review articles involving tDCS have concluded that tDCS may improve PD walking and balance, many results are not meaningful in real life and several crucial issues still prevent tDCS from being a useful add-on intervention in PD. These include the selection of stimulation sites (brain regions stimulated) and tDCS electrode placement. Most studies have targeted the motor cortex (brain region that controls intentional movement), but there is evidence that the cerebellum - which helps control gait and balance, is connected to several other brain areas, and is easily stimulated with tDCS - may be a likely location to further optimize walking and balance in PD. There is also evidence that certain electrodes placements may be better than others. Thus, the purpose of this study is to determine the effects of cerebellar tDCS stimulation using two different placement strategies on walking and balance in PD. Additionally, although many tDCS devices are capable of a range of stimulation intensities (for example, 0 mA - 5 mA), the intensities currently used in most tDCS research are less than 2 mA, which is sufficient to produce measurable improvements; but, these improvements may be expanded at higher intensities. In the beginning, when the safety of tDCS was still being established for human subjects, careful and moderate stimulation approaches were warranted. However, recent work using stimulation at higher intensities (for example, up to 4 mA) have been performed in different people and were found to have no additional negative side-effects. Now that the safety of tDCS at higher intensities is better established, studies exploring the differences in performance between moderate (i.e., 2 mA) and higher (i.e., 4 mA) intensities are necessary to determine if increasing the intensity increases the effectiveness of the desired outcome. Prospective participants will include 10 people with mild-moderate PD that will be recruited to complete five randomly-ordered stimulation sessions, separated by at least 5 days each. Each session will involve one visit to the Integrative Neurophysiology Laboratory (INPL) and will last for approximately one hour. Data collection is expected to take 4-6 months. Each session will include walking and balance testing performed while wearing the tDCS device. Total tDCS stimulation time for each session will be 25 minutes.

Detailed description

Parkinson's disease (PD) is the second most common neurodegenerative disorder and affects approximately 1 million people in the United States with total annual costs approaching 11 billion dollars. The most common symptoms of PD are tremor, stiffness, slowness, and trouble with balance/walking, which lead to severe impairments in performing activities of daily living. Current medical and surgical treatments for PD are either only mildly effective, expensive, or associated with a variety of side-effects. Therefore, the development of practical and effective add-ons to current therapeutic treatment approaches would have many benefits. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can affect brain activity and can help make long-term brain changes to improve functions like walking and balance. While a few initial research studies and review articles involving tDCS have concluded that tDCS may improve PD walking and balance, many results are not meaningful in real life and several crucial issues still prevent tDCS from being a useful add-on intervention in PD. These include the selection of stimulation sites (brain regions stimulated) and tDCS electrode placement. Most studies have targeted the motor cortex (brain region that controls intentional movement), but there is evidence that the cerebellum - which helps control gait and balance, is connected to several other brain areas, and is easily stimulated with tDCS - may be a likely location to further optimize walking and balance in PD. There is also evidence that certain electrodes placements may be better than others. Thus, the purpose of this study is to determine the effects of cerebellar tDCS stimulation using two different placement strategies on walking and balance in PD. Additionally, although many tDCS devices are capable of a range of stimulation intensities (for example, 0 mA - 5 mA), the intensities currently used in most tDCS research are less than 2 mA, which is sufficient to produce measurable improvements; but, these improvements may be expanded at higher intensities. In the beginning, when the safety of tDCS was still being established for human subjects, careful and moderate stimulation approaches were warranted. However, recent work using stimulation at higher intensities (for example, up to 4 mA) have been performed in different people and were found to have no additional negative side-effects. Now that the safety of tDCS at higher intensities is better established, studies exploring the differences in performance between moderate (i.e., 2 mA) and higher (i.e., 4 mA) intensities are necessary to determine if increasing the intensity increases the effectiveness of the desired outcome. Prospective participants will include 10 people with mild-moderate PD that will be recruited to complete five randomly-ordered stimulation sessions (baseline/SHAM, unilateral tDCS montage at 2 mA, unilateral tDCS montage at 4 mA, bilateral tDCS montage at 2 mA, and bilateral montage at 4 mA), separated by at least 5 days. Each session will involve one visit to the Integrative Neurophysiology Laboratory (INPL) and will last for approximately one hour. Data collection is expected to take 4-6 months. Each session will include gait (30-meter walk test \[30mWT\], 6-minute walk test \[6MWT\], Timed Up and Go \[TUG\]) and balance testing (standing on a force platform with either a firm surface or a foam surface) performed in conjunction with one of the five randomly-ordered stimulation conditions (SHAM, unilateral 2 mA, unilateral 4 mA, bilateral 2 mA, and bilateral 4 mA). Total tDCS stimulation time for each session will be 25 minutes. Gait characteristics (i.e., gait speed, stride length, step length, toe-off angle, etc.) and distance walked during the 30mWT and 6MWT will also be determined with inertial sensors (OPAL motion sensors).

Interventions

Uses weak electrical current (2 mA intensity) to either increase or decrease brain excitability and improve functional or cognitive outcomes.

Uses weak electrical current (4 mA intensity) to either increase or decrease brain excitability and improve functional or cognitive outcomes.

DEVICESham transcranial direct current stimulation

Uses weak electrical current (2 mA intensity) at the beginning and the end of a given stimulation period to control for potential placebo-like effects or participant expectation bias.

Sponsors

Thorsten Rudroff
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE

Masking description

Participants will be blind to the different stimulation intensities (sham, 2 mA, 4 mA)

Intervention model description

All participants completed all 5 randomly ordered tDCS sessions (sham, unilateral 2 mA, unilateral4 mA, bilateral 2 mA, and bilateral 4 mA.

Eligibility

Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No

Inclusion criteria

* 1\) Adult (50-90 yrs) with a positive diagnosis of Parkinson's disease from a movement disorder specialist * 2\) an unchanged regimen of dopaminergic medication for at least the last 3 months * 3\) able to independently walk for 6 min * 4\) without other chronic psychiatric or medical conditions * 5\) not taking any psychoactive medications

Exclusion criteria

* 1\) pregnant * 2\) known holes or fissures in the skull * 3\) metallic objects or implanted devices in the skull (e.g., metal plate, deep brain stimulator) * 4\) current or previous injuries or surgeries that cause unusual gait * 5\) score less than 24 or 17 on the Montreal Cognitive Assessment or telephone-Montreal Cognitive Assessment, respectively * 6\) experience freezing of gait * 7\) a diagnosis of dementia or other neurodegenerative diseases

Design outcomes

Primary

MeasureTime frameDescription
Movement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute1 minuteStand as still as possible on a foam surface for 1 minute with the eyes open. Calculate the area of an ellipse that contains 95% of the 2D trace of the center of pressure movement.
Speed Walked During 30 Meter Walk Test10 minutesWalk as fast and as safe as possible over 30 meter
Time to Complete the Timed Up and Go Test10 minutesFrom a seated position, stand up, walk 5 meters, turn around, walk back, and sit back down in the chair.
Movement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Firm Surface (Force Platform) for 1 Minute1 minuteStand as still as possible on a firm surface for 1 minute with the eyes open. Calculate the area of an ellipse that contains 95% of the 2D trace of the center of pressure movement.

Secondary

MeasureTime frameDescription
Movement of the Center of Pressure (1D; Forward-backward) While Standing on a Firm Surface (Force Platform) for 1 Minute1 minuteStand as still as possible on a firm surface for 1 minute with the eyes open.
Movement of the Center of Pressure (1D; Left-Right) While Standing on a Firm Surface (Force Platform) for 1 Minute1 minuteStand as still as possible on a firm surface for 1 minute with the eyes open.
Movement of the Center of Pressure (1D; Forward-backward) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute1 minuteStand as still as possible on a foam surface for 1 minute with the eyes open.
Movement of the Center of Pressure (1D; Left-Right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute1 minuteStand as still as possible on a foam surface for 1 minute with the eyes open.

Countries

United States

Participant flow

Pre-assignment details

All subjects in this study completed all of the study arms (repeated-measure design).

Participants by arm

ArmCount
Sham, Unilateral 2 mA, Bilateral 2 mA, Unilateral 4 mA, and Bilateral 4 mA)
Sham transcranial direct current stimulation: Uses weak electrical current (2 mA intensity) at the beginning and the end of a given stimulation period to control for potential placebo-like effects or participant expectation bias. A unilateral cerebellar montage with the anode three cm lateral to the inion on the side ipsilateral to the more PD-affected side and the cathode on the ipsilateral cheek. Stimulation is ramped up to 2 mA over the first 30 seconds and stays at 2 mA for the remainder of the stimulation time. Transcranial direct current stimulation at 2 mA/4mA: Uses weak electrical current to either increase or decrease brain excitability and improve functional or cognitive outcomes. Bilateral cerebellar tDCS will have both electrodes placed 3 cm to either side of the inion, with the anode assigned to the most PD-affected side and the cathode assigned to the less PD-affected side. Stimulation is ramped up to 2 mA over the first 30 seconds and stays at 2 mA/4mA for the remainder of the stimulation time.
7
Total7

Baseline characteristics

CharacteristicSham, Unilateral 2 mA, Bilateral 2 mA, Unilateral 4 mA, and Bilateral 4 mA)
Age, Continuous72.4 years
STANDARD_DEVIATION 6.4
Race and Ethnicity Not Collected— Participants
Region of Enrollment
United States
7 Participants
Sex: Female, Male
Female
2 Participants
Sex: Female, Male
Male
5 Participants
UPDRS-III32.6 Scores on scale
STANDARD_DEVIATION 14.2

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
deaths
Total, all-cause mortality
0 / 70 / 70 / 70 / 70 / 7
other
Total, other adverse events
0 / 70 / 70 / 70 / 70 / 7
serious
Total, serious adverse events
0 / 70 / 70 / 70 / 70 / 7

Outcome results

Primary

Movement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Firm Surface (Force Platform) for 1 Minute

Stand as still as possible on a firm surface for 1 minute with the eyes open. Calculate the area of an ellipse that contains 95% of the 2D trace of the center of pressure movement.

Time frame: 1 minute

ArmMeasureValue (MEAN)Dispersion
Sham 4 mAMovement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Firm Surface (Force Platform) for 1 Minute3.22 centimeters squared (cm^2)Standard Deviation 2.56
Unilateral 2 mAMovement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Firm Surface (Force Platform) for 1 Minute2.47 centimeters squared (cm^2)Standard Deviation 2.34
Bilateral 2 mAMovement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Firm Surface (Force Platform) for 1 Minute1.72 centimeters squared (cm^2)Standard Deviation 0.5
Unilateral 4 mAMovement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Firm Surface (Force Platform) for 1 Minute1.60 centimeters squared (cm^2)Standard Deviation 0.74
Bilateral 4 mAMovement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Firm Surface (Force Platform) for 1 Minute1.57 centimeters squared (cm^2)Standard Deviation 0.39
Primary

Movement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute

Stand as still as possible on a foam surface for 1 minute with the eyes open. Calculate the area of an ellipse that contains 95% of the 2D trace of the center of pressure movement.

Time frame: 1 minute

ArmMeasureValue (MEAN)Dispersion
Sham 4 mAMovement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute8.34 centimeters squared (cm^2)Standard Deviation 7.57
Unilateral 2 mAMovement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute7.53 centimeters squared (cm^2)Standard Deviation 4.35
Bilateral 2 mAMovement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute9.36 centimeters squared (cm^2)Standard Deviation 6.9
Unilateral 4 mAMovement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute8.30 centimeters squared (cm^2)Standard Deviation 6.4
Bilateral 4 mAMovement of the Center of Pressure (2D; Forward-backward, Left-right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute7.60 centimeters squared (cm^2)Standard Deviation 3.63
Primary

Speed Walked During 30 Meter Walk Test

Walk as fast and as safe as possible over 30 meter

Time frame: 10 minutes

ArmMeasureValue (MEAN)Dispersion
Sham 4 mASpeed Walked During 30 Meter Walk Test5.63 meters per second (m/s)Standard Deviation 0.84
Unilateral 2 mASpeed Walked During 30 Meter Walk Test5.65 meters per second (m/s)Standard Deviation 1.04
Bilateral 2 mASpeed Walked During 30 Meter Walk Test5.77 meters per second (m/s)Standard Deviation 1.07
Unilateral 4 mASpeed Walked During 30 Meter Walk Test5.86 meters per second (m/s)Standard Deviation 1.06
Bilateral 4 mASpeed Walked During 30 Meter Walk Test5.77 meters per second (m/s)Standard Deviation 1.24
Primary

Time to Complete the Timed Up and Go Test

From a seated position, stand up, walk 5 meters, turn around, walk back, and sit back down in the chair.

Time frame: 10 minutes

ArmMeasureValue (MEAN)Dispersion
Sham 4 mATime to Complete the Timed Up and Go Test11.9 seconds (s)Standard Deviation 2.7
Unilateral 2 mATime to Complete the Timed Up and Go Test12.43 seconds (s)Standard Deviation 2.32
Bilateral 2 mATime to Complete the Timed Up and Go Test12.80 seconds (s)Standard Deviation 2.42
Unilateral 4 mATime to Complete the Timed Up and Go Test12.42 seconds (s)Standard Deviation 2.72
Bilateral 4 mATime to Complete the Timed Up and Go Test12.70 seconds (s)Standard Deviation 3.28
Secondary

Movement of the Center of Pressure (1D; Forward-backward) While Standing on a Firm Surface (Force Platform) for 1 Minute

Stand as still as possible on a firm surface for 1 minute with the eyes open.

Time frame: 1 minute

ArmMeasureValue (MEAN)Dispersion
Sham 4 mAMovement of the Center of Pressure (1D; Forward-backward) While Standing on a Firm Surface (Force Platform) for 1 Minute2.38 centimeters (cm)Standard Deviation 0.7
Unilateral 2 mAMovement of the Center of Pressure (1D; Forward-backward) While Standing on a Firm Surface (Force Platform) for 1 Minute2.90 centimeters (cm)Standard Deviation 0.91
Bilateral 2 mAMovement of the Center of Pressure (1D; Forward-backward) While Standing on a Firm Surface (Force Platform) for 1 Minute2.25 centimeters (cm)Standard Deviation 0.62
Unilateral 4 mAMovement of the Center of Pressure (1D; Forward-backward) While Standing on a Firm Surface (Force Platform) for 1 Minute2.25 centimeters (cm)Standard Deviation 0.69
Bilateral 4 mAMovement of the Center of Pressure (1D; Forward-backward) While Standing on a Firm Surface (Force Platform) for 1 Minute2.86 centimeters (cm)Standard Deviation 1.02
Secondary

Movement of the Center of Pressure (1D; Forward-backward) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute

Stand as still as possible on a foam surface for 1 minute with the eyes open.

Time frame: 1 minute

ArmMeasureValue (MEAN)Dispersion
Sham 4 mAMovement of the Center of Pressure (1D; Forward-backward) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute4.4 centimeters (cm)Standard Deviation 2.8
Unilateral 2 mAMovement of the Center of Pressure (1D; Forward-backward) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute4.0 centimeters (cm)Standard Deviation 1.1
Bilateral 2 mAMovement of the Center of Pressure (1D; Forward-backward) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute4.5 centimeters (cm)Standard Deviation 1.8
Unilateral 4 mAMovement of the Center of Pressure (1D; Forward-backward) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute4.11 centimeters (cm)Standard Deviation 1.41
Bilateral 4 mAMovement of the Center of Pressure (1D; Forward-backward) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute4.08 centimeters (cm)Standard Deviation 1.19
Secondary

Movement of the Center of Pressure (1D; Left-Right) While Standing on a Firm Surface (Force Platform) for 1 Minute

Stand as still as possible on a firm surface for 1 minute with the eyes open.

Time frame: 1 minute

ArmMeasureValue (MEAN)Dispersion
Sham 4 mAMovement of the Center of Pressure (1D; Left-Right) While Standing on a Firm Surface (Force Platform) for 1 Minute2.1 centimeters (cm)Standard Deviation 1.8
Unilateral 2 mAMovement of the Center of Pressure (1D; Left-Right) While Standing on a Firm Surface (Force Platform) for 1 Minute1.4 centimeters (cm)Standard Deviation 0.6
Bilateral 2 mAMovement of the Center of Pressure (1D; Left-Right) While Standing on a Firm Surface (Force Platform) for 1 Minute1.3 centimeters (cm)Standard Deviation 0.3
Unilateral 4 mAMovement of the Center of Pressure (1D; Left-Right) While Standing on a Firm Surface (Force Platform) for 1 Minute1.1 centimeters (cm)Standard Deviation 0.4
Bilateral 4 mAMovement of the Center of Pressure (1D; Left-Right) While Standing on a Firm Surface (Force Platform) for 1 Minute1.1 centimeters (cm)Standard Deviation 0.4
Secondary

Movement of the Center of Pressure (1D; Left-Right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute

Stand as still as possible on a foam surface for 1 minute with the eyes open.

Time frame: 1 minute

ArmMeasureValue (MEAN)Dispersion
Sham 4 mAMovement of the Center of Pressure (1D; Left-Right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute3.6 centimeters (cm)Standard Deviation 1.8
Unilateral 2 mAMovement of the Center of Pressure (1D; Left-Right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute3.4 centimeters (cm)Standard Deviation 1
Bilateral 2 mAMovement of the Center of Pressure (1D; Left-Right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute3.3 centimeters (cm)Standard Deviation 1.3
Unilateral 4 mAMovement of the Center of Pressure (1D; Left-Right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute3.3 centimeters (cm)Standard Deviation 1.2
Bilateral 4 mAMovement of the Center of Pressure (1D; Left-Right) While Standing on a Foam Surface (6 cm Foam Pad Placed on Top of Force Platform) for 1 Minute3.3 centimeters (cm)Standard Deviation 1

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026