Parkinson Disease
Conditions
Keywords
Human Brain, Electrical Stimulation, Parkinson Disease, PD
Brief summary
This study will examine the effects of transcranial direct current stimulation (tDCS) on gait (walking) problems and rigidity in patients with Parkinson's disease. tDCS is a method of brain stimulation that may be able to change the electrical activity of the nerves of the brain, possibly causing Parkinson's disease symptoms to improve. Patients between 40 and 80 years of age with moderately severe Parkinson's disease whose main symptoms are problems with walking, including freezing, or rigidity, may be eligible for this study. Candidates must be taking Sinemet or another L-DOPA drug and not have too much tremor. Participants will be assigned to receive either real or sham (placebo) tDCS. Both groups will have eight treatments over 3-1/2 weeks. For the tDCS, electrodes are placed on wet pads on the scalp. An electrical current passes through the electrodes, travels through the scalp and skull, and causes small electrical currents in the cortex-the outer part of the brain. Participants will have a neurological examination, including an evaluation of walking, just before and just after each tDCS session. Patients' motor function will be re-evaluated at 1, 3, and 6 months after the last tDCS treatment. ...
Detailed description
The treatment of Parkinson's disease (PD) needs further improvement, particularly in the areas of gait and freezing. Transcranial direct current stimulation (tDCS) which passes weak direct current (DC) current through the skull and across the cortex has been done for many years with numerous effects described in healthy subjects and patients with mental illness. Recently, it has been shown by objective means, in controlled experiments, that this type of treatment has robust and lasting effects on the excitability of the motor cortex in healthy humans. We hypothesize that tDCS will have a beneficial effect on gait and freezing in medicated patients, and we propose to test this in a controlled trial. Specifically, we propose to look at the effect of 1-2 mA tDCS with anode position over the frontal poles and/or premotor and primary motor cortex, and cathode over mastoid process. Over a one-year period, we will enroll 42 adults with PD and evaluate the acute tDCS effects over a period of four weeks (eight tDCS sessions, nine visits). Additional ratings will be done at one and three months after the end of tDCS sessions. Symptoms will be evaluated with standard tests of motor function, including the Unified Parkinson's Disease Rating Scale (UPDRS) and specific tests of gait and freezing. We will also look for cumulative, long-lasting effects over the three-month period.
Interventions
DEVICEPhoressor II (IOMED)
sham stimulation
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: Patients with PD corresponding to inclusion criteria will be recruited from the Human Motor Control Section Clinic (HMCS). Subjects will be men and women aged 40-80 years with DOPA-responsive, akinetic-rigid PD. Patients who have never participated in HMCS protocols for PD will be interviewed and examined by either the principal investigator or a physician from the Brain Stimulation Unit or HMCS in order to establish the diagnosis of PD and rule out any neurological condition. Only patients with a Hoehm and Yahr grade of 2 to 4 while off will be accepted. Patients must be on a regimen including levodopa. The total dose of levodopa and dopamine agonists (using dopamine equivalents) has to be equal to or more than 375 milligrams per day. Other anti-parkinsonian medications are also acceptable. Patients should have problems with walking, including freezing, so that their gait time for a 10-meter distance will be six seconds or more.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gait Speed Before and After Real and Sham tDCS. | baseline, 1 day post, 1 month post, 3 months post-tDCS | Gait speed was measured by the time it took the subject to walk 10m. Subjects were instructed to walk at a fast pace without taking the risk of falling, wearing the same shoes and using assistive devices consistently if needed. Gait speed was measured at baseline and post-tDCS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | baseline, 1 day post, 1 month post, 3 months post-tDCS | The Total Unified Parkinson's Disease Rating Scale (UPDRS) is an overall clinical rating scale that quantifies the signs and symptoms of Parkinson's disease. The total UPDRS score was obtained from subject examination, subject interviews and questionnaires. The UPDRS encompasses measurement of mentation, behavior, mood, activities of daily living and motor skills. The total UPDRS scores ranges from 0 (not affected) to 176 (most severely affected). The UPDRS was administred at baseline and at 1 day post, 1 month post, and 3 months post tDCS or sham, while on medication and off medication. |
| UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | baseline, 1 day post, 1 month post, and 3 months post real and sham tDCS | The Motor Unified Parkinson's Disease Rating Scale (UPDRS) includes only the motor assessment of the UPDRS (Part III) and examines speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability and body bradykinesia. The scores range from 0 (no motor impairment) to 108 (severe motor impairment). The Motor UPDRS was administred at baseline and at 1 day post, 1 month post, and 3 months post tDCS or sham. Subjects were assessed on medication and off medication. |
| Bradykinesia Measure Before and After Real and Sham tDCS. | baseline, 1 day post, 1 month post, 3 months post tDCS | Bradykinesia refers to the slowness in executing a movement. Bradykinesia was assessed by measuring the time in seconds it takes to do the following sequence, 10 times: 1) hand closing and opening while squeezing a ball 2) elbow flexion 3) hand closing and opening, and 4) elbow extension. Subjects were allowed to practice these hand and arm movements until performance appeared not to get faster, and then were abstained from further practice to minimize learning effects. The time it takes subjects to execute the entire sequence 10 times with either the left or right arm/hand was measured. Means are reported for each group. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Real tDCS Subjects received real transcranial direct current stimulation | 13 |
| Sham tDCS Subjects received sham transcranial direct current stimulation | 12 |
| Total | 25 |
Baseline characteristics
| Characteristic | Real tDCS | Sham tDCS | Total |
|---|---|---|---|
| Age Continuous | 63.6 years STANDARD_DEVIATION 9 | 64.2 years STANDARD_DEVIATION 8.8 | 63.9 years STANDARD_DEVIATION 8.5 |
| Hoehn-Yahr off medication | 2.7 units on scale STANDARD_DEVIATION 0.3 | 2.9 units on scale STANDARD_DEVIATION 0.4 | 2.8 units on scale STANDARD_DEVIATION 0.4 |
| Hoehn-Yahr on medication | 2.5 units on a scale STANDARD_DEVIATION 0.1 | 2.4 units on a scale STANDARD_DEVIATION 0.2 | 2.42 units on a scale STANDARD_DEVIATION 0.2 |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 13 | 0 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 |
Outcome results
Primary
Gait Speed Before and After Real and Sham tDCS.
Gait speed was measured by the time it took the subject to walk 10m. Subjects were instructed to walk at a fast pace without taking the risk of falling, wearing the same shoes and using assistive devices consistently if needed. Gait speed was measured at baseline and post-tDCS.
Time frame: baseline, 1 day post, 1 month post, 3 months post-tDCS
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS While on Medication | Gait Speed Before and After Real and Sham tDCS. | Baseline | 8.7 Seconds | Standard Deviation 2.4 |
| Real tDCS While on Medication | Gait Speed Before and After Real and Sham tDCS. | One day post tDCS | 7.2 Seconds | Standard Deviation 1.6 |
| Real tDCS While on Medication | Gait Speed Before and After Real and Sham tDCS. | Three month post tDCS | 7.2 Seconds | Standard Deviation 1.5 |
| Real tDCS While on Medication | Gait Speed Before and After Real and Sham tDCS. | One month post tDCS | 7.0 Seconds | Standard Deviation 1.2 |
| Sham tDCS While on Medication | Gait Speed Before and After Real and Sham tDCS. | One day post tDCS | 7.6 Seconds | Standard Deviation 1.5 |
| Sham tDCS While on Medication | Gait Speed Before and After Real and Sham tDCS. | Three month post tDCS | 8.8 Seconds | Standard Deviation 4.2 |
| Sham tDCS While on Medication | Gait Speed Before and After Real and Sham tDCS. | One month post tDCS | 8.7 Seconds | Standard Deviation 3.7 |
| Sham tDCS While on Medication | Gait Speed Before and After Real and Sham tDCS. | Baseline | 8.6 Seconds | Standard Deviation 2.6 |
| Real tDCS While Off Medication | Gait Speed Before and After Real and Sham tDCS. | Baseline | 9.7 Seconds | Standard Deviation 3.6 |
| Real tDCS While Off Medication | Gait Speed Before and After Real and Sham tDCS. | Three month post tDCS | 9.0 Seconds | Standard Deviation 4.8 |
| Real tDCS While Off Medication | Gait Speed Before and After Real and Sham tDCS. | One month post tDCS | 7.6 Seconds | Standard Deviation 1.4 |
| Real tDCS While Off Medication | Gait Speed Before and After Real and Sham tDCS. | One day post tDCS | 7.5 Seconds | Standard Deviation 1.5 |
| Sham tDCS While Off Medication | Gait Speed Before and After Real and Sham tDCS. | Three month post tDCS | 9.7 Seconds | Standard Deviation 4.6 |
| Sham tDCS While Off Medication | Gait Speed Before and After Real and Sham tDCS. | Baseline | 9.5 Seconds | Standard Deviation 4.1 |
| Sham tDCS While Off Medication | Gait Speed Before and After Real and Sham tDCS. | One day post tDCS | 9.8 Seconds | Standard Deviation 4.7 |
| Sham tDCS While Off Medication | Gait Speed Before and After Real and Sham tDCS. | One month post tDCS | 10.9 Seconds | Standard Deviation 7.3 |
Secondary
Bradykinesia Measure Before and After Real and Sham tDCS.
Bradykinesia refers to the slowness in executing a movement. Bradykinesia was assessed by measuring the time in seconds it takes to do the following sequence, 10 times: 1) hand closing and opening while squeezing a ball 2) elbow flexion 3) hand closing and opening, and 4) elbow extension. Subjects were allowed to practice these hand and arm movements until performance appeared not to get faster, and then were abstained from further practice to minimize learning effects. The time it takes subjects to execute the entire sequence 10 times with either the left or right arm/hand was measured. Means are reported for each group.
Time frame: baseline, 1 day post, 1 month post, 3 months post tDCS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS While on Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | Baseline | 12.3 seconds | Standard Deviation 3.5 |
| Real tDCS While on Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 1 day post tDCS | 8.5 seconds | Standard Deviation 1.8 |
| Real tDCS While on Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 1 month post tDCS | 9.1 seconds | Standard Deviation 2 |
| Real tDCS While on Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 3 months post tDCS | 9.0 seconds | Standard Deviation 1.8 |
| Sham tDCS While on Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 1 day post tDCS | 10.5 seconds | Standard Deviation 2.3 |
| Sham tDCS While on Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 1 month post tDCS | 10.5 seconds | Standard Deviation 2.3 |
| Sham tDCS While on Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 3 months post tDCS | 10.4 seconds | Standard Deviation 2.5 |
| Sham tDCS While on Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | Baseline | 12.3 seconds | Standard Deviation 4 |
| Real tDCS While Off Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 1 month post tDCS | 9.4 seconds | Standard Deviation 1.9 |
| Real tDCS While Off Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 1 day post tDCS | 8.9 seconds | Standard Deviation 1.8 |
| Real tDCS While Off Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 3 months post tDCS | 9.7 seconds | Standard Deviation 2 |
| Real tDCS While Off Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | Baseline | 14.5 seconds | Standard Deviation 4.5 |
| Sham tDCS While Off Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 3 months post tDCS | 11.6 seconds | Standard Deviation 4 |
| Sham tDCS While Off Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 1 day post tDCS | 11.1 seconds | Standard Deviation 2.6 |
| Sham tDCS While Off Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | Baseline | 14.4 seconds | Standard Deviation 5.3 |
| Sham tDCS While Off Medication | Bradykinesia Measure Before and After Real and Sham tDCS. | 1 month post tDCS | 11.7 seconds | Standard Deviation 3.8 |
Secondary
UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course.
The Motor Unified Parkinson's Disease Rating Scale (UPDRS) includes only the motor assessment of the UPDRS (Part III) and examines speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability and body bradykinesia. The scores range from 0 (no motor impairment) to 108 (severe motor impairment). The Motor UPDRS was administred at baseline and at 1 day post, 1 month post, and 3 months post tDCS or sham. Subjects were assessed on medication and off medication.
Time frame: baseline, 1 day post, 1 month post, and 3 months post real and sham tDCS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS While on Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | Baseline | 22.2 units on a scale | Standard Deviation 8.7 |
| Real tDCS While on Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 day post tDCS | 20.4 units on a scale | Standard Deviation 7.7 |
| Real tDCS While on Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 month post tDCS | 22.7 units on a scale | Standard Deviation 6.6 |
| Real tDCS While on Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 3 months post tDCS | 23.1 units on a scale | Standard Deviation 7.8 |
| Sham tDCS While on Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 day post tDCS | 15.6 units on a scale | Standard Deviation 7.9 |
| Sham tDCS While on Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 month post tDCS | 18.6 units on a scale | Standard Deviation 8.1 |
| Sham tDCS While on Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 3 months post tDCS | 17.6 units on a scale | Standard Deviation 8.5 |
| Sham tDCS While on Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | Baseline | 17.5 units on a scale | Standard Deviation 8 |
| Real tDCS While Off Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 month post tDCS | 31.4 units on a scale | Standard Deviation 9.9 |
| Real tDCS While Off Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 day post tDCS | 31.5 units on a scale | Standard Deviation 7.3 |
| Real tDCS While Off Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 3 months post tDCS | 34.0 units on a scale | Standard Deviation 10.3 |
| Real tDCS While Off Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | Baseline | 34.0 units on a scale | Standard Deviation 10 |
| Sham tDCS While Off Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 3 months post tDCS | 27.1 units on a scale | Standard Deviation 10.5 |
| Sham tDCS While Off Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 day post tDCS | 29.0 units on a scale | Standard Deviation 11.7 |
| Sham tDCS While Off Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | Baseline | 26.5 units on a scale | Standard Deviation 8.4 |
| Sham tDCS While Off Medication | UPDRS Motor Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 month post tDCS | 29.0 units on a scale | Standard Deviation 8.1 |
Secondary
UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course.
The Total Unified Parkinson's Disease Rating Scale (UPDRS) is an overall clinical rating scale that quantifies the signs and symptoms of Parkinson's disease. The total UPDRS score was obtained from subject examination, subject interviews and questionnaires. The UPDRS encompasses measurement of mentation, behavior, mood, activities of daily living and motor skills. The total UPDRS scores ranges from 0 (not affected) to 176 (most severely affected). The UPDRS was administred at baseline and at 1 day post, 1 month post, and 3 months post tDCS or sham, while on medication and off medication.
Time frame: baseline, 1 day post, 1 month post, 3 months post-tDCS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS While on Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | Baseline | 42.5 units on a scale | Standard Deviation 10.8 |
| Real tDCS While on Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 day post tDCS | 36.9 units on a scale | Standard Deviation 11.1 |
| Real tDCS While on Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 month post tDCS | 42.5 units on a scale | Standard Deviation 7.8 |
| Real tDCS While on Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 3 months post tDCS | 43.4 units on a scale | Standard Deviation 9.1 |
| Sham tDCS While on Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 day post tDCS | 32.0 units on a scale | Standard Deviation 11.7 |
| Sham tDCS While on Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 month post tDCS | 36.1 units on a scale | Standard Deviation 11 |
| Sham tDCS While on Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 3 months post tDCS | 35.5 units on a scale | Standard Deviation 13.8 |
| Sham tDCS While on Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | Baseline | 39.5 units on a scale | Standard Deviation 12.8 |
| Real tDCS While Off Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 month post tDCS | 56.1 units on a scale | Standard Deviation 13.2 |
| Real tDCS While Off Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 day post tDCS | 54.1 units on a scale | Standard Deviation 13.1 |
| Real tDCS While Off Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 3 months post tDCS | 60.1 units on a scale | Standard Deviation 13.6 |
| Real tDCS While Off Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | Baseline | 58.4 units on a scale | Standard Deviation 14.7 |
| Sham tDCS While Off Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 3 months post tDCS | 52.4 units on a scale | Standard Deviation 17 |
| Sham tDCS While Off Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 day post tDCS | 50.4 units on a scale | Standard Deviation 16.2 |
| Sham tDCS While Off Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | Baseline | 53.6 units on a scale | Standard Deviation 14.5 |
| Sham tDCS While Off Medication | UPDRS Total Scores Before and After Real tDCS Course and After Sham tDCS Course. | 1 month post tDCS | 54.4 units on a scale | Standard Deviation 12.1 |