Dyskinesias, Movement Disorders, Parkinson Disease
Conditions
Keywords
Dyskinesia, Levodopa, Movement Disorders, Parkinson Disease
Brief summary
The ultimate goal of this proposal is to reduce dyskinesia in Parkinson's Disease (PD) patients. Dyskinesias are abnormal movements, often caused by the standard treatment for PD symptoms, levodopa. In this study, we will test if biochemical devices are equal to the clinical rating system in measuring dyskinesias.
Detailed description
Levodopa induced dyskinesia (LID) is a major problem associated with chronic use of levodopa (LD) for symptomatic treatment of Parkinson's disease (PD). LD remains our most potent therapy and nearly all PD patients will use it. A substantial portion of them will experience LID, with the impact ranging from non-interfering to severely disabling. The objective of this study is to develop reliable and sensitive objective measures of LID that will quantify muscular control and postural stability in subjects with dyskinesia. While the gold standard of measuring LID is the subjective RS, we will determine if objective biochemical devices will equal the reliability and validity of CRS. We hypothesize that force plate technology quantifies postural sway movements best, and pinch-grip will best quantify muscle overflow force during voluntary movements. We will compare two biomechanical devices and a traditional clinical rating scale (CRS). Once biomechanical instrument measures LID in the setting of voluntary muscle activity, the other acquires LID data related to postural sway.. A cross-section of LD-treated patients with and without clinically apparent dyskinesia will be used to assess the measures. 32 subjects will be invited to participate, 24 with PD and 8 age-matched controls (likely unaffected spouses) without neurologic disease. Of the PD patients 7 will have no clinically apparent dyskinesia, 7 will have mild dyskinesia and 7 with moderate to severe dyskinesia will be recruited (3 additional subjects are included to account for missing data or drop-outs). They will comfortably stand with their feet placed in a preset marked stance on the force plate either with or without a mental task and pick up a pinch-grip device multiple times. Testing will be done in the effective motor on and off states to establish validity and reliability of instrument data, as these states often reflect the usual clinical experience of patients. The second method for rating dyskinesia will be the Clinical Rating Scale. Subjects will be rated while standing on the force plate during both mental task and non-mental task conditions. All subjects will undergo this testing. Healthy subjects will undergo this testing three times during one visit. Subjects with PD will be admitted overnight, and have seven testing periods which will vary in the number of times the procedures will be done. Inpatient subjects will also receive 1mg/kg/hr or 1.5mg/kg/hr of intravenous levodopa depending on their everyday usage of levodopa or levodopa equivalent medications for 2 hours (9AM - 11AM) with carbidopa 25 mg po at 8AM, 10AM and noon to prevent nausea.
Interventions
IV Levodopa is given from 09:00 to 11:00 am during the testing phase of the study. The IV Levodopa allows the researchers to watch one full on and off levodopa cycle while in the inpatient unit.
Sponsors
Oregon Health and Science University
US Department of Veterans Affairs
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Clinical diagnosis of probable idiopathic Parkinson's Disease or no neurologic disease (no disease for controls only) * At least 21 years of age * Mini Mental Status Exam Score\>=25
Exclusion criteria
* Evidence of psychosis (hallucinations or delusions) by history * Any unstable medical condition * Currently using dopamine blocking medication * Currently taking anticoagulants or MAO inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gaitmat Stance Measurements (AUC) | Every 1/2 hour during an 8 hour period. | Gaitmat stance measurements were measured every half hour throughout an 8 hour period. Area under the curve was computed using the trapezoidal method for root mean squared velocity in the anterior-posterior direction. Each subject's unique baseline was used by computing the mean of the test-retest period measured at 08:00 am. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PD - No LID Parkinson's disease without levodopa-induced dyskinesia | 6 |
| PD - Mild LID Parkinson's disease with mild to moderate levodopa-induced dyskinesia (mAIMS \<= 7) | 11 |
| PD - Mod LID Parkinson's disease with moderate to severe levodopa-induced dyskinesia (mAIMS \> 8) | 4 |
| Controls - No PD Controls with no Parkinson's disease | 6 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | PD - No LID | PD - Mild LID | PD - Mod LID | Controls - No PD | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 6.1 | 62.8 years STANDARD_DEVIATION 10.6 | 61.4 years STANDARD_DEVIATION 6.8 | 68.3 years STANDARD_DEVIATION 8.2 | 64.0 years STANDARD_DEVIATION 8.7 |
| Duration of Disease (years) | 4.7 years STANDARD_DEVIATION 3.1 | 10.2 years STANDARD_DEVIATION 5 | 10.5 years STANDARD_DEVIATION 4.8 | 0 years STANDARD_DEVIATION 0 | 9.5 years STANDARD_DEVIATION 5.9 |
| mAIMS at Screening | 0 units on a scale STANDARD_DEVIATION 0 | 1.6 units on a scale STANDARD_DEVIATION 2.4 | 11.8 units on a scale STANDARD_DEVIATION 3.5 | 0 units on a scale STANDARD_DEVIATION 0 | 3.1 units on a scale STANDARD_DEVIATION 5 |
| Region of Enrollment United States | 6 participants | 11 participants | 4 participants | 6 participants | 27 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 3 Participants | 5 Participants | 23 Participants |
| UPDRS (part III) | 21.3 units on a scale STANDARD_DEVIATION 7.9 | 23.5 units on a scale STANDARD_DEVIATION 12.7 | 12.0 units on a scale STANDARD_DEVIATION 8 | 0 units on a scale STANDARD_DEVIATION 0 | 15.3 units on a scale STANDARD_DEVIATION 13.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 11 | 0 / 4 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 11 | 0 / 4 | 0 / 6 |
Outcome results
Primary
Gaitmat Stance Measurements (AUC)
Gaitmat stance measurements were measured every half hour throughout an 8 hour period. Area under the curve was computed using the trapezoidal method for root mean squared velocity in the anterior-posterior direction. Each subject's unique baseline was used by computing the mean of the test-retest period measured at 08:00 am.
Time frame: Every 1/2 hour during an 8 hour period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD - No LID | Gaitmat Stance Measurements (AUC) | 4.48 Root Mean Square of Velocity*Minutes | Standard Deviation 2.1 |
| PD - Mild LID | Gaitmat Stance Measurements (AUC) | 10.8 Root Mean Square of Velocity*Minutes | Standard Deviation 12.1 |
| PD - Mod LID | Gaitmat Stance Measurements (AUC) | 20.9 Root Mean Square of Velocity*Minutes | Standard Deviation 26 |
| Controls - No PD | Gaitmat Stance Measurements (AUC) | 2.8 Root Mean Square of Velocity*Minutes | Standard Deviation 0.95 |