Trial Outcomes & Findings for Vigor and the LDR in Parkinson Disease (NCT NCT04821830)

NCT ID: NCT04821830

Last Updated: 2025-07-18

Results Overview

Measurement of bradykinesia. With the hand most affected by PD, participants were instructed to alternately tap 2 manual counters spaced 20 cm apart as rapidly as possible for 1 minute. The longer participants took to complete the task indicated a higher degree of bradykinesia affecting them. This task was administered over the course of 4 visits during the following conditions: Visit 1. Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2. After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3. 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4. After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

19 participants

Primary outcome timeframe

Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

Results posted on

2025-07-18

Participant Flow

Participant milestones

Participant milestones
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
Participants will undergo evaluation of the relationship between the Long Duration Response (LDR) and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Experiment 2: Primary Outcome (Value Driven Attentional Oculomotor Capture)
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and the outcome measure: Grip Strength Task - Measurement of Incentive-Outcome Coupling - Movement Vigor. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants from Experiment 2 were not included in Experiment 1.
Overall Study
STARTED
12
7
Overall Study
COMPLETED
11
7
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
Participants will undergo evaluation of the relationship between the Long Duration Response (LDR) and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Experiment 2: Primary Outcome (Value Driven Attentional Oculomotor Capture)
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and the outcome measure: Grip Strength Task - Measurement of Incentive-Outcome Coupling - Movement Vigor. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants from Experiment 2 were not included in Experiment 1.
Overall Study
Withdrawal by Subject
1
0

Baseline Characteristics

Vigor and the LDR in Parkinson Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=12 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Experiment 2: Primary Outcome (Value Driven Attentional Oculomotor Capture)
n=7 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and the outcome measure: Grip Strength Task - Measurement of Incentive-Outcome Coupling - Movement Vigor. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants from Experiment 2 were not included in Experiment 1.
Total
n=19 Participants
Total of all reporting groups
Age, Continuous
67.0 years
STANDARD_DEVIATION 6.1 • n=5 Participants
69.7 years
STANDARD_DEVIATION 8.01 • n=7 Participants
68.0 years
STANDARD_DEVIATION 6.78 • n=5 Participants
Sex: Female, Male
Female
5 Participants
n=5 Participants
4 Participants
n=7 Participants
9 Participants
n=5 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants
3 Participants
n=7 Participants
10 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
12 Participants
n=5 Participants
7 Participants
n=7 Participants
19 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
White
12 Participants
n=5 Participants
7 Participants
n=7 Participants
19 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
12 Participants
n=5 Participants
7 Participants
n=7 Participants
19 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

Measurement of bradykinesia. With the hand most affected by PD, participants were instructed to alternately tap 2 manual counters spaced 20 cm apart as rapidly as possible for 1 minute. The longer participants took to complete the task indicated a higher degree of bradykinesia affecting them. This task was administered over the course of 4 visits during the following conditions: Visit 1. Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2. After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3. 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4. After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa).

Outcome measures

Outcome measures
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=11 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Tapping Speed Task - Experiment 1
Visit 1 - Baseline: Treatment Naïve Subject
110.52 taps/min
Standard Deviation 23.12
Tapping Speed Task - Experiment 1
Visit 3 - LDR: Chronically Treated - "Practical Off" State
138.43 taps/min
Standard Deviation 42.49
Tapping Speed Task - Experiment 1
Visit 4 - SDR + LDR: Chronically Treated - After Usual L-Dopa
145.86 taps/min
Standard Deviation 41.94
Tapping Speed Task - Experiment 1
Visit 2 - SDR: Treatment Naïve Subject After Acute L-Dopa
128.89 taps/min
Standard Deviation 39.31

PRIMARY outcome

Timeframe: Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

Population: Interim analysis disclosed after 6 participants that outcome would be very unlikely to produce significant findings, so administration of this outcome was performed only for 6 participants before it was stopped.

Participants did a saccadic eye movement task involving rapid-eye movements from one point to another to assess the functionality of eye muscles and the brain's ability to control these movements. Participants had an initial training session and then had to complete the task with no distractors, low distractors, and high distractors. This task was administered over the course of 4 visits during the following conditions: Visit 1. Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2. After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3. 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4. After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa).

Outcome measures

Outcome measures
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=6 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - No Distractor Value
SDR: Treatment Naïve Subject After Acute L-Dopa
1.057 seconds
Standard Deviation 0.06
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - No Distractor Value
LDR: Chronically Treated - "Practical Off" State
1.03 seconds
Standard Deviation 0.06
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - No Distractor Value
SDR + LDR: Chronically Treated - After Usual L-Dopa
1.04 seconds
Standard Deviation 0.02
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - No Distractor Value
Baseline: Treatment Naïve Subject
1.14 seconds
Standard Deviation 0.09

PRIMARY outcome

Timeframe: Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

Population: Interim analysis disclosed after 6 participants that outcome would be very unlikely to produce significant findings, so administration of this outcome was performed only for 6 participants before it was stopped. Data for the training session was collected for participants during the high-distractor task. During the training session, 1 participant's data was not collected because of a computer issue.

Participants did a saccadic eye movement task involving rapid-eye movements from one point to another to assess the functionality of eye muscles and the brain's ability to control these movements. Participants had an initial training session and then had to complete the task with no distractors, low distractors, and high distractors. This task was administered over the course of 4 visits during the following conditions: Visit 1. Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2. After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3. 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4. After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa).

Outcome measures

Outcome measures
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=6 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - Low Distractor Value
Visit 1 - Training Session
0.97 seconds
Standard Deviation 0.02
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - Low Distractor Value
Visit 1 - Baseline: Treatment Naïve Subject
1.15 seconds
Standard Deviation 0.07
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - Low Distractor Value
Visit 2 - SDR: Treatment Naïve Subject After Acute L-Dopa
1.06 seconds
Standard Deviation 0.04
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - Low Distractor Value
Visit 3 - LDR: Chronically Treated - "Practical Off" State
1.03 seconds
Standard Deviation 0.05
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - Low Distractor Value
Visit 4 - SDR + LDR: Chronically Treated - After Usual L-Dopa
1.04 seconds
Standard Deviation 0.05

PRIMARY outcome

Timeframe: Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

Population: Interim analysis disclosed after 6 participants that outcome would be very unlikely to produce significant findings, so administration of this outcome was performed only for 6 participants before it was stopped. Data for the training session was collected for participants during the high-distractor task. During the training session, 1 participant's data was not collected because of a computer issue.

Participants did a saccadic eye movement task involving rapid-eye movements from one point to another to assess the functionality of eye muscles and the brain's ability to control these movements. Participants had an initial training session and then had to complete the task with no distractors, low distractors, and high distractors. This task was administered over the course of 4 visits during the following conditions: Visit 1. Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2. After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3. 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4. After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa).

Outcome measures

Outcome measures
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=6 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - High Distractor Value
Visit 1 - Training Session
0.97 seconds
Standard Deviation 0.02
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - High Distractor Value
Visit 1 - Baseline - Treatment Naïve Subject (Day 0)
1.12 seconds
Standard Deviation 0.04
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - High Distractor Value
Visit 3 - LDR: Chronically Treated - "Practical Off" State
1.03 seconds
Standard Deviation 0.06
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - High Distractor Value
Visit 4 - SDR + LDR: Chronically Treated - After Usual L-Dopa
1.04 seconds
Standard Deviation 0.04
Value Driven Attentional Oculomotor Capture Task - Experiment 2 - High Distractor Value
Visit 2 - SDR: Treatment Naïve Subject After Acute L-Dopa
1.05 seconds
Standard Deviation 0.05

PRIMARY outcome

Timeframe: Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

All participants were tasked with pushing a joystick with the hand most affected by PD symptoms in response to monetary incentives. Participants were presented with incentives of low ($5), medium ($10), and high value ($20) on each treatment day, and their movement time in pushing the joystick was measured over the course of 4 visits during the following conditions: Visit 1: Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2: After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3: 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4: After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa). Results reflect participants' response to the low incentive.

Outcome measures

Outcome measures
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=11 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Joystick Movement Task - Experiment 1 - Low Incentive
Baseline - Treatment Naïve Subject
0.24 seconds
Standard Deviation 0.12
Joystick Movement Task - Experiment 1 - Low Incentive
LDR: Chronically Treated - "Practical Off" State
0.20 seconds
Standard Deviation 0.10
Joystick Movement Task - Experiment 1 - Low Incentive
SDR + LDR: Chronically Treated - After Usual L-Dopa
0.19 seconds
Standard Deviation 0.10
Joystick Movement Task - Experiment 1 - Low Incentive
SDR: Treatment Naïve Subject After Acute L-Dopa
0.20 seconds
Standard Deviation 0.09

PRIMARY outcome

Timeframe: Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

All participants were tasked with pushing a joystick with the hand most affected by PD symptoms in response to monetary incentives. Participants were presented with incentives of low ($5), medium ($10), and high value ($20) on each treatment day, and their movement time in pushing the joystick was measured over the course of 4 visits during the following conditions: Visit 1: Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2: After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3: 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4: After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa). Results reflect participants' response to the medium incentive.

Outcome measures

Outcome measures
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=11 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Joystick Movement Task - Experiment 1 - Medium Incentive
LDR: Chronically Treated - "Practical Off" State
0.21 seconds
Standard Deviation 0.10
Joystick Movement Task - Experiment 1 - Medium Incentive
Baseline - Treatment Naïve Subject
0.24 seconds
Standard Deviation 0.14
Joystick Movement Task - Experiment 1 - Medium Incentive
SDR: Treatment Naïve Subject After Acute L-Dopa
0.20 seconds
Standard Deviation 0.10
Joystick Movement Task - Experiment 1 - Medium Incentive
SDR + LDR: Chronically Treated - After Usual L-Dopa
0.19 seconds
Standard Deviation 0.08

PRIMARY outcome

Timeframe: Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

All participants were tasked with pushing a joystick with the hand most affected by PD symptoms in response to monetary incentives. Participants were presented with incentives of low ($5), medium ($10), and high value ($20) on each treatment day, and their movement time in pushing the joystick was measured over the course of 4 visits during the following conditions: Visit 1: Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2: After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3: 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4: After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa). Results reflect participants' response to the high incentive.

Outcome measures

Outcome measures
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=11 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Joystick Movement Task - Experiment 1 - High Incentive
SDR + LDR: Chronically Treated - After Usual L-Dopa
0.18 seconds
Standard Deviation 0.06
Joystick Movement Task - Experiment 1 - High Incentive
Baseline - Treatment Naïve Subject
0.25 seconds
Standard Deviation 0.23
Joystick Movement Task - Experiment 1 - High Incentive
SDR: Treatment Naïve Subject After Acute L-Dopa
0.20 seconds
Standard Deviation 0.10
Joystick Movement Task - Experiment 1 - High Incentive
LDR: Chronically Treated - "Practical Off" State
0.20 seconds
Standard Deviation 0.09

PRIMARY outcome

Timeframe: Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

Participants were tasked with modulating their grip strength in response to monetary incentives. With the hand most affected by PD symptoms, participants squeezed a dynamometer. Participants were presented with incentives of low ($5), medium ($10), and high value ($20) on each treatment day, and their time in reaching their maximum grip strength was measured over the course of 4 visits during the following conditions: Visit 1. Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2. After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3. 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4. After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa).

Outcome measures

Outcome measures
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=11 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Grip Force Task - Experiment 1 - Low Incentive
Visit 2 - SDR: Treatment Naïve Subject After Acute L-Dopa
0.14 seconds
Standard Deviation 0.07
Grip Force Task - Experiment 1 - Low Incentive
Visit 1 - Baseline - Treatment Naïve Subject
0.14 seconds
Standard Deviation 0.10
Grip Force Task - Experiment 1 - Low Incentive
Visit 3 - LDR: Chronically Treated - "Practical Off" State
0.13 seconds
Standard Deviation 0.09
Grip Force Task - Experiment 1 - Low Incentive
Visit 4 - SDR + LDR: Chronically Treated - After Usual L-Dopa
0.12 seconds
Standard Deviation 0.08

PRIMARY outcome

Timeframe: Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

Participants were tasked with modulating their grip strength in response to monetary incentives. With the hand most affected by PD symptoms, participants squeezed a dynamometer. Participants were presented with incentives of low ($5), medium ($10), and high value ($20) on each treatment day, and their time in reaching their maximum grip strength was measured over the course of 4 visits during the following conditions: Visit 1. Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2. After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3. 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4. After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa).

Outcome measures

Outcome measures
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=11 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Grip Force Task - Experiment 1 - Medium Incentive
Visit 2 - SDR: Treatment Naïve Subject After Acute L-Dopa
0.14 seconds
Standard Deviation 0.08
Grip Force Task - Experiment 1 - Medium Incentive
Visit 4 - SDR + LDR: Chronically Treated - After Usual L-Dopa
0.12 seconds
Standard Deviation 0.07
Grip Force Task - Experiment 1 - Medium Incentive
Visit 1 - Baseline - Treatment Naïve Subject
0.14 seconds
Standard Deviation 0.10
Grip Force Task - Experiment 1 - Medium Incentive
Visit 3 - LDR: Chronically Treated - "Practical Off" State
0.12 seconds
Standard Deviation 0.07

PRIMARY outcome

Timeframe: Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

Participants were tasked with modulating their grip strength in response to monetary incentives. With the hand most affected by PD symptoms, participants squeezed a dynamometer. Participants were presented with incentives of low ($5), medium ($10), and high value ($20) on each treatment day, and their time in reaching their maximum grip strength was measured over the course of 4 visits during the following conditions: Visit 1. Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2. After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3. 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4. After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa).

Outcome measures

Outcome measures
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=11 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Grip Force Task - Experiment 1 - High Incentive
Visit 1 - Baseline - Treatment Naïve Subject
0.14 seconds
Standard Deviation 0.09
Grip Force Task - Experiment 1 - High Incentive
Visit 2 - SDR: Treatment Naïve Subject After Acute L-Dopa
0.13 seconds
Standard Deviation 0.05
Grip Force Task - Experiment 1 - High Incentive
Visit 3 - LDR: Chronically Treated - "Practical Off" State
0.12 seconds
Standard Deviation 0.08
Grip Force Task - Experiment 1 - High Incentive
Visit 4 - SDR + LDR: Chronically Treated - After Usual L-Dopa
0.12 seconds
Standard Deviation 0.08

PRIMARY outcome

Timeframe: Visit 1 at Baseline, Visit 2 up to 2 weeks after baseline, Visit 3 up to 2-4 months after baseline, and Visit 4 up to 4 months after baseline

Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part III, Motor Examination. Scores range from 0 to 86. A higher score indicates worse motor performance. Participants completed this scale at each visit over the course of 4 visits during the following conditions: Visit 1. Baseline prior to chronic treatment initiation (Treatment Naïve Subject); Visit 2. After the initial, standard, acute oral dosage (SDR: Treatment Naïve Subject After Acute LDopa); Visit 3. 2-4 months after start of chronic treatment following Visit 2, stable LDopa treatment (as prescribed by treating physicians), but with no LDopa for 10-12 hours prior to Visit 3 (LDR: Chronically Treated - "Practical Off" State); and Visit 4. After resuming participants' usual physician-prescribed LDopa dose (SDR + LDR: Chronically Treated - After Usual LDopa).

Outcome measures

Outcome measures
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=11 Participants
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part III - Experiment 1
Visit 1 - Baseline - Treatment Naïve Subject
31.45 score on a scale
Standard Deviation 7.46
MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part III - Experiment 1
Visit 4 - SDR + LDR: Chronically Treated - After Usual L-Dopa
14.82 score on a scale
Standard Deviation 7.47
MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part III - Experiment 1
Visit 2 - SDR: Treatment Naïve Subject After Acute L-Dopa
24.36 score on a scale
Standard Deviation 8.15
MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part III - Experiment 1
Visit 3 - LDR: Chronically Treated - "Practical Off" State
18.64 score on a scale
Standard Deviation 6.82

Adverse Events

Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Experiment 2: Primary Outcome (Value Driven Attentional Oculomotor Capture)

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Experiment 1: Primary Outcomes (MDS-UPDRS, Joystick Task, Tapping Speed)
n=12 participants at risk
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and three outcome measures: Tapping Speed Task - Measurement of Bradykinesia; Joystick Movement Task - Measurement of Incentive-Outcome Coupling - Movement Vigor; and completion of MDS-UPDRS. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants included in Experiment 1 were not included in Experiment 2.
Experiment 2: Primary Outcome (Value Driven Attentional Oculomotor Capture)
n=7 participants at risk
Participants will undergo evaluation of the relationship between the LDR and movement vigor. All participants will undergo standard evaluation with standard clinical rating scales and the outcome measure: Grip Strength Task - Measurement of Incentive-Outcome Coupling - Movement Vigor. carbidopa/levodopa, as prescribed by treating physician: There will be 4 measurement states: at baseline prior to chronic treatment initiation (OFF-No LDR); at baseline after a standard, acute oral dose (25/250 carbidopa/L-dopa), referenced in the protocol, but prescribed and provided by their prescribing physician as standard of care initial dosage (ON-No LDR); 2 months after initiation of chronic, stable L-dopa treatment (amounts and sequences as prescribed by treating physicians) but with no L-dopa for 10-12 hours prior to evaluation (Practical OFF- LDR); and after resuming subjects' usual physician-prescribed L-dopa dose (ON-LDR). Participants from Experiment 2 were not included in Experiment 1.
Vascular disorders
pre-syncope
8.3%
1/12 • Number of events 1 • Up to 4 months
0.00%
0/7 • Up to 4 months
Gastrointestinal disorders
vomiting
8.3%
1/12 • Number of events 1 • Up to 4 months
0.00%
0/7 • Up to 4 months

Additional Information

Dr. Roger Albin

University of Michigan

Phone: 734-936-9115

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place