Trial Outcomes & Findings for Prism Adaptation Treatment of Parkinson's Disease (NCT NCT02380859)

NCT ID: NCT02380859

Last Updated: 2019-03-25

Results Overview

The participant stood on the platform in front of a monitor. Nine squares were presented on the monitor representing locations relative to the upright starting position: one in the centre of the screen (upright) and the remaining eight forming an ellipse around the central square. The participant's COG was indicated on the screen by the position of a stick figure avatar. At the beginning of each trial the participant was instructed to stand upright, keeping the COG cursor over the central target. A circular target appeared in one of eight other targets. The participant was required to move the COG cursor towards the second target as quickly and as accurately as possible by leaning their body while keeping their feet in the same location, and to then hold a position as close to the target as possible. Reacting times were recorded for 8 trials per location. Mean change (post-pre) in seconds

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 32 participants
• Primary outcome timeframe: Baseline (Day 0) and Day 15
• Results posted on: 2019-03-25

Participant Flow

There was a protocol violation in our intended randomization procedure in that participants were randomized to treatment or control groups with replacement instead of without replacement. This resulted in uneven group numbers, rather than the equal group numbers that was intended.

Participant milestones

Measure	Real Prism Adaptation Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation Participants were randomized to placebo lenses that distorted vision without vertical shift.
Overall Study STARTED	19	13
Overall Study COMPLETED	17	13
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	Real Prism Adaptation Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation Participants were randomized to placebo lenses that distorted vision without vertical shift.
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

Prism Adaptation Treatment of Parkinson's Disease

Baseline characteristics by cohort

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to treatment prisms, designed to shift vertical orientation slightly by 1.5 degrees	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift.	Total n=30 Participants Total of all reporting groups
Age, Continuous	70.7 years STANDARD_DEVIATION 7.7 • n=5 Participants	68.3 years STANDARD_DEVIATION 8.2 • n=7 Participants	69.5 years STANDARD_DEVIATION 7.9 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	6 Participants n=7 Participants	18 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	17 Participants n=5 Participants	13 Participants n=7 Participants	30 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	12 participants n=7 Participants	24 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0) and Day 15

The participant stood on the platform in front of a monitor. Nine squares were presented on the monitor representing locations relative to the upright starting position: one in the centre of the screen (upright) and the remaining eight forming an ellipse around the central square. The participant's COG was indicated on the screen by the position of a stick figure avatar. At the beginning of each trial the participant was instructed to stand upright, keeping the COG cursor over the central target. A circular target appeared in one of eight other targets. The participant was required to move the COG cursor towards the second target as quickly and as accurately as possible by leaning their body while keeping their feet in the same location, and to then hold a position as close to the target as possible. Reacting times were recorded for 8 trials per location. Mean change (post-pre) in seconds

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Postural Control - Reaction Time on the Limits of Stability Test (Smart Equitest Balance Master System)	0.09 Seconds Standard Deviation 0.29	-0.02 Seconds Standard Deviation 0.36

PRIMARY outcome

Timeframe: Baseline (Day 0) and Day 15

Population: Average change time; mean change (post-pre) meters per second

The participant stood on the platform in front of a monitor. Nine squares were presented on the monitor representing locations relative to the upright starting position: one in the centre of the screen (upright) and the remaining eight forming an ellipse around the central square. The participant's COG was indicated on the screen by the position of a stick figure avatar. At the beginning of each trial the participant was instructed to stand upright, keeping the COG cursor over the central target. A circular target appeared in one of eight other targets. The participant was required to move the COG cursor towards the second target as quickly and as accurately as possible by leaning their body while keeping their feet in the same location, and to then hold a position as close to the target as possible. Maximum velocity was recorded for 8 trials per location.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Postural Control - Maximum Velocity on the Limits of Stability Test (Smart Equitest Balance Master System)	0.54 meters per second Standard Deviation 0.67	0.11 meters per second Standard Deviation 0.62

PRIMARY outcome

Timeframe: Baseline (Day 0) and Day 15

Population: Average change in Maximum Extension between baseline and day 15

The participant stood on the platform in front of a monitor. Nine squares were presented on the monitor representing locations relative to the upright starting position: one in the centre of the screen (upright) and the remaining eight forming an ellipse around the central square. The participant's COG was indicated on the screen by the position of a stick figure avatar. At the beginning of each trial the participant was instructed to stand upright, keeping the COG cursor over the central target. A circular target appeared in one of eight other targets. The participant was required to move the COG cursor towards the second target as quickly and as accurately as possible by leaning their body while keeping their feet in the same location, and to then hold a position as close to the target as possible. Maximum extension of the COG over the feet was recorded for 8 trials per location.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Postural Control - Maximum Extension on the Limits of Stability Test (Smart Equitest Balance Master System)	3.0 meters Standard Deviation 9.8	0.63 meters Standard Deviation 10.4

PRIMARY outcome

Timeframe: Baseline (Day 0) and Day 15

The participant is asked to maintain an upright posture under six different conditions of sensory feedback:

• Condition 1:Normal vision, fixed support
• Condition 2:Absent vision, fixed support
• Condition 3:Sway-referenced vision, fixed support
• Condition 4:Normal vision, sway-referenced support
• Condition 5:Absent vision, sway-referenced support
• Condition 6:Sway-referenced vision, sway-referenced support

The equilibrium score for each condition compares the subject's anterior/posterior (AP) sway during each trial to the theoretical sway stability limit of 12.5 degrees. A composite equilibrium score (0-100, higher score indicates better outcome) quantifies the overall COG sway or postural stability across the sensory conditions and is calculated by:

• Independently averaging the score for conditions 1 and 2;
• Adding these two scores to the equilibrium scores from each trial of sensory conditions 3, 4, 5, and 6; and
• Dividing that sum by the total number of trials.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Postural Control - Composite Score on the Sensory Organisation Test SMART EquiTest Balance Master	4.3 change in percentage Standard Deviation 9.2	2.5 change in percentage Standard Deviation 10.4

PRIMARY outcome

Timeframe: Baseline (Day 0) and Day 15

The participant is asked to maintain an upright posture under different conditions of sensory feedback. Proprioceptive feedback to the feet and joints is manipulated by allowing the platform to tilt to directly follow the participant's anteroposterior body sway (constant proprioception) or by maintaining the standing platform in a fixed horizontal position (normal proprioceptive feedback). Visual feedback is provided by asking the participant to close their eyes (no visual feedback), asking the participant to open their eyes and allowing the visual surround to tilt directly following the participant's anterioposterior body sway (constant visual feedback), or by asking the participant to keep their eyes open and maintaining the visual surround in a fixed position (normal visual feedback). Forward-backward displacement of COG is recorded in degrees.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Postural Control - Forward-backward Displacement of Centre of Gravity on the Sensory Organisation Test SMART EquiTest Balance Master	0.05 Degrees Standard Deviation 1.3	-0.12 Degrees Standard Deviation 0.62

PRIMARY outcome

Timeframe: Baseline (Day 0) and Day 15

The MCT assesses the ability of the automatic motor system to quickly recover following an unexpected external disturbance. Sequences of small, medium or large platform translations (scaled to the patient's height) in forward and backward directions elicit automatic postural responses. Translation of the surface in one horizontal direction results in displacement of the COG away from center in the opposite direction relative to the base of support. To restore normal balance, a quick movement of the COG back to the center position is required. A composite latency value is provided as the time in milliseconds between the force plate translation and the patient's active corrective responses, averaged across all translation sizes and directions.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Postural Control - Composite Latency Score on the Motor Control Test	1.9 ms Standard Deviation 13.6	2.1 ms Standard Deviation 23.1

PRIMARY outcome

Timeframe: Baseline (Day 0) and Day 15

Berg Balance Scale. This 14-item test assesses balance during different tasks. Items consist of specific items such as standing with eyes closed, retrieving an object from the floor, and turning to look behind. The assessor rates the patient's performance from 0 ("lowest level of function") to 4 ("highest level of function") and a total is calculated out of a maximum score of 56.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Postural Control - Composite Latency Score on the Berg Balance Scale	0.38 scores on a scale Standard Deviation 2.4	-0.69 scores on a scale Standard Deviation 2.4

SECONDARY outcome

Timeframe: Baseline (Day 0) and Day 15

The WA quantifies characteristics of gait as the patient walks across the length of the force plate. The test characterizes steady state gait by having the patient begin well behind and continuing beyond the force plate. Measured parameters are average step width, average step length, speed and step length symmetry.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Gait - Step Length on the Walk Across Test (SMART Equitest Balance Master)	-3.0 cm Standard Deviation 30.4	-4.1 cm Standard Deviation 32.6

SECONDARY outcome

Timeframe: Baseline (Day 0) and Day 15

The WA quantifies characteristics of gait as the patient walks across the length of the force plate. The test characterizes steady state gait by having the patient begin well behind and continuing beyond the force plate. Measured parameters are average step width, average step length, speed and step length symmetry.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Gait - Step Speed in the Walk Across (SMART Equitest Balance Master)	5.0 cm/s Standard Deviation 19.5	1.3 cm/s Standard Deviation 22.0

SECONDARY outcome

Timeframe: Baseline (Day 0) and Day 15

Timed Up and Go Test (TUG). Patients are seated in a chair and instructed to stand up, walk three meters, turn around, walk back, and sit down. The time (in seconds) is recorded.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Gait - Timed Up and Go Task	-1.8 seconds Standard Deviation 4.8	-0.25 seconds Standard Deviation 1.3

SECONDARY outcome

Timeframe: Baseline (Day 0) and Day 15

Functional Gait Assessment. This 10-item test assesses dynamic balance and postural stability during gait. Items consist of specific walking tasks such as stepping over an obstacle, changing speed of walking upon the assessor's instruction, and walking backwards. The assessor scores the patient's performance from 0 ("severe impairment") to 3 ("normal") and a total is calculated out of 30.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Gait - Functional Gait Assessment	1.8 scores on a scale Standard Deviation 4.8	1.0 scores on a scale Standard Deviation 1.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 0) and Day 15

Average change in score relating to new freezing of gate utilizing the New Freezing of Gait Questionnaire. This nine-item questionnaire detects and evaluates the impact and severity of freezing of gait on locomotion and daily activities. Items are scored from 0 or 1 to 3 or 4, with higher numbers indicating greater impact and severity. A total score out of 28 is calculated.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Activities of Daily Living - New Freezing of Gait	-0.19 scores on a scale Standard Deviation 4.19	-5.0 scores on a scale Standard Deviation 1.40

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 0) and Day 15

Average change in score evaluated using the Falls Efficiency Scale. This ten-item questionnaire asks people to rate their confidence in performing daily activities without falling. Responses are given on a scale from 0 ("very confident") to 10 ("not very confident") and a total score out of 100 is computed.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Activities of Daily Living - Falls Efficiency	2.16 scores on a scale Standard Deviation 10.11	-10.70 scores on a scale Standard Deviation 2.97

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 0) and Day 15

Activities-specific Balance Confidence Scale. This 16-item questionnaire is similar to the Falls Efficiency Scale, but has greater sensitivity to gait impairments in more ambulatory patients. Responses are given on a scale from 0 ("very confident") to 10 "not very confident") and a total score out of 100 is computed.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Activities of Daily Living - Activity-specific Balance Confidence Scale	-0.57 scores on a scale Standard Deviation 10.7	-5.8 scores on a scale Standard Deviation 12.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 0) and Day 15

Parkinson's Disease Questionnaire (PDQ-39), mobility and activities of daily living sections. This 39-item questionnaire is the most widely-used Parkinson's Disease specific measure of health and daily function. Participants indicate the extent to which they have experienced problems with different aspects of mobility and self-care. Each item is scored from 0 ("never have problems") to 4 ("always have problems"), and a percentage is calculated. In addition to the total score, the mobility (questions 1-10) and activities of daily living (questions 11-16) sub-sections can be analysed separately to assess changes in these specific outcomes. The responses are summed and scored as a percentage. We analysed the percentage scores for the mobility sub-section, the activities of daily living sub-section, and the total percentage. Higher values indicate worse outcome.

Outcome measures

Measure	Real Prism Adaptation n=17 Participants Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 Participants Participants were randomized to placebo lenses that distorted vision without vertical shift
Change in Activities of Daily Living - Parkinson's Disease Questionnaire Mobility subscale (%)	-0.89 percentage Standard Deviation 8.83	-2.50 percentage Standard Deviation 13.27
Change in Activities of Daily Living - Parkinson's Disease Questionnaire Activities of daily living subscale (%)	-0.63 percentage Standard Deviation 12.48	3.8 percentage Standard Deviation 11.2
Change in Activities of Daily Living - Parkinson's Disease Questionnaire Total (%)	0.21 percentage Standard Deviation 6.13	1.78 percentage Standard Deviation 8.27

Adverse Events

Real Prism Adaptation

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Sham Prism Adaptation

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Real Prism Adaptation n=17 participants at risk Participants were randomized to undergo treatment that involved adaptation to 15º upward shifts in vision.	Sham Prism Adaptation n=13 participants at risk Participants were randomized to placebo lenses that distorted vision without vertical shift.
Nervous system disorders Concusion	0.00% 0/17 • From consent until study completion, approximately 3 months.	7.7% 1/13 • Number of events 1 • From consent until study completion, approximately 3 months.
Nervous system disorders Freezing	5.9% 1/17 • Number of events 1 • From consent until study completion, approximately 3 months.	0.00% 0/13 • From consent until study completion, approximately 3 months.
Nervous system disorders Blurry Vision/Dizzy	0.00% 0/17 • From consent until study completion, approximately 3 months.	7.7% 1/13 • Number of events 1 • From consent until study completion, approximately 3 months.

Additional Information

Stephen L. Lee, MD PhD

Dartmouth-Hitchcock Medical Center

Phone: 603-650-5104

Email: stephen.l.lee@hitchcock.org

Results disclosure agreements

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