Accidental Falls, Parkinson Disease
Conditions
Keywords
Vitamin D, Parkinson disease, accidental falls
Brief summary
A trial to measure the effects of vitamin D (versus a placebo) on balance, gait, falls, strength, and cognition in persons with Parkinson's disease.
Detailed description
The proposed study is a randomized, double-blinded, placebo controlled intervention trial to measure the effects of vitamin D at (10,000IU/day) versus placebo on balance and falls in Parkinson's disease. The investigators will measure static, dynamic, and ambulatory balance, as well as strength, falls, and cognition before and after 16 weeks of therapy. Dynamic posturography will be used to measure static and ambulatory balance, a device called iMOBILITY will measure a timed up and go, and strength will be measured with the Biodex machine checking knee flexion and extension. Multiple quality of life and cognitive tests will also be performed.
Interventions
DRUGVitamin D3
Vitamin D3 at 10,000 IU a day
DIETARY_SUPPLEMENTcalcium
1000mg calcium daily
OTHERPlacebo
A placebo pill with similar appearance to the vitamin D3 will be given to those in the placebo arm
Sponsors
Oregon Health and Science University
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Parkinson's disease; * ability to ambulate 50 feet; * ability to cooperate with balance testing; * vitamin D level less than 40ng/ml; * balance problems; * ability to walk 50 feet without the help of another person
Exclusion criteria
* MMSE \< 25; * another neurological or orthopedic deficit that in the examiner's opinion would affect testing; * history of renal stones or hypercalcemia; * unwillingness to not be on other vitamin D supplementation during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Strength as Recorded by Measuring Knee Extension Using Biodex (Total Work) | Baseline, 16 weeks | Defined as the total muscular force output for the repetition with the greatest amount of work. The equation for work is: W = F x D. Change score is measurement at 16 weeks minus measurement at baseline. |
| Change in Ambulatory Balance Measured by Instrumented Timed up and go (iTUG) Turn Duration | Baseline and 16 weeks | This is a test that measures ambulatory balance and mobility. The instrumented timed up and go (iTUG) is an average time (seconds) of three trials that involve the participant arising from a chair, walking 25 feet turning around, walking back to the chair, and sitting down. The turn duration is the average time to turn at the end of the 25 foot walk. Longer duration of time (seconds) indicates more rigidity, a proxy measure for ON time in Parkinson's disease. Change score is measurement at 16 weeks minus measurement at baseline. |
| Change in Strength as Recorded by Measuring Knee Flexion Using Biodex (Total Work) | Baseline, 16 weeks | Defined as the total muscular force output for the repetition with the greatest amount of work. The equation for work is: W = F x D. Change score is measurement at 16 weeks minus measurement at baseline. |
| Change in Dynamic Balance as Recorded Using Dynamic Posturography With the Sensory Organization Test (SOT 4-6) | Baseline, 16 weeks | Sensory organization test (SOT) is a form of posturography. which is designed to assess quantitatively an individual's ability to use visual, proprioceptive and vestibular cues to maintain postural stability in stance. The SOT measures sway during 6 scenarios. In 4-6 the base moves and the subject has eyes open, then closed, then the visual surround moves. SOT 4-6 is an average measurement of equilibrium - the average center of gravity sway for each condition. It generates a score of 0 (fall) up to 100 for each scenario and an overall composite score. Change score is measurement at 16 weeks minus measurement at baseline. |
| Change in Static Balance as Recorded Using Dynamic Posturography With the Sensory Organization Test (SOT 1-3) | Baseline, 16 weeks | Sensory organization test (SOT) is a form of posturography. which is designed to assess quantitatively an individual's ability to use visual, proprioceptive and vestibular cues to maintain postural stability in stance. The SOT measures sway during 6 scenarios. In scenarios 1-3 the base is stable and eyes are open, then closed, and then the visual surround moves. SOT 1-3 is an average measurement of equilibrium - the average center of gravity sway for each condition. It generates a score of 0 (fall) up to 100 for each scenario and an overall composite score. Change score is measurement at 16 weeks minus measurement at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life as Recorded Using Quality of Life Scales (PDQ39) | Baseline, 16 weeks | The PDQ39 is a 39 item patient completed survey targeting well-being and functioning in PD. This scale address 8 dimensions (mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication, and bodily discomfort). The PDQ39 dimension scores are on a scale of 0 (Never) to 4 (Always/Cannot Do). Scale scores are summed and range from 0 to 100 with 100 being the maximum level of problems. For a single index figure to characterize the impact of Parkinson's disease upon PD patients (PDSI), all 39 items of the PDQ39 can be summed. The PDQ39 and the use of a PDSI have shown adequate reliability and convergent validity. Change score is measurement at 16 weeks minus baseline measurement, negative scores indicate an improvement in quality of life. |
| Change in Parkinsonism as Measured by the UPDRS | Baseline, 16 weeks | This is the motor subsection of the UPDRS and is a commonly used tool to rate the symptoms of Parkinson's disease. This scale rates from 0 (normal) to 4 (Can barely perform the task) several motor areas including speech, facial expression, tremor, rigidity, hand movements, agility, posture, and gait. A sum score represents motor function with higher values on this scale represent a more severe stage of the disease. Change is measurement at 16 weeks minus baseline measurement, negative scores indicate an improvement in Parkinson's motor symptoms. |
| Change in Cognition (Trail Making Test B-A) | Baseline, 16 weeks | The Trail Making Test (TMT) consists of two parts (A & B) in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The test provides information about visual search speed, scanning, speed of processing, and executive functioning. Part A measures processing speed and part B measures executive functioning. The TMT is time to complete each part of the test in seconds. Higher scores indicate greater impairment. Subtracting part A from part B is theorized to reduce the influence of the working memory and visuospatial demands and, therefore, provides a relatively pure indicator of executive function. Change score is measurement (Part B - Part A) at 16 weeks minus measurement (Part B - Part A) at baseline, negative scores indicate a improvement in executive functioning. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from two large treatment centers in the Pacific Northwest and from the community during the time period 2011 - 2014.
Pre-assignment details
Excluded (n=33) Not meeting criteria (n=32) (16 have vitamin D levels that were too high, 4 hx of renal stones, 3 with a history of tuberculosis, and 9 other) Lost to follow-up (n=1)
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D (Open Label) Will be on high dose vitamin D (10,000 IU daily) and 1000 mg of calcium
Vitamin D: Vitamin D at 10,000 IU a day
calcium: 1000mg calcium daily | 10 |
| Vitamin D Will be on high dose vitamin D (10,000 IU daily) and 1000 mg of calcium
Vitamin D: Vitamin D at 10,000 IU a day
calcium: 1000mg calcium daily | 28 |
| Placebo Will be on placebo and 1000mg of calcium.
calcium: 1000mg calcium daily
Placebo: A placebo pill with similar appearance to the vitamin D will be given to those in the placebo arm | 30 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 |
| Overall Study | Non-Compliance | 1 | 0 | 4 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Vitamin D (Open Label) | Vitamin D | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 70.1 years STANDARD_DEVIATION 8 | 64.5 years STANDARD_DEVIATION 8 | 68.8 years STANDARD_DEVIATION 8.1 | 67.2 years STANDARD_DEVIATION 8.3 |
| Baseline Vitamin D | 14.7 ng/ml STANDARD_DEVIATION 3.86 | 30.21 ng/ml STANDARD_DEVIATION 5.32 | 29.43 ng/ml STANDARD_DEVIATION 6.46 | 27.59 ng/ml STANDARD_DEVIATION 7.78 |
| Falls Self-Report | 5.86 Falls STANDARD_DEVIATION 14.18 | 3.79 Falls STANDARD_DEVIATION 14.85 | 3.05 Falls STANDARD_DEVIATION 7.26 | 3.75 Falls STANDARD_DEVIATION 11.6 |
| Hoehn & Yahr | 2.35 units on a scale STANDARD_DEVIATION 0.34 | 2.48 units on a scale STANDARD_DEVIATION 0.46 | 2.46 units on a scale STANDARD_DEVIATION 0.47 | 2.45 units on a scale STANDARD_DEVIATION 0.44 |
| MoCA | 26.67 units on a scale STANDARD_DEVIATION 1.94 | 24.07 units on a scale STANDARD_DEVIATION 2.91 | 24.86 units on a scale STANDARD_DEVIATION 3 | 24.78 units on a scale STANDARD_DEVIATION 2.93 |
| Region of Enrollment United States | 10 participants | 28 participants | 30 participants | 68 participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 10 Participants | 16 Participants |
| Sex: Female, Male Male | 9 Participants | 23 Participants | 20 Participants | 52 Participants |
| UPDRS | 24.20 units on a scale STANDARD_DEVIATION 11.06 | 22.36 units on a scale STANDARD_DEVIATION 8.56 | 25.3 units on a scale STANDARD_DEVIATION 11.5 | 23.93 units on a scale STANDARD_DEVIATION 10.25 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 10 | 1 / 28 | 2 / 30 |
| serious Total, serious adverse events | 0 / 10 | 0 / 28 | 0 / 30 |
Outcome results
Primary
Change in Ambulatory Balance Measured by Instrumented Timed up and go (iTUG) Turn Duration
This is a test that measures ambulatory balance and mobility. The instrumented timed up and go (iTUG) is an average time (seconds) of three trials that involve the participant arising from a chair, walking 25 feet turning around, walking back to the chair, and sitting down. The turn duration is the average time to turn at the end of the 25 foot walk. Longer duration of time (seconds) indicates more rigidity, a proxy measure for ON time in Parkinson's disease. Change score is measurement at 16 weeks minus measurement at baseline.
Time frame: Baseline and 16 weeks
Population: Missing data N=14, test not performed due to either participant fatigue (N = 2) or mechanical/computer issues (N = 12).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Open Label) | Change in Ambulatory Balance Measured by Instrumented Timed up and go (iTUG) Turn Duration | 0.32 seconds | Standard Deviation 0.25 |
| Vitamin D | Change in Ambulatory Balance Measured by Instrumented Timed up and go (iTUG) Turn Duration | 0.09 seconds | Standard Deviation 0.54 |
| Placebo | Change in Ambulatory Balance Measured by Instrumented Timed up and go (iTUG) Turn Duration | -0.07 seconds | Standard Deviation 0.62 |
p-value: 0.308ANOVA
Primary
Change in Dynamic Balance as Recorded Using Dynamic Posturography With the Sensory Organization Test (SOT 4-6)
Sensory organization test (SOT) is a form of posturography. which is designed to assess quantitatively an individual's ability to use visual, proprioceptive and vestibular cues to maintain postural stability in stance. The SOT measures sway during 6 scenarios. In 4-6 the base moves and the subject has eyes open, then closed, then the visual surround moves. SOT 4-6 is an average measurement of equilibrium - the average center of gravity sway for each condition. It generates a score of 0 (fall) up to 100 for each scenario and an overall composite score. Change score is measurement at 16 weeks minus measurement at baseline.
Time frame: Baseline, 16 weeks
Population: Missing data N=3, test not performed due to participant fatigue (N = 2) or computer/mechanical error (N = 1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Open Label) | Change in Dynamic Balance as Recorded Using Dynamic Posturography With the Sensory Organization Test (SOT 4-6) | -1.56 units on a scale | Standard Deviation 11.91 |
| Vitamin D | Change in Dynamic Balance as Recorded Using Dynamic Posturography With the Sensory Organization Test (SOT 4-6) | 2.272 units on a scale | Standard Deviation 12.63 |
| Placebo | Change in Dynamic Balance as Recorded Using Dynamic Posturography With the Sensory Organization Test (SOT 4-6) | -1.89 units on a scale | Standard Deviation 14.23 |
Primary
Change in Static Balance as Recorded Using Dynamic Posturography With the Sensory Organization Test (SOT 1-3)
Sensory organization test (SOT) is a form of posturography. which is designed to assess quantitatively an individual's ability to use visual, proprioceptive and vestibular cues to maintain postural stability in stance. The SOT measures sway during 6 scenarios. In scenarios 1-3 the base is stable and eyes are open, then closed, and then the visual surround moves. SOT 1-3 is an average measurement of equilibrium - the average center of gravity sway for each condition. It generates a score of 0 (fall) up to 100 for each scenario and an overall composite score. Change score is measurement at 16 weeks minus measurement at baseline.
Time frame: Baseline, 16 weeks
Population: Missing data N=2, test not performed due to participant fatigue.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Open Label) | Change in Static Balance as Recorded Using Dynamic Posturography With the Sensory Organization Test (SOT 1-3) | -3.25 units on a scale | Standard Deviation 2.93 |
| Vitamin D | Change in Static Balance as Recorded Using Dynamic Posturography With the Sensory Organization Test (SOT 1-3) | 2.05 units on a scale | Standard Deviation 8.85 |
| Placebo | Change in Static Balance as Recorded Using Dynamic Posturography With the Sensory Organization Test (SOT 1-3) | 1.78 units on a scale | Standard Deviation 21.66 |
p-value: 0.699ANOVA
Primary
Change in Strength as Recorded by Measuring Knee Extension Using Biodex (Total Work)
Defined as the total muscular force output for the repetition with the greatest amount of work. The equation for work is: W = F x D. Change score is measurement at 16 weeks minus measurement at baseline.
Time frame: Baseline, 16 weeks
Population: Missing data N=4, test not performed due to participant fatigue (N = 2), mechanical/computer issues (N = 1), illness of operator (N = 1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Open Label) | Change in Strength as Recorded by Measuring Knee Extension Using Biodex (Total Work) | 18.11 foot pounds | Standard Deviation 66.65 |
| Vitamin D | Change in Strength as Recorded by Measuring Knee Extension Using Biodex (Total Work) | 23.33 foot pounds | Standard Deviation 83.16 |
| Placebo | Change in Strength as Recorded by Measuring Knee Extension Using Biodex (Total Work) | 17.49 foot pounds | Standard Deviation 32.02 |
p-value: 0.949ANOVA
Primary
Change in Strength as Recorded by Measuring Knee Flexion Using Biodex (Total Work)
Defined as the total muscular force output for the repetition with the greatest amount of work. The equation for work is: W = F x D. Change score is measurement at 16 weeks minus measurement at baseline.
Time frame: Baseline, 16 weeks
Population: Missing data N=4, test not performed due to participant fatigue (N = 2), mechanical/computer issues (N = 1), illness of operator (N = 1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Open Label) | Change in Strength as Recorded by Measuring Knee Flexion Using Biodex (Total Work) | 83.07 foot pounds | Standard Deviation 117.4 |
| Vitamin D | Change in Strength as Recorded by Measuring Knee Flexion Using Biodex (Total Work) | 6.89 foot pounds | Standard Deviation 176.4 |
| Placebo | Change in Strength as Recorded by Measuring Knee Flexion Using Biodex (Total Work) | 35.19 foot pounds | Standard Deviation 80.74 |
p-value: 0.419ANOVA
Secondary
Change in Cognition (Trail Making Test B-A)
The Trail Making Test (TMT) consists of two parts (A & B) in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The test provides information about visual search speed, scanning, speed of processing, and executive functioning. Part A measures processing speed and part B measures executive functioning. The TMT is time to complete each part of the test in seconds. Higher scores indicate greater impairment. Subtracting part A from part B is theorized to reduce the influence of the working memory and visuospatial demands and, therefore, provides a relatively pure indicator of executive function. Change score is measurement (Part B - Part A) at 16 weeks minus measurement (Part B - Part A) at baseline, negative scores indicate a improvement in executive functioning.
Time frame: Baseline, 16 weeks
Population: Missing data (N = 8) due to scheduling difficulties (N = 3), neuropsychological administration errors (N = 2), patient discontinuing (N = 1), maximum time allowance met and discontinued test (N = 2).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Open Label) | Change in Cognition (Trail Making Test B-A) | 8.00 seconds | Standard Deviation 30.89 |
| Vitamin D | Change in Cognition (Trail Making Test B-A) | 12.13 seconds | Standard Deviation 49.83 |
| Placebo | Change in Cognition (Trail Making Test B-A) | -17.33 seconds | Standard Deviation 74.7 |
p-value: 0.253ANOVA
Secondary
Change in Parkinsonism as Measured by the UPDRS
This is the motor subsection of the UPDRS and is a commonly used tool to rate the symptoms of Parkinson's disease. This scale rates from 0 (normal) to 4 (Can barely perform the task) several motor areas including speech, facial expression, tremor, rigidity, hand movements, agility, posture, and gait. A sum score represents motor function with higher values on this scale represent a more severe stage of the disease. Change is measurement at 16 weeks minus baseline measurement, negative scores indicate an improvement in Parkinson's motor symptoms.
Time frame: Baseline, 16 weeks
Population: Missing data (N = 2), invalid sum due to missing rating (N = 1), not completed due to scheduling conflicts (N = 1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Open Label) | Change in Parkinsonism as Measured by the UPDRS | 0.25 units on a scale | Standard Deviation 8.33 |
| Vitamin D | Change in Parkinsonism as Measured by the UPDRS | 0.48 units on a scale | Standard Deviation 5.6 |
| Placebo | Change in Parkinsonism as Measured by the UPDRS | -0.18 units on a scale | Standard Deviation 9.73 |
p-value: 0.957ANOVA
Secondary
Change in Quality of Life as Recorded Using Quality of Life Scales (PDQ39)
The PDQ39 is a 39 item patient completed survey targeting well-being and functioning in PD. This scale address 8 dimensions (mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication, and bodily discomfort). The PDQ39 dimension scores are on a scale of 0 (Never) to 4 (Always/Cannot Do). Scale scores are summed and range from 0 to 100 with 100 being the maximum level of problems. For a single index figure to characterize the impact of Parkinson's disease upon PD patients (PDSI), all 39 items of the PDQ39 can be summed. The PDQ39 and the use of a PDSI have shown adequate reliability and convergent validity. Change score is measurement at 16 weeks minus baseline measurement, negative scores indicate an improvement in quality of life.
Time frame: Baseline, 16 weeks
Population: Missing data (N = 3), patient forgot form and did not return mailed form (N = 3).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Open Label) | Change in Quality of Life as Recorded Using Quality of Life Scales (PDQ39) | -0.16 units on a scale | Standard Deviation 0.96 |
| Vitamin D | Change in Quality of Life as Recorded Using Quality of Life Scales (PDQ39) | -0.02 units on a scale | Standard Deviation 0.47 |
| Placebo | Change in Quality of Life as Recorded Using Quality of Life Scales (PDQ39) | -0.14 units on a scale | Standard Deviation 0.79 |
p-value: 0.793ANOVA