Parkinson Disease
Conditions
Keywords
freezing of gait
Brief summary
Freezing of gait is a late stage complication of Parkinson's disease in which patients note that their feet feel stuck or glued to the ground. This can lead to imbalance and falls and the secondary complications that can result from falls such as fractures and hospitalizations. While levodopa can help freezing of gait in some patients, it does not help in all, and the dose needed to treat freezing may be limited by side effects of the medications. Currently there are no treatments targeted towards freezing of gait and the goal of this research is to see if Modafinil could be one such drug to help freezing of gait in Parkinson's disease.
Detailed description
Freezing of gait is a late stage complication of Parkinson's disease in which patients note that their feet feel stuck or glued to the ground. This can lead to imbalance and falls and the secondary complications that can result from falls such as fractures and hospitalizations. While levodopa can help freezing of gait in some patients, it does not help in all, and the dose needed to treat freezing may be limited by side effects of the medications. Currently there are no treatments targeted towards freezing of gait and the goal of this research is to see if Modafinil could be one such drug to help freezing of gait in Parkinson's disease. Approximately 20 subjects aged 18 or older with idiopathic Parkinson's disease with freezing of gait will be asked to enroll in the study from the patient population in the movement disorders clinic at the University of Arkansas for Medical Sciences (UAMS). Subjects will be assigned randomly 1:1 to an early start and delayed start arm of the study. In the early start arm subjects will receive 24 weeks of 50 mg oral daily Modafinil while subjects in the delayed start arm will receive 12 weeks of placebo followed by 12 weeks of 50 mg oral daily Modafinil. Assessments will be performed prior to initiation of medication at the screening visit, as well as at 12 weeks of the treatment phase. The assessments will include questionnaires to determine the frequency and severity of freezing of gait, level of mood, anxiety and apathy and quality of life, physical examination and tests of cognitive function. Objective assessment of patients walking will be conducted using a pressure sensor impregnated mat at each visit.
Interventions
DRUGmodafinil 50mg
1 capsule oral daily
DRUGPlacebo oral capsule
1 capsule oral daily
Sponsors
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, placebo-controlled delayed start
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of idiopathic PD on UK brain bank criteria. * Presence of FOG based on objective assessment by the movement disorders neurologist. * FOG-Q score \> 8. * Stable PD therapy (including medications and stimulation) for a period of 3 months prior to trial enrollment. * Age ≥ 50 years.
Exclusion criteria
* Patients on antidopaminergic medications for a period of less than 1 year from date of enrollment. * Patients who may require adjustment of their PD medications over the 6 month period of the trial. * History of allergic reactions to Modafinil or armodafinil. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, mitral valve prolapse, left ventricular hypertrophy, chronic obstructive pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements. * Individuals who are pregnant or breastfeeding * Non-english speaking individuals who are unable to complete the questionnaires and other assessments in English and/or follow instructions in English.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline Freezing of Gait (FOG) After First 12 Weeks of Treatment, as Measured by the Giladi Freezing of Gait Questionnaire (FOG-Q). | 12 weeks | The freezing of gait questionnaire (FOG-Q) was administered by a movement disorders neurologist at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The FOG-Q scores 6 items between 0 and 4, for a total score of 24; higher values indicate worse FOG. |
| Mean Change From Baseline Stride Length After 12 Weeks on Treatment, as Measured Using an Instrumented Gait Mat. | 12 weeks | Participants walked on a 20 foot instrumented gait mat for a total of 80 feet, first at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The stride length values usually range between 0 and 160 centimeters (the maximum stride length we have seen in an aging healthy population); lower values typically indicate more shuffling gait and have been associated with greater gait instability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Motor Function After 12 Weeks on Treatment, as Measured by the Unified Parkinson's Disease Rating Scale Motor Score (UPDRS-III). | 12 weeks | For each participant, the Unified Parkinson's disease Rating scale (UPDRS) was administered by a movement disorders neurologist. The scale was first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The motor subscale of the UPDRS takes integer values between 0 and 4 for each of the 27 items for a total maximum score of 108; higher values indicate worse motor function. |
| Mean Change From Baseline Quality of Life After 12 Weeks on Treatment, as Measured by the Parkinson's Disease Questionnaire-39 (PDQ-39). | 12 weeks | For each participant, the Parkinson's Disease Questionnaire (PDQ-39) was self-administered by participants. The questionnaire was first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The PDQ-39 scores takes integer values between 0 and 4, for each of the 39 items for a total maximum score of 156; higher values indicate worse quality of life. |
| Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the REM Sleep Behavior Disorder Questionnaire (RBD-Q). | 12 weeks | For each participant, the REM sleep behavior disorder questionnaire (RBD-Q) was self-administered by participants. The questionnaires were first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The RBD-Q score takes integer values between 0 and 1, for each of the 13 item yes/no questions for a total maximum score of 13; higher values indicate worse sleep behavior disorder. |
| Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the Epworth Sleepiness Scale (ESS). | 12 weeks | For each participant, the Epworth Sleepiness Scale (ESS) questionnaires was self-administered by participants. The questionnaires were first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The ESS takes integer values between 0 and 3, for each of the 8 items for a total maximum score of 24; higher values indicate more daytime sleepiness. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Early-start 24 weeks of modafinil 50 mg oral daily
modafinil 50mg: 1 capsule oral daily | 12 |
| Delayed-start 12 weeks of oral placebo followed by 12 weeks of modafinil 50 mg oral daily
modafinil 50mg: 1 capsule oral daily
Placebo oral capsule: 1 capsule oral daily | 9 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First 12 Weeks (Placebo vs Modafinil) | Withdrawal by Subject | 0 | 2 |
| Last 12 Weeks (Drug for All Subjects) | Physician Decision | 1 | 0 |
| Last 12 Weeks (Drug for All Subjects) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Early-start | Delayed-start | Total |
|---|---|---|---|
| Age, Continuous | 71.6 years STANDARD_DEVIATION 6.3 | 72.9 years STANDARD_DEVIATION 5.3 | 72.1 years STANDARD_DEVIATION 5.8 |
| Epworth Sleepiness Scale (ESS) score | 10.3 units on a scale STANDARD_DEVIATION 2.9 | 10.1 units on a scale STANDARD_DEVIATION 4.6 | 10.2 units on a scale STANDARD_DEVIATION 3.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 9 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Freezing of Gait Questionnaire (FOG-Q) | 13.8 units on a scale STANDARD_DEVIATION 2.5 | 14.4 units on a scale STANDARD_DEVIATION 1.7 | 14.0 units on a scale STANDARD_DEVIATION 2.2 |
| Gait stride length (cm) | 69.8 cms STANDARD_DEVIATION 30.4 | 82.2 cms STANDARD_DEVIATION 27.3 | 75.1 cms STANDARD_DEVIATION 29.1 |
| motor Unified Parkinson's Disease Rating Scale (UPDRS) score | 37.7 units on a scale STANDARD_DEVIATION 5.9 | 38.0 units on a scale STANDARD_DEVIATION 8.3 | 37.8 units on a scale STANDARD_DEVIATION 6.9 |
| Parkinson's Disease Questionnaire-39 (PDQ-39) | 59.8 units on a scale STANDARD_DEVIATION 21.1 | 60.7 units on a scale STANDARD_DEVIATION 21.3 | 60.1 units on a scale STANDARD_DEVIATION 20.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 9 Participants | 21 Participants |
| Region of Enrollment United States | 12 participants | 9 participants | 21 participants |
| REM sleep Behavior Disorder Questionnaire (RBD-Q) | 5.1 units on a scale STANDARD_DEVIATION 3.5 | 5.3 units on a scale STANDARD_DEVIATION 2.9 | 5.2 units on a scale STANDARD_DEVIATION 3.2 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 9 |
| other Total, other adverse events | 12 / 12 | 9 / 9 |
| serious Total, serious adverse events | 1 / 12 | 0 / 9 |
Outcome results
Primary
Mean Change From Baseline Freezing of Gait (FOG) After First 12 Weeks of Treatment, as Measured by the Giladi Freezing of Gait Questionnaire (FOG-Q).
The freezing of gait questionnaire (FOG-Q) was administered by a movement disorders neurologist at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The FOG-Q scores 6 items between 0 and 4, for a total score of 24; higher values indicate worse FOG.
Time frame: 12 weeks
Population: Participants that completed the placebo controlled portion of the study (first 12 weeks of the study)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early-start | Mean Change From Baseline Freezing of Gait (FOG) After First 12 Weeks of Treatment, as Measured by the Giladi Freezing of Gait Questionnaire (FOG-Q). | 0 weeks (Baseline) | 13.75 units on a scale | Standard Deviation 2.53 |
| Early-start | Mean Change From Baseline Freezing of Gait (FOG) After First 12 Weeks of Treatment, as Measured by the Giladi Freezing of Gait Questionnaire (FOG-Q). | 12 weeks | 14.42 units on a scale | Standard Deviation 4.03 |
| Delayed-start | Mean Change From Baseline Freezing of Gait (FOG) After First 12 Weeks of Treatment, as Measured by the Giladi Freezing of Gait Questionnaire (FOG-Q). | 0 weeks (Baseline) | 14.57 units on a scale | Standard Deviation 1.62 |
| Delayed-start | Mean Change From Baseline Freezing of Gait (FOG) After First 12 Weeks of Treatment, as Measured by the Giladi Freezing of Gait Questionnaire (FOG-Q). | 12 weeks | 13.43 units on a scale | Standard Deviation 1.9 |
Primary
Mean Change From Baseline Stride Length After 12 Weeks on Treatment, as Measured Using an Instrumented Gait Mat.
Participants walked on a 20 foot instrumented gait mat for a total of 80 feet, first at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The stride length values usually range between 0 and 160 centimeters (the maximum stride length we have seen in an aging healthy population); lower values typically indicate more shuffling gait and have been associated with greater gait instability.
Time frame: 12 weeks
Population: Participants that completed the placebo controlled portion of the study (first 12 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early-start | Mean Change From Baseline Stride Length After 12 Weeks on Treatment, as Measured Using an Instrumented Gait Mat. | 0 weeks (baseline) | 69.78 cms | Standard Deviation 30.37 |
| Early-start | Mean Change From Baseline Stride Length After 12 Weeks on Treatment, as Measured Using an Instrumented Gait Mat. | 12 weeks | 64.04 cms | Standard Deviation 33.55 |
| Delayed-start | Mean Change From Baseline Stride Length After 12 Weeks on Treatment, as Measured Using an Instrumented Gait Mat. | 0 weeks (baseline) | 90.13 cms | Standard Deviation 14.53 |
| Delayed-start | Mean Change From Baseline Stride Length After 12 Weeks on Treatment, as Measured Using an Instrumented Gait Mat. | 12 weeks | 88.97 cms | Standard Deviation 15.91 |
Secondary
Mean Change From Baseline in Motor Function After 12 Weeks on Treatment, as Measured by the Unified Parkinson's Disease Rating Scale Motor Score (UPDRS-III).
For each participant, the Unified Parkinson's disease Rating scale (UPDRS) was administered by a movement disorders neurologist. The scale was first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The motor subscale of the UPDRS takes integer values between 0 and 4 for each of the 27 items for a total maximum score of 108; higher values indicate worse motor function.
Time frame: 12 weeks
Population: Subjects who completed the first 12 weeks of the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early-start | Mean Change From Baseline in Motor Function After 12 Weeks on Treatment, as Measured by the Unified Parkinson's Disease Rating Scale Motor Score (UPDRS-III). | 0 weeks (baseline) | 37.71 units on a scale | Standard Deviation 5.95 |
| Early-start | Mean Change From Baseline in Motor Function After 12 Weeks on Treatment, as Measured by the Unified Parkinson's Disease Rating Scale Motor Score (UPDRS-III). | 12 weeks | 37.25 units on a scale | Standard Deviation 10.02 |
| Delayed-start | Mean Change From Baseline in Motor Function After 12 Weeks on Treatment, as Measured by the Unified Parkinson's Disease Rating Scale Motor Score (UPDRS-III). | 0 weeks (baseline) | 39.00 units on a scale | Standard Deviation 9.11 |
| Delayed-start | Mean Change From Baseline in Motor Function After 12 Weeks on Treatment, as Measured by the Unified Parkinson's Disease Rating Scale Motor Score (UPDRS-III). | 12 weeks | 34.36 units on a scale | Standard Deviation 9.07 |
Secondary
Mean Change From Baseline Quality of Life After 12 Weeks on Treatment, as Measured by the Parkinson's Disease Questionnaire-39 (PDQ-39).
For each participant, the Parkinson's Disease Questionnaire (PDQ-39) was self-administered by participants. The questionnaire was first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The PDQ-39 scores takes integer values between 0 and 4, for each of the 39 items for a total maximum score of 156; higher values indicate worse quality of life.
Time frame: 12 weeks
Population: Participants that completed the placebo controlled portion of the study (first 12 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early-start | Mean Change From Baseline Quality of Life After 12 Weeks on Treatment, as Measured by the Parkinson's Disease Questionnaire-39 (PDQ-39). | 0 weeks (baseline) | 59.8 units on a scale | Standard Deviation 21.1 |
| Early-start | Mean Change From Baseline Quality of Life After 12 Weeks on Treatment, as Measured by the Parkinson's Disease Questionnaire-39 (PDQ-39). | 12 weeks | 62.6 units on a scale | Standard Deviation 17.5 |
| Delayed-start | Mean Change From Baseline Quality of Life After 12 Weeks on Treatment, as Measured by the Parkinson's Disease Questionnaire-39 (PDQ-39). | 12 weeks | 63.3 units on a scale | Standard Deviation 23.5 |
| Delayed-start | Mean Change From Baseline Quality of Life After 12 Weeks on Treatment, as Measured by the Parkinson's Disease Questionnaire-39 (PDQ-39). | 0 weeks (baseline) | 65.7 units on a scale | Standard Deviation 21.2 |
Secondary
Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the Epworth Sleepiness Scale (ESS).
For each participant, the Epworth Sleepiness Scale (ESS) questionnaires was self-administered by participants. The questionnaires were first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The ESS takes integer values between 0 and 3, for each of the 8 items for a total maximum score of 24; higher values indicate more daytime sleepiness.
Time frame: 12 weeks
Population: Participants that completed the placebo controlled portion of the study (first 12 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early-start | Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the Epworth Sleepiness Scale (ESS). | 0 weeks (baseline) | 10.33 units on a scale | Standard Deviation 2.9 |
| Early-start | Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the Epworth Sleepiness Scale (ESS). | 12 weeks | 10.25 units on a scale | Standard Deviation 4.35 |
| Delayed-start | Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the Epworth Sleepiness Scale (ESS). | 0 weeks (baseline) | 9.00 units on a scale | Standard Deviation 4.58 |
| Delayed-start | Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the Epworth Sleepiness Scale (ESS). | 12 weeks | 8.71 units on a scale | Standard Deviation 2.69 |
Secondary
Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the REM Sleep Behavior Disorder Questionnaire (RBD-Q).
For each participant, the REM sleep behavior disorder questionnaire (RBD-Q) was self-administered by participants. The questionnaires were first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The RBD-Q score takes integer values between 0 and 1, for each of the 13 item yes/no questions for a total maximum score of 13; higher values indicate worse sleep behavior disorder.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early-start | Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the REM Sleep Behavior Disorder Questionnaire (RBD-Q). | 0 weeks (baseline) | 5.08 units on a scale | Standard Deviation 3.53 |
| Early-start | Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the REM Sleep Behavior Disorder Questionnaire (RBD-Q). | 12 weeks | 5.58 units on a scale | Standard Deviation 3.65 |
| Delayed-start | Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the REM Sleep Behavior Disorder Questionnaire (RBD-Q). | 0 weeks (baseline) | 5.42 units on a scale | Standard Deviation 2.37 |
| Delayed-start | Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the REM Sleep Behavior Disorder Questionnaire (RBD-Q). | 12 weeks | 3.57 units on a scale | Standard Deviation 2.37 |