Modafinil for Freezing of Gait (FOG) in Parkinson's Disease (PD)

Phase 2

Completed

Conditions: Parkinson Disease

Interventions: Drug: modafinil 50mg
Drug: Placebo oral capsule

Registration Number: NCT03083132

Lead Sponsor: University of Arkansas

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early-start	modafinil 50mg	24 weeks of modafinil 50 mg oral daily
Delayed-start	modafinil 50mg	12 weeks of oral placebo followed by 12 weeks of modafinil 50 mg oral daily
Delayed-start	Placebo oral capsule	12 weeks of oral placebo followed by 12 weeks of modafinil 50 mg oral daily

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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 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.