Efficacy Study of Amantadine to Treat Gait Dysfunction and Freezing in Parkinson's Disease

Phase 3

Terminated

Conditions: Parkinson's Disease

Interventions: Drug: Placebo
Drug: Amantadine

Registration Number: NCT01652534

Lead Sponsor: Northwestern University

Brief Summary: The purpose of this study is to explore the efficacy of the drug Amantadine for the treatment of freezing of gait in patients with Parkinson's Disease. The investigators hypothesize that amantadine is useful for management of freezing of gait in subjects with Parkinson's Disease.

Detailed Description: Subjects who meet the eligibility requirements for the study will be randomized to Amantadine versus a matching placebo.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

Inclusion Criteria

Subjects with idiopathic PD as determined by UK brain bank diagnostic criteria
H&Y stage 2.5-3
Presence of freezing of gait (FOG) as determined by UPDRS Part I score > 2
Ability to walk for 2 minutes in the ON and OFF state
Stable regimen of PD medications for 30 days prior to screening
Ability to comply with the study procedures
If female, be either post menopausal for at least 2 years, surgically sterilized or have undergone hysterectomy or, if of child bearing potential they must be willing to avoid pregnancy by using an adequate method of contraception as defined in Section 6.4.10 for four weeks prior to, during and four weeks after the last dose of trial medication. For the purposes of this trial, women of childbearing potential are defined as all female subjects after puberty unless they are post-menopausal for at least two years, are surgically sterile or are sexually inactive.
Willing and able to provide informed consent.

Exclusion Criteria

Presence of other co morbid conditions that can contribute to gait dysfunction (orthopedic, rheumatologic, cardiac, other)
Presence of freezing of gait (FOG) ONLY in medications ON state
Presence of freezing of gait (FOG) ONLY in medications OFF state
Presence of significant cognitive dysfunction as determined by Montreal Cognitive Assessment (MoCA) <20
Presence of clinically significant depression as determined by geriatric depression scale (GDS)- 15>5
Presence of clinically significant hallucinations
Inability to sign informed consent
Participation in the physical therapy aimed at management of PD for the duration of the study (PT for orthopedic issues will be allowed)
Contraindications for use of Amantadine ( prior history of allergic reaction, history of known renal insufficiency with Cr > 2)
If female, be pregnant or lactating

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Sugar Pill
Amantadine	Amantadine	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day

Primary Outcome Measures

Name	Time	Method
Timed Up and Go (TUG) - ON Usual Medication	Baseline, change at 4 weeks	This is a walking assessment. The subject will begin in the seated position, stand up, walk 7 meters, turn around, and sit back down. The entire process from leaving the chair to returning to the chair will be timed. Also, the Timed Up and Go (TUG) will be done both in the ON and OFF states.
Timed Up and Go (TUG) - OFF Usual Medication	Baseline, change at 4 weeks	This is a walking assessment. The subject will begin in the seated position, stand up, walk 7 meters, turn around, and sit back down. The entire process from leaving the chair to returning to the chair will be timed. Also, the Timed Up and Go (TUG) will be done both in the ON and OFF states.

Secondary Outcome Measures

Name	Time	Method
Freezing of Gait Questionnaire	Baseline, change in 4 weeks	A questionnaire that is used to assess the likelihood of the subject freezing in a number of different scenarios. 0=No freezing of gait to 24=severe freezing of gait
Modified Timed Up and Go (mTUG)	Baseline, change in 4 weeks	The subject sits in the chair approximately 3 1/2 meters away from doorway with the door closed. Subject then stands up and walks one meter to a 40cm X 40cm box taped on the floor. Within the box the patient turns clockwise (360 degrees), then turns counterclockwise (360 degrees). Walk to open the door and walk through the doorway, turn around and return to the chair. Modified Timed Up and Go (mTUG) completed in three components including walking the course without additional tasks, carrying a tray with a cup of water, and counting backwards from 100, in both ON and OFF state.
Analysis of Motor Functioning Using the Parkinson's Home Diaries	Baseline, change in 4 weeks	Subject will record motor activity as OFF, ON (mobility improved) or asleep on the diary every half hour for two days. Subjects further define ON time according to dyskinesia categories "none", "non-troublesome" or "troublesome." The home diaries are used as an evaluation measure of the intervention by assessing the change in off time and change in on time with troublesome dyskinesia. The difference in time experiencing dyskinesia while ON meds relative to the time OFF meds at baseline and at 4 weeks is compared.
Clinical Global Impression (CGI)	4 weeks	Global Improvement is the second scale in the clinical global impression (CGI). Total overall improvement is judged by whether or not, in the judgment of the assessor, the improvement is entirely due to the drug treatment. It is also a 1-7 point weighted scale, going from "very much improved" (1) to "very much worse" (7). A zero score is assigned if the score is not assessed.
Parkinson's Disease Questionnaire-39 (PDQ-39)	Baseline, week 4	The Parkinson's Disease Questionnaire-39 (PDQ39) is a copyrighted instrument to assess symptoms of Parkinson's disease (PD) with 39 questions relating to mobility, activities of daily living, emotional well-being, social support, cognition, communication and bodily discomfort. The test asks subjects to rate each question regarding their Parkinson's disease symptoms over the past month. (range 0 to 100, lower scores reflect better quality of life)
Fatigue Severity Scale (FSS)	Baseline, change in 4 weeks	A questionnaire used to discriminate between Parkinson Disease (PD) patients with fatigue and those without fatigue. Range 9 to 63, higher scores indicate greater fatigue severity.
Gait Analysis Testing	Baseline, week 4, week 7, week 11	Use of an accelerometer such as Motorola Droid and wireless acceleration sensors to record gait parameters step time, walking speed, and cadence during the timed up and go (TUG) and modified timed up and go (mTUG) components. The sensors will be attached to the subject's legs and trunk using Velcro straps. The accelerometer will be held or clipped onto the subject in order to measure his or her acceleration. This is done within clinic and during the visit time.
Number Who Completed Medication as Randomized	week 4	Tolerability analysis as determined by the number of subjects completing each arm of the study.
Number of Participants With Drug Safety Reports	Week 4	Analyzing the safety of the medication, Amantadine. Data regarding the medication will be collected from the patient on each visit including any adverse events since the last visit, frequency and severity of falls. This is done in order to determine the safety of Amantadine.