Investigating the Cholinergic Contribution to Gait Dysfunction in Parkinson's Disease
People with Parkinson's disease often experience problems with 'gait' and balance. Gait refers to the way a person moves while walking, such as their speed and length of steps. People with Parkinson's may experience slowness of movement, shuffle their feet, or have periods of 'freezing', during which their feet feel like they are stuck to the floor. Some people may struggle to maintain their balance and fall. These symptoms are frequently disabling and can lead to a worse quality of life. The nervous system is your body's messaging system - it helps different parts of your body communicate with one another. Neurotransmitters are chemicals that deliver those messages from one part of the body to another. The purpose of this study is to determine if the use of ARICEPT (Donepezil hydrochloride) improves gait and balance and its relation to the size of an area of the brain called Cholinergic Nucleus 4 (Ch4). The study team is also studying how degeneration (breakdown and eventual loss) in Ch4 contributes to problems with gait and balance. One way this may happen is through the loss of a chemical in the brain called acetylcholine. Acetylcholine is a neurotransmitter and its activity is associated with alertness, thinking, and the ability to move. Taking a drug that increases acetylcholine, such as ARICEPT, may improve gait and balance. By better understanding this relationship, we may be able to improve the treatment of gait and balance problems in the future.
⁃ Diagnosis of PD by a neurologist as per UK Brain Bank criteria
⁃ Age 40 or older
⁃ Clinical evidence of gait dysfunction, as determined by a movement disorders neurologist.
⁃ Willingness and ability to comply with scheduled visits and study procedures.
⁃ Actively treated with a stable dose of levodopa or other anti-parkinsonian medications.
⁃ Able to ambulate without the use of an assistive device.
⁃ Serum chemistry from blood obtained at screening will need to be free from evidence of renal injury (elevated creatinine) or other significant metabolic abnormalities at the discretion of the examiner within 28 days of study initiation.
⁃ Subject agrees not to participate in another study with an investigational drug/treatment during this study and for 3 months following study completion.
⁃ Female subjects must not be breastfeeding and must have a negative serum pregnancy test at Visit 1. Women of childbearing potential (WOCBP) must use one of the following acceptable birth control methods as specified before enrollment and throughout the trial:
∙ Surgical sterilization (bilateral tubal occlusion/ligation) prior to signing the informed consent form (ICF).
‣ Intrauterine device in place for at least 3 months before the first dose of study drug and throughout the trial.
‣ Barrier method (condom or diaphragm) with spermicide for at least 30 days before the first dose of the study drug and throughout the trial.
‣ Surgical sterilization of the male partner (vasectomy at least 6 months before the first dose of study drug).
‣ Hormonal contraceptives with a barrier method for at least 3 months before the first dose of the study drug and throughout the trial.
• Female subjects are not considered to be of childbearing potential if they meet at least one of the following criteria as documented by the Investigator:
• They have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at minimum one menstrual cycle prior to signing the ICF.
• They are postmenopausal, defined as 1 year since the last menstrual period without an alternative medical cause or have a follicle-stimulating hormone (FSH) level in the menopausal range (defined as \>20 miU/mL and \<122 miU/mL) in women who are not using hormonal contraception or hormonal replacement therapy and are ≥50 years of age.
• For women ≤50 years old, ≥2 years since her last menstrual period without an alternative.