Varenicline for Gait and Balance Impairment in Parkinson Disease
Varenicline for Gait and Balance Impairment in Parkinson Disease
The purpose of this study is to determine if varenicline is effective in improving gait and
 balance impairment in patients with Parkinson disease.
Parkinson disease (PD) is a clinical entity characterized by bradykinesia, rigidity, tremor,
 and postural instability. Current treatments primarily focus on replacement of dopamine to
 compensate for the degeneration of the substantia nigra pars compacta dopaminergic neuronal
 population. Though dopamine treats many of the motor symptoms of PD, postural instability
 (which often leads to falls) typically is least responsive to therapy. More recently, the
 degeneration of the cholinergic system arising from the pedunculopontine nucleus (PPN) in the
 brainstem has been implicated in gait dysfunction in PD. Striatal cholinergic inputs are
 supplied from the PPN both via the intralaminar complex of the thalamus and through direct
 inputs. The primary subtypes of cholinergic receptors present in the striatum are nicotinic
 and include α4β2, α6β2, and α7 receptors. Varenicline (Chantix) is a novel partial α4β2
 agonist and full α7 agonist developed as an aid for smoking cessation and has been shown in
 initial studies to improve imbalance in patients with inherited spinocerebellar ataxia. The
 unique method of action of varenicline may make it an ideal drug for the treatment of balance
 impairment in PD.
Inclusion Criteria:

 -  Subjects will be diagnosed with Parkinson Disease (PD) by the UK Brain Bank criteria.

 -  Subjects will have to be at least stage 2 on the Hoehn and Yahr staging system of PD
 and have a history of at least 1 fall or near fall in the last 6 months

 -  Subjects must have a stable medication regimen.

 -  All subjects will be over the age of 40 in an attempt to exclude inherited forms of
 parkinsonism.

 -  Serum creatine kinase, complete metabolic panel, complete blood count, liver function
 tests, renal function tests, platelets and EKG are within normal limits (results
 obtained from primary care physician and dated within the past 6 months or obtained at
 screening visit).

 Exclusion Criteria:

 -  Hoehn and Yahr stage V subjects.

 -  Subjects with a history of major psychiatric disorder, deep brain stimulation surgery,
 recent cerebral trauma, cardiac arrhythmia, or renal insufficiency.

 -  A cardiovascular procedure in the last 5 years (eg, percutaneous transluminal coronary
 angioplasty) or have cardiovascular instability (including myocardial infarction or
 unstable angina). Other cardiovascular exclusions include uncontrolled hypertension,
 significant neurological sequelae of cerebrovascular disease, peripheral vascular
 disease with prior amputation, or severe congestive heart failure (New York Heart
 Association class III or IV).

 -  Concurrent treatment with any MAOIs, bupropion (Wellbutrin), or nicotine patches.

 -  Dementia or other psychiatric illness that prevents the patient from giving informed
 consent (Folstein Mini Mental Status Exam score less than 25).

 -  Concurrent treatment with trihexyphenidyl (Artane) or benztropine mesylate (Cogentin).

 -  Significant degree of dysphagia, by history.

 -  Legal incapacity or limited legal capacity.

 -  Presence of severe renal disease (BUN 50% greater than normal or creatinine clearance
 <60 mL/min) or hepatic disease.

 -  Abnormal creatine kinase and/or platelet count in the past 6 months (as determined by
 lab reports obtained from primary care physicians or conducted at baseline).

 -  Use of varenicline within the previous 30 days.

 -  Women of childbearing potential who are pregnant at the time of screening or who will
 not use adequate protection during participation of the study.

 -  Allergy/sensitivity to the drug or its formulations.

 -  Concurrent participation in another clinical study.

 -  Active substance or tobacco use or dependence.

 -  Moderate or severe chronic obstructive pulmonary disease.

 -  Serious illness (requiring systemic treatment/or hospitalization) until the subject
 either completes therapy or is clinically stable on therapy, in the opinion of the
 site investigator, for at least 60 days prior to study entry.

 -  Inability or unwillingness of the subject or legal guardian/representative to give
 written informed consent.