Study in Parkinson Disease of Exercise
Study in Parkinson Disease of Exercise
This study is a Phase 3 multi-site, randomized, evaluator-masked, study of endurance
 treadmill exercise on changes in the Movement Disorder Society-Unified Parkinson Disease
 Rating Scale (MDS-UPDRS) Part III score at 12 months among persons with early stage Parkinson
 disease. 370 participants will be randomly assigned to 2 groups: 1)60-65% HRmax or 2)80-85%
 HRmax 4 times per week. The primary objective is to test whether the progression of the signs
 of Parkinson's disease is attenuated at 12 months in among persons who have not initiated
 medication for Parkinson Disease (PD) when they perform high-intensity endurance treadmill
 exercise.
This study is a Phase 3 multi-site, randomized, evaluator-masked, study of endurance
 treadmill exercise on changes in the MDS-UPDRS Part III score at 12 months. 370 persons
 diagnosed with Parkinson's disease who have not yet initiated dopaminergic therapy, age
 40-80, will be randomly assigned to 2 groups: 1)60-65% HRmax or 2)80-85% HRmax 4 times per
 week. Secondary objectives will test hypotheses related to striatal specific binding ratio
 (SSBR) at 12 months, MDS-UPDRS Part III score, ambulatory mobility (6-minute walk), daily
 walking activity (steps), cognition, quality of life, cardiorespiratory fitness,
 blood-derived biomarkers of inflammation and neurotrophic factors at 12 and 18 months.
 Tertiary objectives will test hypotheses related to 2 characteristics of ambulation at 12 and
 18 months. Exploratory objectives will test hypotheses related to the effects of removing the
 study support that was provided over 18 months on the sustainability and durability of the
 exercise effects at 24 months. Approximately 29 sites will enroll participants: 27 sites that
 cover all geographic regions of the USA and 2 sites in Canada. All sites will have a
 collaboration between movement disorders and exercise specialists.
Inclusion Criteria:

 -  A diagnosis of idiopathic Parkinson Disease based on the modified * United Kingdom
 (UK) PD brain bank criteria and which are consistent with recent criteria proposed for
 clinically established early established Parkinson's disease that no longer exclude
 individuals with a family history of Parkinson's disease.

 -  Hoehn and Yahr stages less than 3

 -  Disease duration: less than 3 years since disease diagnosis

 -  Age 40-80 years

 -  Positive DaTscan™ SPECT by quantitative readout for idiopathic Parkinson disease.

 Exclusion Criteria:

 -  Currently being treated with PD medications such as levodopa or dopamine receptor
 agonists, monoamine oxidase-B (MAO-B) inhibitors, amantadine, or anticholinergics.

 -  Expected to require treatment with medication for PD in the first 6 months of the
 study.

 -  Use of any PD medication 60 days prior to the baseline visit including but not limited
 to levodopa, direct dopamine agonists, amantadine, Rasagiline (Azilect), Selegiline
 (Eldepryl), Artane (trihexyphenidyl).

 -  Duration of previous use of medications for PD exceeds 30 days.

 -  Use of neuroleptics/dopamine receptor blockers for more than 30 days in the year prior
 to baseline visit, or any use within 30 days of baseline visit

 -  Presence of known cardiovascular, metabolic, or renal disease or individuals with
 major signs or symptoms suggestive of cardiovascular, metabolic, or renal disease
 without medical clearance to participate in the exercise program.

 -  Uncontrolled hypertension (resting blood pressure >150/90 mmHg)

 -  Individuals with orthostatic hypotension and standing systolic BP below 100 will be
 excluded. Orthostatic hypotension (OH) is a reduction of systolic blood pressure of at
 least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within 3 minutes of
 standing.

 -  Hypo- or hyperthyroidism (TSH <0.5 or >5.0 mU/L), abnormal liver function (AST or ALT
 more than 2 times the upper limit of normal), abnormal renal function (creatinine
 clearance calculated by the Cockcroft-Gault equation <50mL/min, or estimated
 glomerular filtration rate using the MDRD4 equation or the CKD-EPI equation
 <45mL/min/1.73m2 ).

 -  Complete Blood Count (CBC) out of range and physician's judgment that abnormal value
 is clinically significant.

 -  Recent use of psychotropic medications (e.g., anxiolytics, hypnotics, benzodiazepines,
 antidepressants) where dosage has not been stable for 28 days prior to screening.

 -  Serious illness (requiring systemic treatment and/or hospitalization) within the last
 4 weeks.

 -  Any other clinically significant medical condition, psychiatric condition, drug or
 alcohol abuse, assessment or laboratory abnormality that would, in the judgment of the
 investigator, interfere with the subject's ability to participate in the study.

 -  Montreal Cognitive Assessment (MoCA) score of <26 to rule out mild cognitive
 impairment (MCI).

 -  Beck Depression Inventory II (BDI) score > 16, indicating depression that precludes
 ability to exercise. Any subject with such a score will be referred to a primary care
 physician (PCP) or physician for further evaluation and management of depression.

 -  Individuals participating in 120 minutes or more of moderate intensity exercise per
 week within the last 6 months will be excluded. Moderate intensity is defined as a
 range greater than 60-65% HRmax. These individuals are excluded since their exercise
 activities are equal to or greater than the activities they would experience if they
 were assigned to the 60-65% treatment group.

 -  Use of the following within 90 days prior to the dopamine transporter (DAT)
 neuroimaging screening evaluation: bupropion, modafinil, armodafinil, metoclopramide,
 alpha-methyldopa, methylphenidate, reserpine, any amphetamine or amphetamine
 derivative. These can compromise DaTscan™ SPECT.

 -  Known allergy to iodinated products.

 -  Known hypersensitivity to DaTscan™ SPECT (either to the active substance of
 123I-ioflupane or any of the excipients.

 -  Prior SPECT scan within 6 months of baseline scan. Recruitment will be delayed for
 individuals who have had a previous SPECT scan within 6 months of the baseline scan.

 -  (For women only) Actively breast-feeding an infant, and/or pregnant, or plan to become
 pregnant in the next 12 months.

 -  Other disorders, injuries, diseases, or conditions that might interfere with ability
 to perform endurance exercises (e.g. history of stroke, respiratory problems,
 traumatic brain injury, orthopedic injury, or neuromuscular disease).