Study in Parkinson Disease of Exercise Phase 3 Clinical Trial: SPARX3

– 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)

– 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, 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.

– “Vigorous athletes” participating in any endurance exercise program 3x/week or more
will be excluded. Vigorous is defined as endurance exercise in a range greater than
60-65% HRmax. These individuals are excluded since their exercise activities are
similar to 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) 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).