Neuroprotective, Motor and Cognitive Impact of a Long-standing Aerobic Training Program in Parkinson's Disease. A Multicenter Comparison of the Effects of Two Aerobic Programs of Graded Intensities and a Conventional Physical Therapy Program Prolonged for 9 Months on Nigrostriatal, Motor and Cognitive Functions.
Neuroprotective, Motor and Cognitive Impact of a Long-standing Aerobic Training Program in Parkinson's Disease. A Multicenter Comparison of the Effects of Two Aerobic Programs of Graded Intensities and a Conventional Physical Therapy Program Prolonged for 9 Months on Nigrostriatal, Motor and Cognitive Functions.
In phenotypic animal models of Parkinson's Disease (PD), chronic physical exercise has produced nigrostriatal neuroprotection and symptom improvement, provided training was of high-intensity and prolonged duration (>3 months in rodent models). Conventional physical therapy in Parkinson's disease (PD) has traditionally avoided fatigue and high intensity workouts. Yet, in PD controlled studies have shown that: (i) an acute aerobic stress produces endogenous dopamine immediately after the exercise and (ii) short term (a few weeks) high intensity aerobic training enhances D2 striatal receptor density and cortical excitability and clinically improves walking, upper limb and executive functions; (iii) long-term (six months) high intensity aerobic treadmill training is associated with less deterioration of subjective UPDRS III score compared to a waiting list. Long-term high intensity aerobic training has not been compared to low or medium intensity training in PD patients for its objective motor, cognitive and putative neuroprotective effects.
A short description, 5000 characters Intro: In phenotypic animal models of Parkinson's Disease (PD), chronic physical exercise has produced nigrostriatal neuroprotection and symptom improvement, provided training was of high-intensity and prolonged duration (>3 months in rodent models). Conventional physical therapy in Parkinson's disease (PD) has traditionally avoided fatigue and high intensity workouts. Yet, in PD controlled studies have shown that: (i) an acute aerobic stress produces endogenous dopamine immediately after the exercise and (ii) short term (a few weeks) high intensity aerobic training enhances D2 striatal receptor density and cortical excitability and clinically improves walking, upper limb and executive functions; (iii) long-term (six months) high intensity aerobic treadmill training is associated with less deterioration of subjective UPDRS III score compared to a waiting list. Long-term high intensity aerobic training has not been compared to low or medium intensity training in PD patients for its objective motor, cognitive and putative neuroprotective effects.
Hypothesis/Objective
Hypothesis High-intensity aerobic exercises practiced over 9 months will produce greater symptomatic motor and cognitive benefits and neuroprotective effects in PD patients, than low or medium intensity training.
Primary Objective To compare the motor effects of a 9-month conventional physical therapy program (light aerobic exercises), an aerobic program of medium intensity on stationary bicycle (50% maximal oxygen uptake, VO2 max), and an aerobic program of high intensity (70% VO2 max) in Parkinson's disease.
Secondary Objectives
Primary outcome measure Change in MDS-UPDRS III Score (Movement Disorders Society - Unified Parkinson's Disease Rating Scale) in the " OFF " state between Day 1 and Month 9.
Secondary outcome measures OFF-state at Day 1, Month 9, Month 12
ON-state at D1, M9, M12
Method Design
Single-blind randomized study, 3 parallel groups (n= 7 or 8 per group and per center, over 3 centers):
Number of subjects needed: 69 Inclusion criteria Patients with diagnosis of PD according to the UKPDSBB criteria to distinguish idiopathic PD from atypical parkinsonism such as multi-system atrophy, progressive supra-nuclear paralysis or vascular parkinsonism; Previous MRI available, to further help distinguish idiopathic PD from atypical parkinsonism; Hoehn & Yahr Stage 1-3 in OFF state; Age > 18; Signed informed consent to participate in study.
Non-inclusion criteria Patients lacking motivation or ability to participate in training sessions for 9 months, in the investigator's opinion; contra-indications to high-intensity aerobic training in the cardiologist's opinion; contra-indications to perchlorate de potassium or to the use of 123I-FP-CIT; concurrent severe co-morbidities; cognitive deficit limiting participation to the program; Montreal Cognitive Assessment test (MoCA)<23; uninsured patient; participation in another ongoing interventional clinical trial (drug therapy, surgical treatment, another rehabilitation treatment, medical device); Pregnancy or current lactation, or no efficacious contraception during the 9 months of intervention.
Recruitment period: 1 year; Study duration: 26 months (24 patients recruited in 2 centers and 21 patients in the other 2 centers) Participation duration for each patient: 14 months Number of participating centers: 3
Inclusion Criteria:
Exclusion Criteria:
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