Intensity of Aerobic Training and Neuroprotection in Parkinson's Disease

Parkinson's Disease Clinical Trial

— AEROPROTECT  

Official title:

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04046276
• Other study ID #: P140926
• Secondary ID: 2015-A01345-44
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2019
• Est. completion date: November 2021

Study information

• Verified date: August 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Jean-Michel GRACIES, MD, PhD
• Phone: +33 1 49 81 30 61
• Email: jean-michel.gracies[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

• To evaluate aerobic capacities before and after the program.

• To evaluate cognitive functions, depression, quality of life before and after each program as well as 3 months following program termination and motor function 3 months following program termination.

• To explore potential neuroprotective effects of a 9-month aerobic program through specialized brain imaging (123I-Ioflupane SPECT) and a potential aerobic intensity-effect of such neuroprotection.

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

• Two-minute walking test from D1 to M9

• Modified 20-meter up-and-go test (AT20)

• 2-minute walk test (from M1 to M12)

• Global Mobility Task (GMT) scale (standing up off the floor)

• Upper limb performance in activities of daily living (Mount Sinai Parkinsonism Impairment Rating Scale, MSPIR)

• Static posturography

• Maximal aerobic capacity (VO2 max)

• Montreal Cognitive Assessment test (MoCA)

• Digit span task (forward and backward)

• Trail Making Test

ON-state at D1, M9, M12

• MDS-UPDRS III Score;

• Mean number of steps performed over the past three weeks (pedometry);

• Monthly incidence of falls in the past 3 months (questionnaire)

• Daily consumption of dopaminergic medications

• Quality of life (EQ-5D)

• Depression (GDS15)

• Dopaminergic striatal function by SPECT [123I] beta-CIT striatal uptake at D1, M12.

Method Design

Single-blind randomized study, 3 parallel groups (n= 7 or 8 per group and per center, over 3 centers):

• Group 1 " High Intensity Aerobic exercise ", HIA (70% VO2 max);

• Group 2 " Medium Intensity Aerobic exercise ", MIA (50% VO2 max);

• Group 3 " Conventional Physical Therapy ", CPT HIA and MIA groups are experimental groups and CPT group is the control group. Each group will attend 3 weekly 45-minute sessions at the hospital for 9 months.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 69
• Est. completion date: November 2021
• Est. primary completion date: June 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of PD according to the UKPDSBB criteria

• 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

Exclusion 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 in the investigator's opinion

• 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.

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Behavioral:
• High Intensity Aerobic program
Three sessions a week of hospital-based exercise on a stationary bicycle, all in presence and with the guidance of a physical education teacher, for nine months

Other:
• Conventional Physical Therapy
Three sessions a week of hospital-based exercise on a stationary bicycle, all in presence and with the guidance of a physical education teacher, for nine months

Behavioral:
• Medium Intensity Aerobic program
Three sessions a week of hospital-based exercise on a stationary bicycle, all in presence and with the guidance of a physical education teacher, for nine months

Locations

Country	Name	City	State
France	Henri Mondor Hospital	Créteil
France	Sébastopol hospital	Reims
France	Rangueil hospital	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	The MDS-UPDRS III Score is a subjective assessment of motor symptoms based on the addition of ordinal 1-4 scores.	at day 1 and 9 Months
Secondary	Two-minute walking test at maximal speed		at day 1, 9 Months and 12 Months
Secondary	Modified 20-meter up-and-go test (AT20)		at day 1, 9 Months and 12 Months
Secondary	Global Mobility Task (GMT)	time required to stand up off the floor	at day 1, 9 Months and 12 Months
Secondary	Upper limb performance in activities of daily living (Mount Sinai Parkinsonism Impairment Rating Scale, MSPIR)	three unimanual tasks on each side and six bimanual everyday living tasks all times	at day 1, 9 Months and 12 Months
Secondary	Maximal aerobic capacity (VO2 max)		at day 1, 9 Months and 12 Months
Secondary	Montreal Cognitive Assessment test (MoCA)		at day 1, 9 Months and 12 Months
Secondary	Digit span task (forward and backward)		at day 1, 9 Months and 12 Months
Secondary	Trail Making Test		at day 1, 9 Months and 12 Months