Parkinson Disease Before and After Medication and Rehabilitation Treatment

The Role of Noradrenergic Network, and Its Association With Autonomous Dysfunction,Cerebral Autoregulation and microRNA in Parkinson Disease Before and After Medication and Rehabilitation Treatment

In this three-year project, our research teams are going to consecutively explore these important clinical, drug and physical rehabilitation treatment effects, noradrenergic network, autonomic dysfunction and microRNA signalling data as well as the correlations between them in early Parkinson Disease (PD) patients. The investigators hypothesize that the explorations of the above insights are unique and can provide an important source data for Taiwanese Parkinson Disease (PD).

Study Overview

• Status: Unknown
• Conditions: Parkinson Disease
• Intervention / Treatment: Behavioral: Rehabilitation treatment; Other: non-rehabilitation treatment

Detailed Description

(1) 70 patients with PD. (2) 30 age and sex-match controls.

Methods:

-1st year To built up the biobank of 30 early PD patients (Hoehn and Yahr stage 1-3) and 30 health controls in all examination.

The PD patients will accept the MRI, autonomic dysfunction, and peripheral microRNA examination and their correlations among each other at least 12 hours after the least medication.

-2nd year Second year, the investigators will follow-up the 30 PD patients enrolled in the 1st years.

The PD patients will receive studies to evaluate the pharmacokinetics effect before medication, including MRI, autonomic dysfunction, and peripheral microRNA examination.

-3rd year the investigators will study the rehabilitation effect in PD (3 days per week, for 12 weeks).

30 PD with rehabilitation and 30 PD without rehabilitation will be enrolled and compared their difference in MRI study, autonomic dysfunction, and peripheral microRNA examination before and after 3 month follow-up.

Goals

1. To define the effect of norepinephrine network to autonomic dysfunction in PD
2. To define the effect of peripheral microRNA level to norepinephrine network in PD
3. To associate drug/physical rehabilitation effect to alteration of norepinephrine network, autonomic dysfunction, and peripheral microRNA and their interactions to striatal dopaminergic network in PD.
4. According to previous results, to verify the role of norepinephrine network and autonomic dysfunction in long-term PD evolution.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• In this study, the patients should be 40-75 years of age and identified as PD. PD patients with an early clinical stage (Hoehn and Yahr stage 1-3) will be enrolled in this study. The informed written consent which is approved by Ethics Committee of our hospital will be obtained from the patient or their family.

Exclusion Criteria:

• Patients with the following conditions are excluded:

  1. Atherosclerotic narrowing on intracranial and extracranial vessels (>50% stenosis) with or without evidence of old cerebral infarctions, coronary artery diseases status post percutaneous transluminal coronary angioplasty or bypass surgery and renal failure requiring hemodialysis or peritoneal dialysis
  2. Moderate to severe heart failure (NYHA class III and IV).
  3. Central or peripheral disorders known to affect autonomic nervous systems.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Normal; 30 normal volunteers with age, sex and BMI-match as control group
Active Comparator: treatment group; The Rehabilitation treatment group will receive rehabilitation training once per day, 3 days per week, for 12 weeks. The duration of each session is about 1 hour. Participants will first receive relaxation exercises, positioning and self-stretch exercises (emphasizing on spinal mobility and flexor muscle groups of limbs and trunk) for 15 minutes. Then they will have balance training for 20 minutes. The investigators will use goal-directed tasks, such as different types of ball games, for balance training. At the end, participants will receive walking exercise for 20 minutes, and cool down exercises for 5 minutes.	Behavioral: Rehabilitation treatment; The walking exercise will be aerobic with a Borg rating perceived exertion around 11-14 scales. Before and after the 12 weeks rehabilitation training, should accept MRI and Clinical assessments.
Sham Comparator: non-treatment group; The group will not receive non-rehabilitation treatment, before and after the 12 weeks non-rehabilitation training, should accept MRI and Clinical assessments.	Other: non-rehabilitation treatment; The walking exercise will be aerobic with a Borg rating perceived exertion around 11-14 scales. Before and after the 12 weeks non-rehabilitation training, should accept MRI and Clinical assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuroimage	Conventional MRI, Rest function MRI Image Data Preprocessing, Assessment of cerebral blood flow with Arterial Spin Labeling (ASL) MRI and Chemical Exchange Saturation Transfer	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Rehabilitation_1	Unified Parkinson's Disease Rating Scale	12 weeks
Physical Rehabilitation_2	Walking speed by self-selected gait speed over 10 m	12 weeks
Physical Rehabilitation_3	Walking endurance, by using the 6-minute walk test	12 weeks
Physical Rehabilitation_4	Static and dynamic balance control, by using Biodex Balance System and Timed Up and Go test	12 weeks
Biochemical Analysis	interval change of serum MicroRNA level (increase of decrease)	18 months

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Study Director: Cheng-Hsien Lu, M.D., Chang Gung Memorial Hospital; Principal Investigator: Jen-Wen Hung, M.D., Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): August 1, 2016
• Study Completion (Anticipated): August 1, 2017

Study Registration Dates

• First Submitted: April 1, 2015
• First Submitted That Met QC Criteria: January 31, 2016
• First Posted (Estimate): February 3, 2016

Study Record Updates

• Last Update Posted (Estimate): February 3, 2016
• Last Update Submitted That Met QC Criteria: January 31, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Oxidative stress; Inflammation; Autonomic nervous system; Parkinson disease; MicroRNA; Rehabilitation treatment; noradrenergic network
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: NMRPG8D6031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO