Exercise and Transcranial Magnetic Stimulation: Increasing Brain Plasticity in Parkinson's Disease

This is a feasibility and exploratory study consisting of two parts: first, a cross-sectional (one-time) biomarker measurement comparing BDNF-TrkB (Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB,) signaling and cortical plasticity in patients diagnosed with Parkinson's Disease (PD) vs. healthy controls matched by age. Second, a prospective, randomized, double blind trial of Transcranial Magnetic Stimulation (TMS) MAGSTIM Rapid2 Therapy System (TMS) (real or Sham) and aerobic exercise. This exploratory feasibility study will look at BDNF-TrkB signaling and cortical plasticity.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Behavioral: Sham rTMS; Behavioral: Supervised aerobic exercise; Other: Real rTMS

Detailed Description

Twenty-four PD patients (n=24) will be randomly assigned to receive one of two interventions for a duration of two weeks. In Group 1, subjects will participate in daily sessions of sham-rTMS followed by supervised aerobic exercise (Sham rTMS+Aerobic); in Group 2, subjects will participate in a combination of rTMS and supervised aerobic exercise (Real rTMS+Aerobic). Serum BDNF-TrkB signaling in lymphocytes and TMS-based electrophysiological measures of LTP-like plasticity will be measured. A comparison of such measures in a group of patients with PD and in a group of age-matched controls (n=12) will be analyzed to establish the effect of the disease on indices of plasticity.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of PD according to the UK Brain Bank Criteria, confirmed by a neurologist with expertise in movement disorders;
• Hoehn and Yahr stage II to III;
• On a stable medication regimen since at least 2 weeks prior the enrolment in the study and, in the view of the treating neurologist, unlikely to require medication adjustments in the following 3-6 months.

Inclusion Criteria (Healthy Controls)

• Male or Female; aged 35-85

Exclusion Criteria (Healthy Controls)

• History of seizure disorder, including febrile seizures;
• Neurological disorder including PD, stroke, traumatic brain injury, fainting spells or syncope of unknown cause(s);
• Major or unstable medical illness;
• Pacemakers, neurostimulators, tattoos or metal foreign bodies in the head area (dental fillings are allowed);
• Untreated depression, or score of >20 on Beck Depression Inventory II;
• Taking any of the following medications within the six weeks prior to the start of the study: imipramine, amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, theophylline, calcium channel blockers, beta blockers, tadalafil, vardenafil, avanafil, and sildenafil;
• Diagnosis of dementia, or Montreal Cognitive Assessment (MoCA) <20;
• Any clinically significant abnormality on vital signs
• Cardiopulmonary limitations: untreated high blood pressure, history of heart insufficiency (class II-III), coronary vascular disease, angina, arrhythmia, dyspnea on exertion and asthma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: Sham Group; Sham group will receive Sham rTMS+Aerobic Exercise	Behavioral: Sham rTMS; Subjects will participate in daily sessions of sham-rTMS; Behavioral: Supervised aerobic exercise
Experimental: Group 2: Real Group; rTMS+Aerobic Exercise	Behavioral: Supervised aerobic exercise; Other: Real rTMS; Subjects will participate in a combination of rTMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recruitment Enrollment Numbers	2 Weeks
Number of enrolled subjects that remain in study	2 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasticity measured by TMS-PAS25 (LTP-like plasticity biomarker)	A paired associative paradigm at 25 ms (TMS-PAS-25) to quantify cortical LTP in M1 motor cortex will be used. As well as a repetitive biphasic magnetic stimulator (Magstim Rapid2 stimulator -Magstim Co., Whitland, U.K.) with a "Figure of eight" coil (outer diameters: 9 cm) and apply standard protocol for LTP-like measurements.	2 Weeks
Measurements of lymphocytes		2 Weeks
Measurements of TrkB		2 Weeks
Measurements of serum BDNF		2 Weeks
Timed Up and Go Test		2 Weeks
Freezing of Gait Questionnaire (FOG-Q)		2 Weeks
Parkinson's Disease Quality of Life (PDQ-39)		2 Weeks
Parkinson's Disease Sleep Scale (PDSS)		2 Weeks
Frontal Function Assessment (FAB)		2 Weeks
LASA Physical Activity Questionnaire (LAPAQ)		2 Weeks

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Milton Biagioni, MD, New York University Medical School

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): January 26, 2018
• Study Completion (Actual): January 26, 2018

Study Registration Dates

• First Submitted: March 31, 2016
• First Submitted That Met QC Criteria: April 13, 2016
• First Posted (Estimate): April 18, 2016

Study Record Updates

• Last Update Posted (Actual): July 16, 2019
• Last Update Submitted That Met QC Criteria: July 12, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Exercise; Transcranial Magnetic Stimulation; Brain Plasticity
• 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: 15-00712

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No