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Modulation of Motor Function by Stimulation of the Central and Peripheral Nervous System

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier:
NCT00453505
First received: March 28, 2007
Last updated: November 11, 2014
Last verified: August 2014
  Purpose

Objectives

Noninvasive stimulation of the central and peripheral nervous system, including transcranial magnetic stimulation (TMS), theta-burst TMS (TBS), transcranial direct current stimulation (tDCS) and cutaneous/peripheral nerve stimulation (CPNS) alone or paired with TMS (paired associative stimulation, PAS), has been increasingly used in the investigation of cortical plasticity and as a possible adjuvant strategy in neurorehabilitation. It has been shown that TMS, TBS, tDCS and CPNS can successfully modulate motor function in healthy volunteers, as well as in patients with neurological disorders such as stroke.

One fundamental problem is that the optimal parameters of stimulation to modulate motor function by all of these techniques are not known. The purpose of this protocol is to explore within safe guidelines, the effects of different stimulation parameters on motor cortical function, on oscillatory brain dynamics measured with magnetoencephalography (MEG) and electroencephalography (EEG), on eye movements, and on fMRI activation. In addition, this protocol will be used to train new fellows coming to NINDS Human Cortical Physiology Section (HCPS) in the use of TMS, TBS, tDCS, and CPNS techniques.

We expect that information emerging from these studies will allow us to 1)optimize the stimulation parameters to collect pilot data in healthy volunteer for future patient-oriented hypothesis-driven protocols,2)to collect pilot data for power analysis for future patient-oriented hypothesis driven protocols, and 3) to train new fellows in the use of these different methods.

Study Population

Up to 1000 healthy volunteers, age 18 and older.

Design

Healthy volunteers will receive one or more of the following types of stimulation alone or in combination: (1) 1 Hz TMS for up to 30mins and up to 115% of resting motor threshold intensity (MT). These parameters are not being used for single-pulse TMS and paired-pulse TMS. Parameters for single-pulse TMS and paired-pulse TMS are variable as they depend on the sub-study. For paired pulses, duration of each TMS pulse is up to 1 msec. Interval between pulses is up to 20 sec and intensity of stimulation is up to 100 % of stimulator s output depending on the sub-study. (2) TBS below 100% active MT; (3) tDCS up to 2 mA for up to 60mins (4) CPNS with intensities below 130% of the peripherally-elicited-motor-threshold for up to 2 hours. All of these parameters of stimulation and procedures have safely been used as previously reported in the literature. Sham stimulations will be delivered for each modality.

Each subject may undergo up to 20 sessions spaced by at least one day, depending on the particular exploration. To verify that the number of sessions per subject does not exceed 20 sessions, the number of sessions per participant is tracked across substudies using CTDB. The AIs are responsible for entering into CTDB the subjects/visits. We will test the effects of these different forms of stimulation on motor cortical excitability, simple motor tasks, and functional neuroimaging measures. Some stimulation may be conducted before, after, or during fMRI scans, eye movement recording, MEG and/or EEG recording sessions. To identify the possible contribution of sub-cortical structures, we will also measure M-wave, F-wave, and/or H-Reflexes. The goal of these exploratory studies is to obtain preliminary information on the effects of these various combinations of central and peripheral nervous system stimulation that would allow us to develop subsequent, finely tuned, hypothesis-driven protocols.

Under this protocol, we conduct:

Exploratory Sub-studies. These substudies are exploratory in nature and are conducted in order to develop information to generate better informed hypotheses and/or power analyses. We have set an upper limit of 40 subjects per sub-study.

Hypothesis-Testing Sub-studies. Hypothesis-testing sub-studies are studies with specific hypotheses to be tested. These sub-studies undergo statistical and PIRC review after 6 subjects per group (e.g., after 12 subjects, 6 per arm, if two groups are studied), before additional subjects can be recruited. Together, the P.I. and PIRC will decide whether to continue the sub-study with more subjects without an amendment or whether an amendment or protocol would be necessary. A memo requesting a review of hypothesis-testing sub-studies for possible additional enrollment (beyond 6) will be sent to PIRC and the statistical reviewer.

In addition to the sub-study types above, this protocol is used to train new investigators and optimize various techniques and experimental approaches (e.g., appropriate MRI sequences, parameters of TMS stimulation, behavioral training duration).

We devised a strategy to ensure that a sub-study engages only procedures authorized in protocol and consent form and is scientifically valuable. F...


Condition
Healthy

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Modulation of Motor Function by Stimulation of the Central and Peripheral Nervous System

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 1000
Study Start Date: March 2007
  Hide Detailed Description

Detailed Description:

Objectives

Noninvasive stimulation of the central and peripheral nervous system, including transcranial magnetic stimulation (TMS), theta-burst TMS (TBS), transcranial direct current stimulation (tDCS) and cutaneous/peripheral nerve stimulation (CPNS) alone or paired with TMS (paired associative stimulation, PAS), has been increasingly used in the investigation of cortical plasticity and as a possible adjuvant strategy in neurorehabilitation. It has been shown that TMS, TBS, tDCS and CPNS can successfully modulate motor function in healthy volunteers, as well as in patients with neurological disorders such as stroke.

One fundamental problem is that the optimal parameters of stimulation to modulate motor function by all of these techniques are not known. The purpose of this protocol is to explore within safe guidelines, the effects of different stimulation parameters on motor cortical function, on oscillatory brain dynamics measured with magnetoencephalography (MEG) and electroencephalography (EEG), on eye movements, and on fMRI activation. In addition, this protocol will be used to train new fellows coming to NINDS Human Cortical Physiology Section (HCPS) in the use of TMS, TBS, tDCS, and CPNS techniques.

We expect that information emerging from these studies will allow us to 1)optimize the stimulation parameters to collect pilot data in healthy volunteer for future patient-oriented hypothesis-driven protocols,2)to collect pilot data for power analysis for future patient-oriented hypothesis driven protocols, and 3) to train new fellows in the use of these different methods.

Study Population

Up to 1000 healthy volunteers, age 18 and older.

Design

Healthy volunteers will receive one or more of the following types of stimulation alone or in combination: (1) 1 Hz TMS for up to 30mins and up to 115% of resting motor threshold intensity (MT). These parameters are not being used for single-pulse TMS and paired-pulse TMS. Parameters for single-pulse TMS and paired-pulse TMS are variable as they depend on the sub-study. For paired pulses, duration of each TMS pulse is up to 1 msec. Interval between pulses is up to 20 sec and intensity of stimulation is up to 100 % of stimulator s output depending on the sub-study. (2) TBS below 100% active MT; (3) tDCS up to 2 mA for up to 60mins (4) CPNS alone with intensities below 130% of the peripherally-elicited-motor-threshold for up to 2 hours. When CPNS is paired with TMS, the upper limit is up to 300% of the sensory threshold. All of these parameters of stimulation and procedures have safely been used as previously reported in the literature. Sham stimulations will be delivered for each modality.

Each subject may undergo up to 20 sessions spaced by at least one day, depending on the particular exploration. To verify that the number of sessions per subject does not exceed 20 sessions, the number of sessions per participant is tracked across substudies using CTDB. The AIs are responsible for entering into CTDB the subjects/visits. We will test the effects of these different forms of stimulation on motor cortical excitability, simple motor tasks, and functional neuroimaging measures. Some stimulation may be conducted before, after, or during fMRI scans, eye movement recording, MEG and/or EEG recording sessions. To identify the possible contribution of sub-cortical structures, we will also measure M-wave, F-wave, and/or H-Reflexes. The goal of these exploratory studies is to obtain preliminary information on the effects of these various combinations of central and peripheral nervous system stimulation that would allow us to develop subsequent, finely tuned, hypothesis-driven protocols.

Under this protocol, we conduct:

Exploratory Sub-studies. These substudies are exploratory in nature and are conducted in order to develop information to generate better informed hypotheses and/or power analyses. We have set an upper limit of 40 subjects per sub-study.

Hypothesis-Testing Sub-studies. Hypothesis-testing sub-studies are studies with specific hypotheses to be tested. These sub-studies undergo statistical and PIRC review after 6 subjects per group (e.g., after 12 subjects, 6 per arm, if two groups are studied), before additional subjects can be recruited. Together, the P.I. and PIRC will decide whether to continue the sub-study with more subjects without an amendment or whether an amendment or protocol would be necessary. A memo requesting a review of hypothesis-testing sub-studies for possible additional enrollment (beyond 6) will be sent to PIRC and the statistical reviewer.

In addition to the sub-study types above, this protocol is used to train new investigators and optimize various techniques and experimental approaches (e.g., appropriate MRI sequences, parameters of TMS stimulation, behavioral training duration).

We devised a strategy to ensure that a sub-study engages only procedures authorized in protocol and consent form and is scientifically valuable. First, the investigator submits the sub-study proposal to the PI which describes rationale, methods, techniques and/or behavioral tasks. The PI then meets with the investigator and the Protocol Coordinator (PC) to discuss the sub-study and make sure all procedures are allowed under protocol and consent form. Subsequently, the PI discusses at this time the pilot with the PIRC chair and suggestions are incorporated accordingly.

The status of each sub-study is reported to the IRB at the time of the continuing review.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Age 18 and older
    2. Willingness and ability to give consent
    3. Normal neurological examination
    4. Clearly dominant handedness (right or left) as assessed by Handedness scales

EXCLUSION CRITERIA:

  1. Any severe or progressive neurological disorder or severe medical condition, or history of seizures
  2. Chronic use of medications acting primarily on the central nervous system, which lower the seizure threshold or significantly alter cortical excitability such as antipsychotic drugs (chlorpromazine, clozapine), tricyclic or other antidepressants, or prescription stimulants.
  3. Pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments
  4. Diagnosis of drug dependence made by a health care provider (ICD-9-CM code 304)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00453505

Contacts
Contact: Rita Volochayev, C.R.N.P. (301) 402-0546 volochar@mail.nih.gov
Contact: Leonardo G Cohen, M.D. (301) 496-9782 cohenl1@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Leonardo G Cohen, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT00453505     History of Changes
Other Study ID Numbers: 070122, 07-N-0122
Study First Received: March 28, 2007
Last Updated: November 11, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Transcranial Direct Current Stimulation (TDCS)
Transcranial Magnetic Stimulation (TMS)
Peripheral Nerve Stimulation
Primary Motor Cortex
Corticomotor Excitability
Healthy Volunteer
HV

ClinicalTrials.gov processed this record on November 25, 2014