MetaplasticityNCT00331318
Improving Hand Movement Training Through Electrical Stimulation of the Brain
An observational study of Metaplasticity, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will determine if applying electrical stimulation of the brain can influence training to perform finger movements. The study may provide information that can be used to design rehabilitation therapies for people who have lost the ability to move a part of their body, such as an arm, leg, or hand following a… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Metaplasticity
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 24 May 2006to 21 Apr 2008
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- age between 18-50 years
- able to perform tasks required by the study
- willing and able to give consent
- willing to make an eight-week commitment to the study
- possibility of obtaining TMS-evoked thumb movements in a consistent direction at baseline
Who cannot join
- unable to perform the tasks
- history of severe alcohol or drug abuse, psychiatric illness such as severe depression, poor motivational capacity, or severe language disturbances, particularly of receptive nature or with serious cognitive deficits (defined as equivalent to a mini-mental state exam score (MMSE) of 23 or less), or degenerative brain processes such as Alzheimer's disease
- severe uncontrolled medical problems (e.g., cardiovascular disease, severe rheumatoid arthritis, active joint deformity of arthritic origin, active cancer or renal disease, any kind of end-stage pulmonary or cardiovascular disease, or a deteriorated condition due to age, uncontrolled epilepsy or others), more than moderate to severe microangiopathy, polyneuropathy, diabetes mellitus, or ischemic peripheral disease
- problems with movement of the hands
- receiving drugs acting primarily on the central nervous system, which lower the seizure threshold such as antipsychotic drugs (chlorpromazine, clozapine) or tricyclic antidepressants (for the TMS component)
- pregnancy and during lactation
- medical or technical contraindications to MRI procedures or devices producing artifacts that impair MRI signal (e.g., dental braces, pacemakers, implanted medication pumps, cochlear devices, neural stimulators, metal in the cranium, surgical clips, and other metal/magnetic implants, claustrophobia)
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Encoding a Motor Memory Through Metaplasticity
This study will determine if applying electrical stimulation of the brain can influence training to perform finger movements. The study may provide information that can be used to design rehabilitation therapies for people who have lost the ability to move a part of their body, such as an arm, leg, or hand following a stroke.
Healthy volunteers 18-50 years of age may be eligible for this study. Candidates are screened with a medical history, physical examination, MRI (if one has not been done within the last year), questionnaire to evaluate memory and attention and a pregnancy test for women who can become pregnant.
Read more
Participants have the following tests and procedures in seven sessions over about 8 weeks:
- Questionnaires to test attention, fatigue and mood before, during and after each session
- Surface electromyography: Electrodes are filed with a conductive gel and taped to the skin over one small hand muscle to measure the electrical activity of muscles.
- Transcranial magnetic stimulation: A wire coil is held on the scalp. A brief electrical current passes through the coil to stimulate the brain. During the stimulation, the subject may be asked to tense certain muscles slightly or perform other simple actions. The stimulation may cause a twitch in muscles of the face, arm, or leg, and the subject may hear a click and feel a pulling sensation on the skin under the coil.
- Transcranial direct stimulation (tDCS) before and during motor training: Small, wet sponge electrodes are applied to the head - one above the eye and the other on the back of the head. A small electrical current is passed between them. The subject may feel an itching or tingling sensation under the electrodes or see light flashes.
- Motor learning under tDCS: tDCS is repeated while the subject performs the training task. The training task consists of performing voluntary brisk thumb movements in a direction opposite to TMS-induced movement directions, during 30 minutes. Training blocks are in 10-minute segments and tDCS is applied during the first 20 minutes.
- Behavioral measurements: Evaluation of learned movement tasks.
Read the detailed description
OBJECTIVES:
Training leads to performance improvements and motor learning. Cortical plasticity associated with training (use-dependent plasticity, UDP) contributes to performance improvements after brain lesions such as stroke. Recently, several interventional strategies have been proposed to enhance UDP, including pharmacological approaches and brain stimulation. The magnitude of improvements identified with these techniques is limited. It would be very useful to enhance UDP beyond the limited effects of previously proposed interventions.
One strategy recently proposed to enhance the effect of brain stimulation techniques on the cerebral cortex is metaplasticity. This strategy focuses on the purposeful manipulation of cortical activity before applying brain stimulation. For example, previous work demonstrated that the magnitude of increase in cortical excitability elicited by stimulation of the primary motor cortex (M1) is more prominent if stimulation is applied on a hypoactive M1. An initial down-regulation of M1 activity (i) amplifies the effect of a subsequent intervention that increases M1 activity, and (ii) reduces inter-individual variability.
It is unknown if this metaplasticity strategy can enhance the beneficial effects of anodal tDCS (tDCS anodal) on training effects as it does with cortical excitability, an issue of scientific and clinical interest, and the overall hypothesis of this protocol.
Here, we will test the hypothesis that metaplasticity (tDCS cathodal) followed by tDCS anodal plus motor training will result in more prominent UDP than control interventions.
STUDY POPULATION
6 healthy adult volunteers for parameters estimation plus 25 healthy adult volunteers (total = 31 healthy adult volunteers)
DESIGN
In this protocol, down-regulation of M1 activity will be accomplished by applying tDCS cathodal, a tool extensively described in the literature to induce this effect. Therefore, we will test the effects of this metaplasticity intervention on the beneficial action of tDCS anodal to M1 in combination with motor training (MT). After a familiarization session, subjects will participate in 6 randomized sessions in a cross-over design:
- Preconditioning tDCS cathodal followed by Intervention tDCS anodal plus MT Purpose Target metaplasticity condition
- Preconditioning Sham followed by Intervention Sham plus MT Purpose Effects of motor training alone
- Preconditioning Sham followed by Intervention tDCS anodal plus MT Purpose Mild improvement in training effects
- Preconditioning tDCS cathodal followed by Intervention Sham plus MT Purpose Effects of tDCS cathodal alone on MT
- Preconditioning tDCS anodal followed by Intervention Sham plus MT Purpose Effects of polarity on tDCS effects
- Preconditioning tDCS anodal followed by Intervention tDCS anodal plus MT Purpose Control for the metaplasticity condition
MT will consist of brisk repetitive thumb movements in a direction opposite to the baseline direction of thumb movements evoked by focal transcranial magnetic stimulation (TMS), in a well-characterized UDP protocol.
The primary outcome measure reflecting the encoding of a motor memory will be the increased proportion of TMS-evoked movements falling within the target training zone (TTZ) as a function of MT and metaplasticity interventions.
- Conditions
- Metaplasticity
- Keywords
- Transcranial Direct Current Stimulation (tDCS), Transcranial Magnetic Stimulation (TMS), Motor Learning, Brain Plasticity, Healthy Volunteer, HV
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2006 (estimated)
- Study start24 May 2006
- Study completion21 Apr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MetaplasticityStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 31 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00331318
- Sponsor's protocol ID
- 060171
- Other IDs
- 06-N-0171
- Status last verified
- 21 Apr 2008
- First submitted
- 27 May 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Siebner HR, Lang N, Rizzo V, Nitsche MA, Paulus W, Lemon RN, Rothwell JC. Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex. J Neurosci. 2004 Mar 31;24(13):3379-85. doi: 10.1523/JNEUROSCI.5316-03.2004.
PubMed 15056717
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Encoding a Motor Memory Through Metaplasticity
- ClinicalTrials.gov ID
- NCT00331318
- Acronym / sponsor ID
- 060171
- Conditions
- Metaplasticity
- Keywords
- Transcranial Direct Current Stimulation (tDCS), Transcranial Magnetic Stimulation (TMS), Motor Learning, Brain Plasticity, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 31 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 24 May 2006
- Study completion
- 21 Apr 2008
- First posted
- 29 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine if applying electrical stimulation of the brain can influence training to perform finger movements. The study may provide information that can be used to design rehabilitation therapies for people who have lost the ability to move a part of their body, such as an arm, leg, or hand following a stroke.
Healthy volunteers 18-50 years of age may be eligible for this study. Candidates are screened with a medical history, physical examination, MRI (if one has not been done within the last year), questionnaire to evaluate memory and attention and a pregnancy test for women who can become pregnant.
Participants have the following tests and procedures in seven sessions over about 8 weeks:
- Questionnaires to test attention, fatigue and mood before, during and after each session
- Surface electromyography: Electrodes are filed with a conductive gel and taped to the skin over one small hand muscle to measure the electrical activity of muscles.
- Transcranial magnetic stimulation: A wire coil is held on the scalp. A brief electrical current passes through the coil to stimulate the brain. During the stimulation, the subject may be asked to tense certain muscles slightly or perform other simple actions. The stimulation may cause a twitch in muscles of the face, arm, or leg, and the subject may hear a click and feel a pulling sensation on the skin under the coil.
- Transcranial direct stimulation (tDCS) before and during motor training: Small, wet sponge electrodes are applied to the head - one above the eye and the other on the back of the head. A small electrical current is passed between them. The subject may feel an itching or tingling sensation under the electrodes or see light flashes.
- Motor learning under tDCS: tDCS is repeated while the subject performs the training task. The training task consists of performing voluntary brisk thumb movements in a direction opposite to TMS-induced movement directions, during 30 minutes. Training blocks are in 10-minute segments and tDCS is applied during the first 20 minutes.
- Behavioral measurements: Evaluation of learned movement tasks.
Detailed description
OBJECTIVES:
Training leads to performance improvements and motor learning. Cortical plasticity associated with training (use-dependent plasticity, UDP) contributes to performance improvements after brain lesions such as stroke. Recently, several interventional strategies have been proposed to enhance UDP, including pharmacological approaches and brain stimulation. The magnitude of improvements identified with these techniques is limited. It would be very useful to enhance UDP beyond the limited effects of previously proposed interventions.
One strategy recently proposed to enhance the effect of brain stimulation techniques on the cerebral cortex is metaplasticity. This strategy focuses on the purposeful manipulation of cortical activity before applying brain stimulation. For example, previous work demonstrated that the magnitude of increase in cortical excitability elicited by stimulation of the primary motor cortex (M1) is more prominent if stimulation is applied on a hypoactive M1. An initial down-regulation of M1 activity (i) amplifies the effect of a subsequent intervention that increases M1 activity, and (ii) reduces inter-individual variability.
It is unknown if this metaplasticity strategy can enhance the beneficial effects of anodal tDCS (tDCS anodal) on training effects as it does with cortical excitability, an issue of scientific and clinical interest, and the overall hypothesis of this protocol.
Here, we will test the hypothesis that metaplasticity (tDCS cathodal) followed by tDCS anodal plus motor training will result in more prominent UDP than control interventions.
STUDY POPULATION
6 healthy adult volunteers for parameters estimation plus 25 healthy adult volunteers (total = 31 healthy adult volunteers)
DESIGN
In this protocol, down-regulation of M1 activity will be accomplished by applying tDCS cathodal, a tool extensively described in the literature to induce this effect. Therefore, we will test the effects of this metaplasticity intervention on the beneficial action of tDCS anodal to M1 in combination with motor training (MT). After a familiarization session, subjects will participate in 6 randomized sessions in a cross-over design:
- Preconditioning tDCS cathodal followed by Intervention tDCS anodal plus MT Purpose Target metaplasticity condition
- Preconditioning Sham followed by Intervention Sham plus MT Purpose Effects of motor training alone
- Preconditioning Sham followed by Intervention tDCS anodal plus MT Purpose Mild improvement in training effects
- Preconditioning tDCS cathodal followed by Intervention Sham plus MT Purpose Effects of tDCS cathodal alone on MT
- Preconditioning tDCS anodal followed by Intervention Sham plus MT Purpose Effects of polarity on tDCS effects
- Preconditioning tDCS anodal followed by Intervention tDCS anodal plus MT Purpose Control for the metaplasticity condition
MT will consist of brisk repetitive thumb movements in a direction opposite to the baseline direction of thumb movements evoked by focal transcranial magnetic stimulation (TMS), in a well-characterized UDP protocol.
The primary outcome measure reflecting the encoding of a motor memory will be the increased proportion of TMS-evoked movements falling within the target training zone (TTZ) as a function of MT and metaplasticity interventions.
Study design
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- age between 18-50 years
- able to perform tasks required by the study
- willing and able to give consent
- willing to make an eight-week commitment to the study
- possibility of obtaining TMS-evoked thumb movements in a consistent direction at baseline
Key exclusion criteria (7 listed)
- unable to perform the tasks
- history of severe alcohol or drug abuse, psychiatric illness such as severe depression, poor motivational capacity, or severe language disturbances, particularly of receptive nature or with serious cognitive deficits (defined as equivalent to a mini-mental state exam score (MMSE) of 23 or less), or degenerative brain processes such as Alzheimer's disease
- severe uncontrolled medical problems (e.g., cardiovascular disease, severe rheumatoid arthritis, active joint deformity of arthritic origin, active cancer or renal disease, any kind of end-stage pulmonary or cardiovascular disease, or a deteriorated condition due to age, uncontrolled epilepsy or others), more than moderate to severe microangiopathy, polyneuropathy, diabetes mellitus, or ischemic peripheral disease
- problems with movement of the hands
- receiving drugs acting primarily on the central nervous system, which lower the seizure threshold such as antipsychotic drugs (chlorpromazine, clozapine) or tricyclic antidepressants (for the TMS component)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 15056717Siebner HR, Lang N, Rizzo V, Nitsche MA, Paulus W, Lemon RN, Rothwell JC. Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex. J Neurosci. 2004 Mar 31;24(13):3379-85. doi: 10.1523/JNEUROSCI.5316-03.2004.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metaplasticity, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00331318, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.