Bethesda, Maryland 20892


Purpose:

Background: - Brain activity changes with changes in body temperature. Brain activity can be studied with a procedure called transcranial magnetic stimulation (TMS). Researchers want to cool the brain through the scalp using a cooling cap. They want to see if cooling changes the brain and body s response to TMS. Objectives: - To look at the effects of cooling on the brain. Eligibility: - Right-handed adults age 18-50 who can abstain from caffeine and tobacco. Design: - Participants will be screened with medical history and physical exam. They will be asked about alcohol use, smoking, and substance abuse. They may take a pregnancy test. They may have a magnetic resonance imaging (MRI) scan of the brain. For MRI, participants lie on a table that slides in and out of a metal tube that takes pictures. - Participants will have 3 outpatient visits. The following procedures will occur at each visit. - Participants will wear a cooling cap for up to 45 minutes. Cool water will flow through the cap. It will feel like an ice pack in a towel. Their core temperature will be monitored. Their temperature will also be measured under their tongue and on scalp, stomach, forearm, and calf. - Participants will have TMS before and after wearing the cap. A brief electrical current will pass through a wire coil held on their scalp. Electrodes that detect muscle movement will be placed on their hand. They will also have repetitive TMS, which uses repeated magnetic pulses. Their wrist will also receive a shock.


Study summary:

1. Objective The dysregulation of synaptic transmission in certain brain areas may be responsible for some neurological disorders. It was demonstrated that synaptic transmission may be modulated through repetitive transcranial magnetic stimulation (rTMS), and this may be a component of the therapeutic effects of rTMS. However, rTMS utility is limited due to an inability to focus the stimulation. Cooling was shown to reduce the neuronal activity in targeted brain areas. The goal of this protocol is to examine the ability of cooling to affect rTMS. 2. Study population We intend to study 18 adult healthy volunteers on an outpatient basis. The accrual ceiling requested is 23 subjects to allow for dropouts and screening failures. We intend to perform a sub-study to develop a new method of plasticity induction phase-triggered paired associative stimulation. This sub-study requires an additional intended study population of 10 subjects who may be a sub-set of the initially requested 18 subjects from the main study. The additional accrual ceiling is 12 subjects to allow for dropouts and screening failures. The total ceiling for the entire protocol is 35. 3. Design We propose using rapid-rate paired associative stimulation (rPAS), modulated by applying cooling to the scalp, to examine the effect of cooling on rTMS. Our hypothesis is that cooling the brain will prevent the potentiation normally induced by rPAS. We will reduce brain temperature by up to 1.5 degrees Celsius by applying a cooling helmet to the scalp and then test the effect on potentiation by applying rPAS. One of our stopping criterion will be reduction in measured temperature reduction by 2 degrees Celsius. This study consists of one experiment with18 subjects. The experiment is divided into three session visits, each to be carried out at least 1 day apart. The control potentiation in response to rPAS without cooling will be measured during session visit 1 by using the TMS-evoked motor evoked potential (MEP). In session visit 2, after applying a commercially available liquid cooling helmet for 45 minutes to reduce the temperature of the underlying cerebral cortex by up to 1.5 degrees Celsius, we will then assess the response to rPAS. In session 3, the MEP will be measured after applying the cooling helmet but with the rPAS procedure substituted with a sham rPAS. Session visit 3 is necessary to determine if there are any changes to the MEP in response to cooling alone. Thus, in the three session visits, we will evaluate cooling alone, rPAS alone, and the two together. The proposed sub-study is to develop a method to improve the reliability of the primary endpoint. The new method will utilize EEG phase-triggered paired associative stimulation. Similarly to the rapid-rate paired associative stimulation (rPAS) used in the main study, EEG phase-triggered paired associative stimulation also uses paired median nerve stimulation with TMS to motor cortex. However, the stimuli are triggered when the EEG is at a prespecified phase of the alpha-band (8-12 Hz) oscillation. The sub-study to develop the optimal parameters of phase-triggered paired associative stimulation will consist of 3 arms. Two active arms will trigger the paired median nerve and motor cortex TMS according to the phase of the ongoing EEG. The first arm will trigger the stimuli at the trough of the ongoing EEG (phase -90 if the EEG is modeled as a sine wave). The second arm will trigger the stimul at the peak of the ongoing EEG (phase +90). The third control arm will trigger the paired stimuli at a random delay from the through of the ongoing EEG. This control arm serves to deliver paired stimuli at a rate matched to the ongoing EEG, but stimulates at a random phase of each alpha oscillation cycle. Our hypothesis is that stimulating at the through of the ongoing EEG will result in increased plastic changes to the brain as measured through our TMS outcome measures of single pulse MEPs, as compared to the control condition of random phase stimulation. We also hypothesize that stimulating at the peak of the ongoing EEG will result in a decrease in TMS outcome measures as compared to the control arm. This will be a withinsubject design of 3 visits for each of the 10 sub-study subjects. 4. Outcome measures The primary outcome measure will be the amplitude of MEPs induced by single TMS pulses


Criteria:

- INCLUSION CRITERIA: To be eligible for this research study participants must: - Be between 18 and 50 years of age. - Be right-handed. - Able to abstain from food or drinks containing caffeine 24 hours before the last 3 session visits. The screening visit does not require the ability to abstain from food or drinks containing caffeine. - Able to abstain from tobacco on the day of the last three session visits. The screening visit doesn t require the ability to abstain from tobacco. EXCLUSION CRITERIA: Participants will be excluded from this research study if they: - Are taking medications of the following classes: antidepressants, anxiolytics, anticonvulsants, antipsychotics, antiparkinson, hypnotics, stimulants, and antihistamines. - Have a heart rate that exceeds 100 bpm (resting tachycardia). - Have a history of psychiatric condition(s). - Have a neurologic disorder such as a history of brain tumor, stroke, central nervous system infection, epilepsy, cerebrovascular disease, dementia, head trauma, or increased intracranial pressure. - Have surgically or traumatically implanted metallic foreign bodies such as, pacemakers, medication pumps, implanted hearing aids, defibrillators, metal plates in the skull or metal implants in the skull or eyes (other than dental fillings), intracardiac lines, or any other condition/device that might be physically hazardous during TMS or magnetic resonance imaging (MRI), or might distort the images. - Are unable to lie flat on back for up to 1 hour. - Have claustrophobia or a feeling of discomfort from being in small, enclosed spaces of enough severity to prevent MRI scanning. - Are pregnant or have a positive pregnancy test before the research procedure due to -the risks associated with MRI scans. - Have abnormal findings in clinical MRI that we will do during the screening visit. - Have any abnormal or focal finding on the neurological exam.<TAB> - Have a known hearing loss. - Have an alcohol or substance abuse problem, as determined by the Alcohol, Smoking and Substance Abuse Screening Test (ASSIST). - Have sensitivity to coldness.(main experiment only, not an exclusion for the sub-study which does not utilize cooling)


NCT ID:

NCT02363296


Primary Contact:

Principal Investigator
Mark Hallett, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)

Elaine P Considine, R.N.
Phone: (301) 435-8518
Email: considinee@ninds.nih.gov


Backup Contact:

Email: hallettm@ninds.nih.gov
Mark Hallett, M.D.
Phone: (301) 496-9526


Location Contact:

Bethesda, Maryland 20892
United States

For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)
Phone: 800-411-1222
Email: prpl@mail.cc.nih.gov

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 21, 2017

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