Clinical trial NCT01819675: Effect of Repetitive Transcranial Magnetic Stimulation (rTMS) Over the Brain on the Neurotransmitter Binding
Official title: Effect of rTMS Over Primary Motor Cortex on Gamma-aminobutyric Acid A (GABAA)-[18F]Flumazenil Binding: A Positron Emission Tomography (PET) Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Stroke
Hemiplegia
Keywords: Neuronal plasticity
Neurotransmitter agents
Receptors, neurotransmitter
Transcranial magnetic stimulation
Stroke
gamma-Aminobutyric Acid
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Health & Welfare, Korea
First posted: 2013-03-27
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to determine whether repetitive transcranial magnetic stimulation (rTMS) over the brain can modulate the binding of neurotransmitter (GABA in this study) to its receptor using the special PET study.

Detailed description: Repetitive transcranial magnetic stimulation (rTMS) can modulate the excitability of cortex but exact mechanism is not well determined in human-beings. Changes in some neurotransmitters' status in brain after rTMS have been suggested as a possible mechanism, but role of GABA is not clear.

Twelve healthy people will be recruited. They will receive the rTMS over the primary motor cortex of the dominant hand. Individual subject will receive three sessions of rTMS with wash-out period (more than 3 days) between the rTMS sessions. Three rTMS sessions are high frequency (10Hz), low frequency (1Hz) and sham rTMS. The order of rTMS sessions will be randomly decided. After completing each rTMS session, \[18F\]flumazenil-PET will be checked.

The purpose of this study is to investigate 1)whether rTMS over the primary motor cortex can modulate the \[18F\]flumazenil binding potential and 2)whether the modulation of \[18F\]flumazenil binding potential by rTMS can be different according to the applied frequency of rTMS.

Eligibility criteria: Inclusion Criteria:

* Healthy people
* 18-50 yrs old
* Right handedness
* Written informed consent

Exclusion Criteria:

* Previous medical diseases such as seizure, stroke, diabetes, hypertension.
* Taking any drugs
* Smoker
* Pregnancy
* Contraindication of PET or MRI
* Stroke or any tumor in MRI
* Metals objects in the head or eyes
* Cardiac pacemaker or cochlear implant

Primary outcomes:
measure: [18F]flumazenil binding potential
timeFrame: up to 3 months
Secondary outcomes:
measure: Purdue pegboard test score
timeFrame: Before rTMS (baseline) and average 2hours after rTMS
Other outcomes:
Locations:
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
Study officials:
affiliation: Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
name: Nam-Jong Paik, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ayache SS, Farhat WH, Zouari HG, Hosseini H, Mylius V, Lefaucheur JP. Stroke rehabilitation using noninvasive cortical stimulation: motor deficit. Expert Rev Neurother. 2012 Aug;12(8):949-72. doi: 10.1586/ern.12.83.
citation: Malenka RC, Bear MF. LTP and LTD: an embarrassment of riches. Neuron. 2004 Sep 30;44(1):5-21. doi: 10.1016/j.neuron.2004.09.012.
citation: Thickbroom GW. Transcranial magnetic stimulation and synaptic plasticity: experimental framework and human models. Exp Brain Res. 2007 Jul;180(4):583-93. doi: 10.1007/s00221-007-0991-3. Epub 2007 Jun 12.
citation: Yue L, Xiao-lin H, Tao S. The effects of chronic repetitive transcranial magnetic stimulation on glutamate and gamma-aminobutyric acid in rat brain. Brain Res. 2009 Mar 13;1260:94-9. doi: 10.1016/j.brainres.2009.01.009. Epub 2009 Jan 12.
citation: Trippe J, Mix A, Aydin-Abidin S, Funke K, Benali A. theta burst and conventional low-frequency rTMS differentially affect GABAergic neurotransmission in the rat cortex. Exp Brain Res. 2009 Dec;199(3-4):411-21. doi: 10.1007/s00221-009-1961-8.