Ignite Creation Date:
2024-05-05 @ 10:44 PM
Last Modification Date:
2024-10-26 @ 10:23 AM
Study NCT ID:
NCT01172509
Status:
TERMINATED
Last Update Posted:
2015-08-21
First Post:
2010-07-28
Brief Title:
TMS Measures of Plasticity and ExcitatoryInhibitory Ratio as Biomarkers R-baclofen Effects in Normal Volunteers
Sponsor:
Gonzalez-Heydrich Joseph MD
Organization:
Gonzalez-Heydrich Joseph MD
Study Overview
Official Title:
Transcranial Magnetic Stimulation TMS Measures of Plasticity and ExcitatoryInhibitory Ratio as Biomarkers for R-baclofen Effects in Normal Volunteers
Status:
TERMINATED
Status Verified Date:
2015-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
too much variability in the TMS measures
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Our overall objective is to apply Transcranial Magnetic Stimulation TMS to develop measures of human synaptic plasticity and of brain excitatoryinhibitory ratio EI ratio which we propose as novel biomarkers and outcome measures that will expedite clinical trials of treatments for Autism Spectrum Disorder ASD One potential therapeutic agent R-baclofen will be investigated under this protocol
TMS is a safe inexpensive and noninvasive means to focally stimulate the human brain Presently TMS is in extensive use as a means to measure regional brain excitability which is dependent on local synaptic strength TMS can be used to temporarily alter synaptic strength as well as to acutely measure levels of cortical excitability and short and long interval inhibition Since altered synaptic plasticity and an imbalanced inhibitoryexcitatory ratio are cited as fundamental abnormalities in ASD we hypothesize that both severity of ASD-related learning deficits and their improvement after therapy will correlate with TMS measures of synaptic plasticity and EI ratio We propose to embed TMS measures of synaptic plasticity and EI ratio in a Proof of Principal trial of R-baclofen and to examine
Aim 1 Whether R-baclofen a potential therapeutic agent for ASD predictably alters TMS measures of synaptic plasticity and EI ratio as a function of plasma concentration in adult volunteers We will test the following hypotheses
1 R-baclofen produces a significant change in TMS measures of LTD and EI ratio and
2 R-baclofen plasma levels and TMS measures of LTD and EI ratio show a predictable exposure-response relationship
Exploratory Aim 1 Whether the presence of genetic polymorphisms of the BDNF and GABA-B receptor genes has a moderating effect on TMS measures and on R-baclofen effects We will test the following hypotheses
1 Presence of the BDNF val66met allele will be associated with decreased long-term depression LTD of cortical excitability
2 Polymorphisms of GABA-B receptor genes will be associated with altered magnitude of response to R-baclofen as measured by TMS
TMS is a safe inexpensive and noninvasive means to focally stimulate the human brain Presently TMS is in extensive use as a means to measure regional brain excitability which is dependent on local synaptic strength TMS can be used to temporarily alter synaptic strength as well as to acutely measure levels of cortical excitability and short and long interval inhibition Since altered synaptic plasticity and an imbalanced inhibitoryexcitatory ratio are cited as fundamental abnormalities in ASD we hypothesize that both severity of ASD-related learning deficits and their improvement after therapy will correlate with TMS measures of synaptic plasticity and EI ratio We propose to embed TMS measures of synaptic plasticity and EI ratio in a Proof of Principal trial of R-baclofen and to examine
Aim 1 Whether R-baclofen a potential therapeutic agent for ASD predictably alters TMS measures of synaptic plasticity and EI ratio as a function of plasma concentration in adult volunteers We will test the following hypotheses
1 R-baclofen produces a significant change in TMS measures of LTD and EI ratio and
2 R-baclofen plasma levels and TMS measures of LTD and EI ratio show a predictable exposure-response relationship
Exploratory Aim 1 Whether the presence of genetic polymorphisms of the BDNF and GABA-B receptor genes has a moderating effect on TMS measures and on R-baclofen effects We will test the following hypotheses
1 Presence of the BDNF val66met allele will be associated with decreased long-term depression LTD of cortical excitability
2 Polymorphisms of GABA-B receptor genes will be associated with altered magnitude of response to R-baclofen as measured by TMS
Detailed Description:
The design is a double-blind placebo controlled 5 way crossover trial of a single dose each of placebo x 2 0 mg 3 10 and 25 mg of R-baclofen followed by plasma levels at 0 30 60 90 and 140 minutes after each dose and TMS testing at 0 30 60 90 cTBS application at 90 minute time point 95 and then periodically every 5-10 minutes until the MEPs return to baseline There will be a total of 7 visits Patients will come in for a screening visit then scheduled to return for 1 baseline visit cTBS without drug and 5 crossover visits At each crossover visit a venous line will be placed for blood sampling and a single dose of study drug at one of the five dose levels will be given orally at time 0 There will be a one-week washout between each of the crossover arms R-baclofen has a mean Tmax of approximately 80 minutes and a terminal half life of 49 hour
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None