Trial Outcomes & Findings for Role of the Supraspinal Opioidergic Circuit in Prefrontal TMS-Induced Analgesia (NCT NCT01643798)
NCT ID: NCT01643798
Last Updated: 2014-04-15
Results Overview
There are two experimental visits separated by one week. During each experiment, pain ratings will be measured every 30 minutes. "Preliminary testing" will be done 30 minutes into the experiment. The purpose of preliminary testing is to select the temperature that will be used to induce pain throughout the experiment. "Baseline testing" will be done 60 minutes into the experiment. "After sham rTMS" will be done 90 minutes into the experiment. "After real rTMS" will be done 120 minutes into the study. The pain scale used in a Visual Analog Scale (VAS). There was an 11-point rating system where "0" represented no pain and "10" represented unbearable pain.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
15 participants
Primary outcome timeframe
Baseline (60 minutes into experiment), Post-Sham (90 minutes), Post-Real (120 minutes)
Results posted on
2014-04-15
Participant Flow
Prospective participants were interviewed over the phone prior to being invited to a screening visit in the Brain Stimulation Laboratory at MUSC. Risks and benefits were explained and consent was obtained. All participants were tested for opiate use and females were tested for pregnancy. Recruitment began in 2011 and ended in early 2012.
Healthy volunteers were randomized to receive I.V. saline or naloxone immediately prior to sham and real rTMS on the same experimental visit. One week later, each participant received the novel pretreatment but the same stimulation paradigm. One participant dropped out after her first experimental visit. These data were not included.
Participant milestones
| Measure |
Saline and Stimulation, Then Naloxone and Stimulation
Participants received an intravenous infusion of 10ml sterile saline immediately prior to sham and real rTMS of the left dorsolateral prefrontal cortex. One week later, participants received an intravenous infusion of 0.1 mg/kg Naloxone immediately prior to sham and real rTMS of the left dorsolateral prefrontal cortex
|
Naloxone and Stimulation, Then Saline and Stimulation
Participants received an intravenous infusion of 0.1mg/kg Naloxone immediately prior to sham and real rTMS of the left dorsolateral prefrontal cortex. One week later, participants received an intravenous infusion of 10ml sterile saline immediately prior to sham and real rTMS of the left dorsolateral prefrontal cortex
|
|---|---|---|
|
Pretreatment 1 and Stimulation
STARTED
|
7
|
8
|
|
Pretreatment 1 and Stimulation
COMPLETED
|
6
|
8
|
|
Pretreatment 1 and Stimulation
NOT COMPLETED
|
1
|
0
|
|
Pretreatment 2 and Stimulation
STARTED
|
6
|
8
|
|
Pretreatment 2 and Stimulation
COMPLETED
|
6
|
8
|
|
Pretreatment 2 and Stimulation
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Saline and Stimulation, Then Naloxone and Stimulation
Participants received an intravenous infusion of 10ml sterile saline immediately prior to sham and real rTMS of the left dorsolateral prefrontal cortex. One week later, participants received an intravenous infusion of 0.1 mg/kg Naloxone immediately prior to sham and real rTMS of the left dorsolateral prefrontal cortex
|
Naloxone and Stimulation, Then Saline and Stimulation
Participants received an intravenous infusion of 0.1mg/kg Naloxone immediately prior to sham and real rTMS of the left dorsolateral prefrontal cortex. One week later, participants received an intravenous infusion of 10ml sterile saline immediately prior to sham and real rTMS of the left dorsolateral prefrontal cortex
|
|---|---|---|
|
Pretreatment 1 and Stimulation
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Role of the Supraspinal Opioidergic Circuit in Prefrontal TMS-Induced Analgesia
Baseline characteristics by cohort
| Measure |
Pretreatment & Stimulation
n=15 Participants
Outside of the 3T magnetic resonance imaging (MRI) scanner, participants underwent resting motor threshold assessment, left dorsolateral prefrontal cortex localization and preliminary pain testing. Next, participants were placed in the scanner for baseline pain testing. After baseline testing, participants were asked to rate the pain that they had experienced. Participants were subsequently removed from the scanner and randomized to receive approximately 10 ml intravenous naloxone (0.1mg/kg) or saline immediately prior to 20 minutes of sham left DLFPC rTMS. Following sham rTMS, participants returned to the scanner for the same block testing performed at baseline. After rating their pain, participants were removed from the scanner for 20 minutes of real left DLPFC rTMS. Participants then returned to the scanner for the final block test.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
26 years
STANDARD_DEVIATION 4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (60 minutes into experiment), Post-Sham (90 minutes), Post-Real (120 minutes)There are two experimental visits separated by one week. During each experiment, pain ratings will be measured every 30 minutes. "Preliminary testing" will be done 30 minutes into the experiment. The purpose of preliminary testing is to select the temperature that will be used to induce pain throughout the experiment. "Baseline testing" will be done 60 minutes into the experiment. "After sham rTMS" will be done 90 minutes into the experiment. "After real rTMS" will be done 120 minutes into the study. The pain scale used in a Visual Analog Scale (VAS). There was an 11-point rating system where "0" represented no pain and "10" represented unbearable pain.
Outcome measures
| Measure |
Sham rTMS With Saline
n=14 Participants
Participants first underwent baseline pain testing in the scanner. At the conclusion of baseline testing, participants were asked to rate the pain that they had experienced. Participants were subsequently removed from the scanner and randomized to receive 10 ml intravenous (I.V.) naloxone (0.1 mg/kg) or saline immediately before 20 min of sham left DLFPC rTMS. Following sham rTMS, participants returned to the scanner for the same block testing performed at baseline. After rating their pain, participants were removed from the scanner for 20min of real left DLPFC rTMS. Participants then returned to the scanner for the final block test. The I.V. pretreatment was randomized such that participants received saline on one visit and naloxone on the other visit.
|
Real rTMS With Saline
n=14 Participants
Participants first underwent baseline pain testing in the scanner. At the conclusion of baseline testing, participants were asked to rate the pain that they had experienced. Participants were subsequently removed from the scanner and randomized to receive 10 ml intravenous (I.V.) naloxone (0.1 mg/kg) or saline immediately before 20 min of sham left DLFPC rTMS. Following sham rTMS, participants returned to the scanner for the same block testing performed at baseline. After rating their pain, participants were removed from the scanner for 20min of real left DLPFC rTMS. Participants then returned to the scanner for the final block test. The I.V. pretreatment was randomized such that participants received saline on one visit and naloxone on the other visit.
|
Sham rTMS With Naloxone
n=14 Participants
Participants first underwent baseline pain testing in the scanner. At the conclusion of baseline testing, participants were asked to rate the pain that they had experienced. Participants were subsequently removed from the scanner and randomized to receive 10 ml intravenous (I.V.) naloxone (0.1 mg/kg) or saline immediately before 20 min of sham left DLFPC rTMS. Following sham rTMS, participants returned to the scanner for the same block testing performed at baseline. After rating their pain, participants were removed from the scanner for 20min of real left DLPFC rTMS. Participants then returned to the scanner for the final block test. The I.V. pretreatment was randomized such that participants received saline on one visit and naloxone on the other visit.
|
Real rTMS With Naloxone
n=14 Participants
Participants first underwent baseline pain testing in the scanner. At the conclusion of baseline testing, participants were asked to rate the pain that they had experienced. Participants were subsequently removed from the scanner and randomized to receive 10 ml intravenous (I.V.) naloxone (0.1 mg/kg) or saline immediately before 20 min of sham left DLFPC rTMS. Following sham rTMS, participants returned to the scanner for the same block testing performed at baseline. After rating their pain, participants were removed from the scanner for 20min of real left DLPFC rTMS. Participants then returned to the scanner for the final block test. The I.V. pretreatment was randomized such that participants received saline on one visit and naloxone on the other visit.
|
|---|---|---|---|---|
|
Pain Rating
|
7.36 units on a scale
Standard Error 0.24
|
5.61 units on a scale
Standard Error 0.26
|
7.54 units on a scale
Standard Error 0.15
|
6.75 units on a scale
Standard Error 0.21
|
PRIMARY outcome
Timeframe: Baseline (60 minutes into experiment), Post-Sham (90 minutes), Post-Real (120 minutes)There are two experimental visits separated by one week. During each experiment, blood oxygen level dependent (BOLD) signal will be measured at baseline (60 minutes into the experiment), post-sham rTMS (90 minutes into the experiment) and post-real (120 minutes into the experiment).
Outcome measures
| Measure |
Sham rTMS With Saline
n=14 Participants
Participants first underwent baseline pain testing in the scanner. At the conclusion of baseline testing, participants were asked to rate the pain that they had experienced. Participants were subsequently removed from the scanner and randomized to receive 10 ml intravenous (I.V.) naloxone (0.1 mg/kg) or saline immediately before 20 min of sham left DLFPC rTMS. Following sham rTMS, participants returned to the scanner for the same block testing performed at baseline. After rating their pain, participants were removed from the scanner for 20min of real left DLPFC rTMS. Participants then returned to the scanner for the final block test. The I.V. pretreatment was randomized such that participants received saline on one visit and naloxone on the other visit.
|
Real rTMS With Saline
n=14 Participants
Participants first underwent baseline pain testing in the scanner. At the conclusion of baseline testing, participants were asked to rate the pain that they had experienced. Participants were subsequently removed from the scanner and randomized to receive 10 ml intravenous (I.V.) naloxone (0.1 mg/kg) or saline immediately before 20 min of sham left DLFPC rTMS. Following sham rTMS, participants returned to the scanner for the same block testing performed at baseline. After rating their pain, participants were removed from the scanner for 20min of real left DLPFC rTMS. Participants then returned to the scanner for the final block test. The I.V. pretreatment was randomized such that participants received saline on one visit and naloxone on the other visit.
|
Sham rTMS With Naloxone
n=14 Participants
Participants first underwent baseline pain testing in the scanner. At the conclusion of baseline testing, participants were asked to rate the pain that they had experienced. Participants were subsequently removed from the scanner and randomized to receive 10 ml intravenous (I.V.) naloxone (0.1 mg/kg) or saline immediately before 20 min of sham left DLFPC rTMS. Following sham rTMS, participants returned to the scanner for the same block testing performed at baseline. After rating their pain, participants were removed from the scanner for 20min of real left DLPFC rTMS. Participants then returned to the scanner for the final block test. The I.V. pretreatment was randomized such that participants received saline on one visit and naloxone on the other visit.
|
Real rTMS With Naloxone
n=14 Participants
Participants first underwent baseline pain testing in the scanner. At the conclusion of baseline testing, participants were asked to rate the pain that they had experienced. Participants were subsequently removed from the scanner and randomized to receive 10 ml intravenous (I.V.) naloxone (0.1 mg/kg) or saline immediately before 20 min of sham left DLFPC rTMS. Following sham rTMS, participants returned to the scanner for the same block testing performed at baseline. After rating their pain, participants were removed from the scanner for 20min of real left DLPFC rTMS. Participants then returned to the scanner for the final block test. The I.V. pretreatment was randomized such that participants received saline on one visit and naloxone on the other visit.
|
|---|---|---|---|---|
|
Change in BOLD Signal in Pain Processing Regions During Pain, Including Supraspinal Opioidergic Structures
|
0.15 mean percentage of BOLD signal change
Standard Error 0.03
|
0.00 mean percentage of BOLD signal change
Standard Error 0.04
|
0.10 mean percentage of BOLD signal change
Standard Error 0.03
|
0.13 mean percentage of BOLD signal change
Standard Error 0.05
|
Adverse Events
Pretreatment & Stimulation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place