Trial Outcomes & Findings for Non-Invasive Vagal Nerve Stimulation in Opioid Use Disorders (NCT NCT04556552)
NCT ID: NCT04556552
Last Updated: 2023-09-13
Results Overview
Opioid craving will be measured based on Visual Analogue Scale (VAS) VAS consist in 10-point lines anchored with "not at all" on one end and "extremely" on the other where participants report the extent to which they felt any craving for opiates, severity of withdrawal symptoms, and the extent to which the study intervention has helped to ease the cravings. Total possible score ranges from 0 to100, with 100 correlating with worse study outcome.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
20 participants
Primary outcome timeframe
Baseline, 5 minutes post-intervention
Results posted on
2023-09-13
Participant Flow
Participant milestones
| Measure |
Active Non-invasive Vagal Nerve Stimulation (VNS)
Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.
Non invasive VN stimulation (nVNS): Stimulation of vagus nerve with active device.
Participants will be administered nVNS using the electroCore GammaCore-S non-invasive VNS device. The intensity of the stimulus will be adjusted by the user, to the maximum tolerable level to ensure nVNS without causing excessive pain, the burst frequency to 5 kHz, and the envelope frequency to 25 Hz.
The duration of delivery will be 2 minutes, and the beginning will coincide with initiation of acquisition of the HR-PET scan which will be 90 seconds in duration; following an additional 8 minutes, a second VNS delivery will be administered, in conjunction with which another scan will be obtained.
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
|
Sham Stimulation
Sham stimulation of vagus with opioid cues
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
Sham Stimulation: Sham stimulation of vagus during opioid cue exposure. Each subject in the "SHAM" group will undergo the action of administering the intervention, but the device will be programmed such that the stimulation will not activate the vagus nerve.
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
8
|
|
Overall Study
COMPLETED
|
11
|
6
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Active Non-invasive Vagal Nerve Stimulation (VNS)
Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.
Non invasive VN stimulation (nVNS): Stimulation of vagus nerve with active device.
Participants will be administered nVNS using the electroCore GammaCore-S non-invasive VNS device. The intensity of the stimulus will be adjusted by the user, to the maximum tolerable level to ensure nVNS without causing excessive pain, the burst frequency to 5 kHz, and the envelope frequency to 25 Hz.
The duration of delivery will be 2 minutes, and the beginning will coincide with initiation of acquisition of the HR-PET scan which will be 90 seconds in duration; following an additional 8 minutes, a second VNS delivery will be administered, in conjunction with which another scan will be obtained.
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
|
Sham Stimulation
Sham stimulation of vagus with opioid cues
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
Sham Stimulation: Sham stimulation of vagus during opioid cue exposure. Each subject in the "SHAM" group will undergo the action of administering the intervention, but the device will be programmed such that the stimulation will not activate the vagus nerve.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Claustrophobia
|
0
|
1
|
|
Overall Study
Inability to continue
|
0
|
1
|
Baseline Characteristics
Non-Invasive Vagal Nerve Stimulation in Opioid Use Disorders
Baseline characteristics by cohort
| Measure |
Active Non-invasive Vagal Nerve Stimulation (VNS)
n=12 Participants
Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.
Non invasive VN stimulation (nVNS): Stimulation of vagus nerve with active device.
Participants will be administered nVNS using the electroCore GammaCore-S non-invasive VNS device. The intensity of the stimulus will be adjusted by the user, to the maximum tolerable level to ensure nVNS without causing excessive pain, the burst frequency to 5 kHz, and the envelope frequency to 25 Hz.
The duration of delivery will be 2 minutes, and the beginning will coincide with initiation of acquisition of the HR-PET scan which will be 90 seconds in duration; following an additional 8 minutes, a second VNS delivery will be administered, in conjunction with which another scan will be obtained.
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
|
Sham Stimulation
n=8 Participants
Sham stimulation of vagus with opioid cues
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
Sham Stimulation: Sham stimulation of vagus during opioid cue exposure. Each subject in the "SHAM" group will undergo the action of administering the intervention, but the device will be programmed such that the stimulation will not activate the vagus nerve.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41.5 years
STANDARD_DEVIATION 13.857 • n=5 Participants
|
48.375 years
STANDARD_DEVIATION 9.366 • n=7 Participants
|
44.25 years
STANDARD_DEVIATION 15.348 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
8 participants
n=7 Participants
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 5 minutes post-interventionPopulation: Number analyzed in one or more rows differs from overall number analyzed because some data was not collected for technical reasons.
Opioid craving will be measured based on Visual Analogue Scale (VAS) VAS consist in 10-point lines anchored with "not at all" on one end and "extremely" on the other where participants report the extent to which they felt any craving for opiates, severity of withdrawal symptoms, and the extent to which the study intervention has helped to ease the cravings. Total possible score ranges from 0 to100, with 100 correlating with worse study outcome.
Outcome measures
| Measure |
Active Non-invasive Vagal Nerve Stimulation (VNS)
n=11 Participants
Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.
Non invasive VN stimulation (nVNS): Stimulation of vagus nerve with active device.
Participants will be administered nVNS using the electroCore GammaCore-S non-invasive VNS device. The intensity of the stimulus will be adjusted by the user, to the maximum tolerable level to ensure nVNS without causing excessive pain, the burst frequency to 5 kHz, and the envelope frequency to 25 Hz.
The duration of delivery will be 2 minutes, and the beginning will coincide with initiation of acquisition of the HR-PET scan which will be 90 seconds in duration; following an additional 8 minutes, a second VNS delivery will be administered, in conjunction with which another scan will be obtained.
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
|
Sham Stimulation
n=7 Participants
Sham stimulation of vagus with opioid cues
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
Sham Stimulation: Sham stimulation of vagus during opioid cue exposure. Each subject in the "SHAM" group will undergo the action of administering the intervention, but the device will be programmed such that the stimulation will not activate the vagus nerve.
|
|---|---|---|
|
Opioid Craving Using Visual Analogue Scale
Baseline
|
3.909 score on a scale
Standard Deviation 3.048
|
6 score on a scale
Standard Deviation 2.160
|
|
Opioid Craving Using Visual Analogue Scale
5 min post-intervention
|
4.556 score on a scale
Standard Deviation 2.186
|
5.5 score on a scale
Standard Deviation 3.937
|
PRIMARY outcome
Timeframe: Baseline, two minutes post-interventionHeart rate will be measured after cue. Decreased HR correlates with better outcome.
Outcome measures
| Measure |
Active Non-invasive Vagal Nerve Stimulation (VNS)
n=11 Participants
Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.
Non invasive VN stimulation (nVNS): Stimulation of vagus nerve with active device.
Participants will be administered nVNS using the electroCore GammaCore-S non-invasive VNS device. The intensity of the stimulus will be adjusted by the user, to the maximum tolerable level to ensure nVNS without causing excessive pain, the burst frequency to 5 kHz, and the envelope frequency to 25 Hz.
The duration of delivery will be 2 minutes, and the beginning will coincide with initiation of acquisition of the HR-PET scan which will be 90 seconds in duration; following an additional 8 minutes, a second VNS delivery will be administered, in conjunction with which another scan will be obtained.
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
|
Sham Stimulation
n=6 Participants
Sham stimulation of vagus with opioid cues
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
Sham Stimulation: Sham stimulation of vagus during opioid cue exposure. Each subject in the "SHAM" group will undergo the action of administering the intervention, but the device will be programmed such that the stimulation will not activate the vagus nerve.
|
|---|---|---|
|
Heart Rate (HR)
Baseline
|
64.357 bpm
Standard Deviation 8.275
|
61.575 bpm
Standard Deviation 10.715
|
|
Heart Rate (HR)
Two minutes post-intervention
|
64.192 bpm
Standard Deviation 9.960
|
59.003 bpm
Standard Deviation 10.182
|
PRIMARY outcome
Timeframe: Baseline, 2 minutes post-interventionPre-ejection Period (PEP) is a marker of cardiac sympathetic tone that is increased with blocked sympathetic function. Higher PEP correlates with better outcome.
Outcome measures
| Measure |
Active Non-invasive Vagal Nerve Stimulation (VNS)
n=11 Participants
Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.
Non invasive VN stimulation (nVNS): Stimulation of vagus nerve with active device.
Participants will be administered nVNS using the electroCore GammaCore-S non-invasive VNS device. The intensity of the stimulus will be adjusted by the user, to the maximum tolerable level to ensure nVNS without causing excessive pain, the burst frequency to 5 kHz, and the envelope frequency to 25 Hz.
The duration of delivery will be 2 minutes, and the beginning will coincide with initiation of acquisition of the HR-PET scan which will be 90 seconds in duration; following an additional 8 minutes, a second VNS delivery will be administered, in conjunction with which another scan will be obtained.
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
|
Sham Stimulation
n=6 Participants
Sham stimulation of vagus with opioid cues
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
Sham Stimulation: Sham stimulation of vagus during opioid cue exposure. Each subject in the "SHAM" group will undergo the action of administering the intervention, but the device will be programmed such that the stimulation will not activate the vagus nerve.
|
|---|---|---|
|
Pre-ejection Period (PEP)
Baseline
|
0.048 seconds
Standard Deviation 0.033
|
0.069 seconds
Standard Deviation 0.035
|
|
Pre-ejection Period (PEP)
2 minutes post-intervention
|
0.050 seconds
Standard Deviation 0.0320
|
0.066 seconds
Standard Deviation 0.0312
|
PRIMARY outcome
Timeframe: Baseline, 2 minutes post-interventionPhotoplethysmography (PPG) amplitude reflects vasoconstriction in figure blood vessel. PPG amplitude is increased with blocked sympathetic tone and higher PPG correlates with better outcome.
Outcome measures
| Measure |
Active Non-invasive Vagal Nerve Stimulation (VNS)
n=11 Participants
Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.
Non invasive VN stimulation (nVNS): Stimulation of vagus nerve with active device.
Participants will be administered nVNS using the electroCore GammaCore-S non-invasive VNS device. The intensity of the stimulus will be adjusted by the user, to the maximum tolerable level to ensure nVNS without causing excessive pain, the burst frequency to 5 kHz, and the envelope frequency to 25 Hz.
The duration of delivery will be 2 minutes, and the beginning will coincide with initiation of acquisition of the HR-PET scan which will be 90 seconds in duration; following an additional 8 minutes, a second VNS delivery will be administered, in conjunction with which another scan will be obtained.
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
|
Sham Stimulation
n=6 Participants
Sham stimulation of vagus with opioid cues
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
Sham Stimulation: Sham stimulation of vagus during opioid cue exposure. Each subject in the "SHAM" group will undergo the action of administering the intervention, but the device will be programmed such that the stimulation will not activate the vagus nerve.
|
|---|---|---|
|
Photoplethysmography (PPG) Amplitude
Baseline
|
1.411 AU (arbitrary units)
Standard Deviation 1.285
|
1.684 AU (arbitrary units)
Standard Deviation 0.838
|
|
Photoplethysmography (PPG) Amplitude
2 minutes post-intervention
|
1.162 AU (arbitrary units)
Standard Deviation 2.312
|
1.459 AU (arbitrary units)
Standard Deviation 0.873
|
PRIMARY outcome
Timeframe: Baseline, 2 minutes post-interventionBrain blood flow measured with Positron Emission Tomography (PET) and radiolabeled water at baseline and 2 min post-intervention during viewing of neutral videos and with active and Sham VNS stimulation paired with opioid use videos. Brain blood flow was measured in mL per 100 g of tissue per minute (mL/100g/min) normalized to a reference of 50 ml/100 g of tissue per minute.
Outcome measures
| Measure |
Active Non-invasive Vagal Nerve Stimulation (VNS)
n=7 Participants
Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.
Non invasive VN stimulation (nVNS): Stimulation of vagus nerve with active device.
Participants will be administered nVNS using the electroCore GammaCore-S non-invasive VNS device. The intensity of the stimulus will be adjusted by the user, to the maximum tolerable level to ensure nVNS without causing excessive pain, the burst frequency to 5 kHz, and the envelope frequency to 25 Hz.
The duration of delivery will be 2 minutes, and the beginning will coincide with initiation of acquisition of the HR-PET scan which will be 90 seconds in duration; following an additional 8 minutes, a second VNS delivery will be administered, in conjunction with which another scan will be obtained.
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
|
Sham Stimulation
n=4 Participants
Sham stimulation of vagus with opioid cues
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
Sham Stimulation: Sham stimulation of vagus during opioid cue exposure. Each subject in the "SHAM" group will undergo the action of administering the intervention, but the device will be programmed such that the stimulation will not activate the vagus nerve.
|
|---|---|---|
|
Brain Blood Flow in the Anterior Cingulate With VNS Paired With Opioid Use Videos
Baseline
|
56.1 mL/100g/min
Standard Deviation 40.7
|
44.5 mL/100g/min
Standard Deviation 18.1
|
|
Brain Blood Flow in the Anterior Cingulate With VNS Paired With Opioid Use Videos
2 minutes post-intervention
|
40.2 mL/100g/min
Standard Deviation 10.2
|
29.2 mL/100g/min
Standard Deviation 12.2
|
SECONDARY outcome
Timeframe: Baseline, 2 minutes post-interventionPopulation: Number analyzed in one or more rows differs from overall number analyzed because some data was not collected for technical reasons.
IL-6 is an inflammatory marker. Reduced levels of IL-6 correlate with better outcome.
Outcome measures
| Measure |
Active Non-invasive Vagal Nerve Stimulation (VNS)
n=10 Participants
Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.
Non invasive VN stimulation (nVNS): Stimulation of vagus nerve with active device.
Participants will be administered nVNS using the electroCore GammaCore-S non-invasive VNS device. The intensity of the stimulus will be adjusted by the user, to the maximum tolerable level to ensure nVNS without causing excessive pain, the burst frequency to 5 kHz, and the envelope frequency to 25 Hz.
The duration of delivery will be 2 minutes, and the beginning will coincide with initiation of acquisition of the HR-PET scan which will be 90 seconds in duration; following an additional 8 minutes, a second VNS delivery will be administered, in conjunction with which another scan will be obtained.
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
|
Sham Stimulation
n=5 Participants
Sham stimulation of vagus with opioid cues
Oxygen (15-O) Water: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus.
Sham Stimulation: Sham stimulation of vagus during opioid cue exposure. Each subject in the "SHAM" group will undergo the action of administering the intervention, but the device will be programmed such that the stimulation will not activate the vagus nerve.
|
|---|---|---|
|
Levels of Interleukin 6 (IL-6)
Baseline
|
1.4 pg/ml
Standard Deviation 0.8
|
4.0 pg/ml
Standard Deviation 3.1
|
|
Levels of Interleukin 6 (IL-6)
2 min post-intervention
|
2.6 pg/ml
Standard Deviation 2.6
|
3.9 pg/ml
Standard Deviation 3.1
|
Adverse Events
Active Non-invasive Vagal Nerve Stimulation (VNS)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Sham 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