Alcohol Use Disorder
Conditions
Keywords
Transcranial magnetic stimulation (TMS)
Brief summary
The study will examine the effects of two continuous theta burst stimulation (cTBS) sessions (given in a single day) on resting state functional MRI (fMRI), alcohol cue related attentional bias and alcohol craving in patients with alcohol use disorder (AUD).
Detailed description
Although pharmacotherapy and behavioral treatments have been approved for AUD, their effects sizes are modest. Noninvasive neuromodulation like Transcranial magnetic stimulation (TMS) can offer an alternative treatment option for AUD. TMS is a method of noninvasive neuromodulation that utilizes a magnetic field to focal electrical current in the brain. When these electrical currents are focused on specific brain regions, pertinent to the neurobiology of AUD it leads to modulation of behavior and plausibly decrease in alcohol craving and use. Previous TMS studies have used heterogenous parameters, including frequencies ranging from 1 Hz to 20 Hz. Regions targeted by these studies encompassed ventromedial prefrontal cortex, left dorsolateral prefrontal cortex (left dlPFC) and right dorsolateral prefrontal cortex. Two studies used a TMS paradigm with greater efficiency than other routine TMS paradigms, called continuous theta burst stimulation. These studies delivered 3600 pulses of cTBS to the left frontal pole/ventromedial prefrontal cortex and showed significant reduction in alcohol cue reactivity and corroborative changes in both resting state and task based functional connectivity. Of these two studies, one was notable in comparing active cTBS (3600 pulses per session, one session every day for ten days over two weeks) versus sham cTBS. A deep TMS (dTMS) study that compared dTMS (15 sessions, five sessions every week for three weeks) to sham dTMS using an H7 coil (targeting medial prefrontal and anterior cingulate cortices). This study showed decreased craving after treatment and percentage of heavy drinking days in the active versus sham control group. Active dTMS was associated with decreased resting-state functional connectivity of the dorsal anterior cingulate cortex with the caudate nucleus and decreased connectivity of the medial prefrontal cortex to the subgenual anterior cingulate cortex. No study has done multiple sessions of cTBS in a single day. In addition, no study has previously delivered cTBS to the left dlPFC, to modulate alcohol craving and alcohol cue based attentional bias.
Interventions
DEVICEActive cTBS
Two cTBS sessions (each session delivering 3600 pulses) separated by 50 minutes
DEVICESham cTBS
Two sham cTBS sessions (sham mimics the experimental session but does not deliver any electricity to the brain) separated by 50 minutes
Sponsors
National Cancer Institute (NCI)
Gopalkumar Rakesh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Using the MagVenture A/P coil
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
. * Patients seen at a clinic within the University of Kentucky Healthcare * 21-60 years of age * male or female gender * Able to read, understand and communicate in English * willing to adhere to the general rules of the UK Healthcare * Must fulfill criteria for moderate alcohol use disorder.
Exclusion criteria
* Positive pregnancy test for females * traumatic brain injury, history of seizure disorder, history of or current diagnosis of schizophrenia * intracranial metal shrapnel * previous adverse effect with TMS * sub-threshold consistency while performing behavioral tasks * failure to show baseline attentional bias to alcohol versus neutral cues.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Penn Alcohol Craving Scale | Before and after two cTBS sessions, approximately 2 hours | Craving measured using the Penn alcohol craving scale (PACS) that has five items and is rated on a scale of 1 to 6. Minimum score is 1 and maximum score is 30. Higher score equates to increased craving |
| Change in Alcohol Cue Attentional Bias | Before and after two cTBS sessions, approximately 2 hours | Fixation time on alcohol cues measured using an eye tracker in milliseconds. Higher score indicates greater attentional bias. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resting State Functional Connectivity | Before and after two cTBS sessions, approximately 2 hours | Number of participants with resting state functional connectivity scans acquired before and after cTBS and sham cTBS |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active cTBS and Sham cTBS There is only one arm in this study and all participants in this arm will receive 2 interventions: active and sham cTBS in a within subject blinded fashion. They will first receive active cTBS and then sham cTBS, separated by four weeks to minimize carryover effects.
Active cTBS: Two cTBS sessions (each session delivering 3600 pulses) separated by 50 minutes
Sham cTBS: Two sham cTBS sessions (sham mimics the experimental session but does not deliver any electricity to the brain) separated by 50 minutes | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Active cTBS and Sham cTBS |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 41 years STANDARD_DEVIATION 11.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Change in Alcohol Cue Attentional Bias
Fixation time on alcohol cues measured using an eye tracker in milliseconds. Higher score indicates greater attentional bias.
Time frame: Before and after two cTBS sessions, approximately 2 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| cTBS and Sham cTBS | Change in Alcohol Cue Attentional Bias | Baseline_cTBS | 294.92 milliseconds | Standard Deviation 667.18 |
| cTBS and Sham cTBS | Change in Alcohol Cue Attentional Bias | After second session_cTBS | 459.60 milliseconds | Standard Deviation 1618.57 |
| cTBS and Sham cTBS | Change in Alcohol Cue Attentional Bias | Baseline_sham cTBS | 355.3 milliseconds | Standard Deviation 659.06 |
| cTBS and Sham cTBS | Change in Alcohol Cue Attentional Bias | After second session_sham cTBS | 666.30 milliseconds | Standard Deviation 1592.36 |
Primary
Change in Penn Alcohol Craving Scale
Craving measured using the Penn alcohol craving scale (PACS) that has five items and is rated on a scale of 1 to 6. Minimum score is 1 and maximum score is 30. Higher score equates to increased craving
Time frame: Before and after two cTBS sessions, approximately 2 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| cTBS and Sham cTBS | Change in Penn Alcohol Craving Scale | Baseline_cTBS | 11.50 units on a scale | Standard Deviation 9.68 |
| cTBS and Sham cTBS | Change in Penn Alcohol Craving Scale | After second session_cTBS | 11.75 units on a scale | Standard Deviation 9.43 |
| cTBS and Sham cTBS | Change in Penn Alcohol Craving Scale | Baseline_sham cTBS | 8.25 units on a scale | Standard Deviation 5.44 |
| cTBS and Sham cTBS | Change in Penn Alcohol Craving Scale | After second session_sham cTBS | 7.25 units on a scale | Standard Deviation 6.7 |
Secondary
Resting State Functional Connectivity
Number of participants with resting state functional connectivity scans acquired before and after cTBS and sham cTBS
Time frame: Before and after two cTBS sessions, approximately 2 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| cTBS and Sham cTBS | Resting State Functional Connectivity | 4 Participants |