Identifying Electrophysiological Targets for Transcranial Magnetic Stimulation in Cocaine Use Disorder

Cocaine Use Disorder Clinical Trial

Official title:

Identifying Electrophysiological Targets for Transcranial Magnetic Stimulation in Cocaine Use Disorder

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05986578
• Other study ID #: HSC-MS-21-0813 (Main study)
• Secondary ID: K01DA058765
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: June 30, 2028

Study information

• Verified date: May 2024
• Source: The University of Texas Health Science Center, Houston
• Contact: Heather Webber, PhD
• Phone: 713-486-2723
• Email: Heather.E.Webber[@]uth.tmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess effects of intermittent theta burst stimulation (iTBS) to left dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) compared to sham on electrophysiological indices of reward sensitivity and motivated attention in adults with cocaine use disorder.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 75
• Est. completion date: June 30, 2028
• Est. primary completion date: June 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• non-treatment-seeking adults
• meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for current cocaine use disorder of at least moderate severity (= 4 symptoms)
• have at least 1 positive urine Benzoylecgonine (BE) specimen (= 300 ng/mL) during intake
• be able to understand the consent form and provide written informed consent
• be able to provide the following verifiable information for a minimum of 2 contact persons: full legal name,email address, local mailing address, and as applicable, home, work, and cell phone numbers

Exclusion Criteria:

• current DSM-5 diagnosis for substance use disorder (of at least moderate severity) other than cocaine, marijuana, or nicotine
• in the opinion of the principal investigator (PI), the presence of any medical, neurological, psychiatric, or physical condition, disease, or illness that, may: (a) compromise interfere, limit, effect or reduce the subject's ability to complete the study; or (b) adversely impact the safety of the subject or the integrity of the data
• has current or recent (within 3 months of potential enrollment) suicidal ideation, suicidal behavior, homicidal ideation or a homicidal plan sufficient to raise subject

safety concerns based on the following assessments according to the PI:

1. Structured Clinical Interview for DSM-5 (SCID-5)

2. Columbia Suicide Severity Rating Scale (C-SSRS) Screener - Answers YES to Questions 3, 4, 5, or 6

3. Assault & Homicidal Danger Assessment Tool - Key to Danger > 1

• medical implants contraindicating TMS (i.e., aneurysm clips or coils, stents, implanted stimulators, implanted vagus nerve or deep brain stimulators, implanted electrical devices such as pacemakers or medication pumps electrodes for monitoring brain activity, cochlear implants for hearing, any magnetic implants, bullet fragments, any other metal device or object implanted in your body closer than 30 cm from the coil)
• history of brain surgery
• history of an intracranial lesion or any medical or neurological diagnosis/condition associated with increased intracranial pressure (i.e., Idiopathic Intracranial Hypertension/Pseudotumor Cerebri) OR any of the following symptoms within 30 days of enrollment: headaches > 15 days/month, loss of vision or decreased vision
• moderate-to-severe heart disease
• history of stroke
• is taking any antidepressant or antipsychotic medication at a dose above the maximum recommended dose or at a dose deemed to be potentially unsafe according to the PI; has taken any of the following medications, which are known to increase the risk of seizures, within 1 week of study enrollment; or does not agree to abstain from taking

the following medications during study participation:

1. clozapine137

2. chlorpromazine137

3. bupropion

4. clomipramine hydrochloride

5. amoxapine

6. maprotiline hydrochloride

7. diphenhydramine

8. stimulants other than cocaine including the following:

1. Dextroamphetamine and amphetamine

2. Dextroamphetamine

3. Lisdexamfetamine dimesylate

4. Methamphetamine

5. Methylphenidate

9. tramadol

10. isoniazid

• having conditions of probation or parole requiring reports of drug use to officers of the court
• personal history of epilepsy or seizure disorder and/or family history including a first-degree relative
• serious head injury with loss of consciousness
• impending incarceration
• pregnant or nursing for female patients
• inability to read, write, or speak English
• for adolescent aged participants (18-21 only): any risk factor for neurocardiogenic syncope (history of syncope/presyncope related to noxious stimuli, anxiety, micturition, or posture)
• hair style that is incompatible with EEG nets

Related Conditions & MeSH terms

• Cocaine Use Disorder

Intervention

Device:
• TMS to dmPFC
TMS will be delivered with a MagVenture Mag Pro R30 with the Cool-B70 A/P coil with active liquid cooling and active/sham sides. For dmPFC, approximately 25% of the nasion-inion distance or Talairah coordinates X 0 Y+60 Z+60 will be measured. The first session will begin with the acquisition of the resting motor threshold (rMT) on the contralateral hand. iTBS (triplet 50 Hz bursts, repeated at 5 Hz, 2 sec on and 8 sec off; 600 pulses per session) will be delivered at 110% of the rMT and will last ~3 minutes. The stimulation will start at a lower percentage and ramp up over time to acclimate participant to the feeling of stimulation. The intensity will be lowered in participant cannot tolerate the stimulation. Each participant will receive 3 sessions per visit with a 15-20 minute interval between sessions to increase the likelihood of detecting acute effects.
• TMS to dlPFC
TMS will be delivered with a MagVenture Mag Pro R30 with the Cool-B70 A/P coil with active liquid cooling and active/sham sides. For dlPFC, position F3 will be measured, using probabilistic EEG placement. The first session will begin with the acquisition of the resting motor threshold on the contralateral hand. iTBS (triplet 50 Hz bursts, repeated at 5 Hz, 2 sec on and 8 sec off; 600 pulses per session) will be delivered at 110% of the rMT and will last 3 minutes. The stimulation will start at a lower percentage and ramp up over time to acclimate participant to the feeling of stimulation. The intensity will be lowered in participant cannot tolerate the stimulation. Each participant will receive 3 sessions per visit with a 15-20 minute interval between sessions to increase the likelihood of detecting acute effects.
• Sham iTBS
Sham TMS will be delivered with the sham side of the MagVenture Cool B70 A/P coil. The software will be pre-programmed by a staff member that will not be involved in data analysis or collection for blinding purposes. The sham stimulation will match the number of pulses and length of time as the active condition and each participant will receive 3 sessions with a 15-20 min interval between sessions.

Locations

Country	Name	City	State
United States	The University of Texas Health Science Center at Houston	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the amplitude of the Reward Positivity (RewP) component in microvolts in response to feedback on the Doors Task	The Doors Task will be used to elicit the RewP component, representing reward sensitivity. The task is a guessing game, where participants guess which door contains a reward behind it. After selecting a door, the participants are notified if they found the prize by a green arrow pointing up or if they did not find the prize by a red arrow pointing down.	Baseline(before iTBS session),immediately after iTBS session
Primary	Change in the amplitude of the Late Positive Potential (LPP) in microvolts in response to visual stimuli on the Picture Viewing Task.	The Picture Viewing Task will be used to elicit the LPP, reflecting the motivational salience of a stimulus. During this task, participants are asked to view a slide show of images including pleasant, unpleasant, neutral, and cocaine-related images.	Baseline(before iTBS session),immediately after iTBS session
Secondary	Change in craving as assessed by the Minnesota Cocaine Craving Scale (MCCS)	The intensity of craving score will be used, scored from 1(none at all) to 10 (a great deal).	Baseline(before iTBS session),immediately after iTBS session
Secondary	Change in pain as assessed by the Visual Analogue Scale	This is scored from 1(no pain) to 10 (worst pain)	Baseline(before iTBS session),immediately after iTBS session
Secondary	Change in cognitive function as assessed by the The Montreal Cognitive Assessment (MoCA)	Total score on the Montreal Cognitive Assessment (MoCA) range from 0 to 30, with a higher score indicating a better outcome.	Baseline(before iTBS session),immediately after iTBS session
Secondary	Change in behavioral reward learning as assessed by the Pavlovian Go/No-Go task	In the first "learning" phase, participants learn whether to press a button or withhold a response to receive a monetary reward or avoid a loss. In the second "transfer" phase, participants perform a forced choice task, where each of the predictive cues in the learning phase are paired with each other. Participants must select the "most rewarding" cue.	Baseline(before iTBS session),immediately after iTBS session
Secondary	Change in Anhedonia as assessed by the Snaith Hamilton Pleasure Scale (SHAPS)	This is a 14 item questionnaire. 9 of the questions are scored from 0(strongly disagree) to 3( strongly agree) and the rest are reverse coded with answer choices as follows: definitely agree, agree, disagree, and strongly disagree. Final scores range from 0-14 and higher score indicates worse outcome.	Baseline(before iTBS session),immediately after iTBS session