Transcranial Magnetic Stimulation Used to Both Measure Cortical Excitability and Explore Methamphetamine Cue Craving

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT01685463
• Collaborator: National Institutes of Health (NIH) (NIH), National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 72
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Specific Primary Aims include:

Aim # 1. The investigators explore the feasibility of using the TMS to investigate the cortical excitability and to inhibit meth cue craving in meth dependent population. The investigators anticipate that meth elevates cortical excitability measured by motor threshold, causes changes of cortical silent period, and RC. The investigators also anticipate that paired pulse measures (short-interval intracortical inhibition, short-interval intracortical facilitation and long-interval intracortical inhibition) will be different from healthy control, which are more directly linked to glutamatergic cortical facilitation and GABAergic inhibition, respectively.

Aim # 2. Given the change of the cortical excitability in meth users, the investigators will use inhibiting TMS (1 Hz) over medial prefrontal cortex to study whether TMS can be used to reduce cue craving. The investigators hypothesize that repetitive TMS reduce meth cue craving in meth dependent population compared with sham rTMS.

Condition or Disease	Intervention/Treatment	Phase
Methamphetamine Dependence	Device: Transcranial Magnetic Stimulation; Device: Sham Transcranial Magnetic Stimulation	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Transcranial Magnetic Stimulation Used to Both Measure Cortical Excitability and Explore Methamphetamine Cue Craving
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Transcranial Magnetic Stimulation Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technology that can focally stimulate the brain of an awake individual. The brain stimulation techniques could theoretically improve the efficacy of smoking cessation.	Device: Transcranial Magnetic Stimulation; Active TMS:1 Hz, 100% motor threshold TMS for 15 minutes, total 900 pulses. Electrical stimulation instead.; Other Names: Magstim Rapid
Placebo Comparator: Sham Transcranial Magnetic Stimulation Sham-TMS procedures: After rTMS determination, participants were fitted with two electrodes on the scalp just below the hairline. Electrodes will be connected to an Epix VT Transcutaneous Electrical nerve stimulation device.	Device: Sham Transcranial Magnetic Stimulation; The electrical current of the sham system is titrated to a level matching participants' ratings of active TMS. The sham-TMS scalp discomfort will be matched to that of active TMS.; Other Names: Epix VT Transcutaneous Electrical Nerve Stimulation Device

Outcome Measures

Primary Outcome Measures

1. Cue Craving Rating [Change from Baseline in Craving rating 10 minutes after TMS]

   The subject is asked to rate craving with 0 mm being " no craving at all" and 100 mm representing "the most craving I have ever had".

Secondary Outcome Measures

1. Change in Baseline of Resting Motor Threshold [Baseline to 10 minutes after TMS]

   Resting motor threshold (RMT); on a scale of 0-100 with 100 being most power given to enact a motor response

2. Change in Cortical Silent Period [Baseline and 10 minutes after TMS]

   Cortical Silent Period is measured in seconds

3. Change Recruitment Curve (RC) Slope [Baseline and 10 minutes after TMS]

   Recruitment Curve (RC) Slope, measured at angle of slope

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Be volunteers who are dependent on meth and not currently seeking treatment. They must not have received substance abuse treatment within the previous 30 days.

2. Be male or female of any race or ethnic group, between the ages of 18 and 50 years.

3. Meet DSM IV criteria for meth dependence as determined by the MINI International Neuropsychiatric Interview (MINI).

4. Currently be using meth by smoked, oral, or intravenous routes of administration, used meth for a minimum of 2 years and a minimum of an average of 3 times a week in the 30 days prior to screening.

5. Be in stable mental and physical health.

6. If female, test non-pregnant and use adequate birth control. All female subjects will have urine pregnancy tests in all three phases of the study.

7. Be capable of providing written informed consent to participate in this study.

8. Be able to comply with protocol requirements and be likely to complete all study procedures.

9. Live within a 50 mile radius of our research program, have reliable transportation, and have a stable residence for at least the 30 days prior to starting the study.

10. Be willing to abstain from alcohol, marijuana and CNS acting prescription and OTC medications for the 2 week screening and hospitalization phases.

11. Have a positive urine for meth within 72 hours of admission to the hospital phase of the study and have at least one other positive urine for meth during the screening phase.

12. Be right-handed.

Exclusion Criteria:

1. Have current dependence, defined by DSM IV criteria, on any psychoactive substances other than meth, nicotine, or caffeine.

2. Have a history and/or test positive for significant hepatic, renal, endocrine, cardiac, or inflammatory diseases, as well as stroke, seizures, migraine, serious head trauma, or other neurological disorders that might interfere with stability during the study or the acquisition of accurate fMRI scans.

3. If female, have intentions to become pregnant during the study.

4. Have been required by the courts to obtain treatment for meth or some other substance dependence.

5. Be seeking treatment for meth or other substance dependence.

6. Have a medical history or condition considered by the investigators to place the subject at increased risk (implanted ferrous materials or devices) or to decrease the likelihood of study completion.

7. Be anticipating elective surgery or hospitalization within 8 weeks of signing the informed consent agreement.

8. Be on medications in the last 30 days that may alter CNS function or alter fMRI results. Examples of such medications include but are not limited to the following: psychotropics, CNS active anti-hypertensives, steroids, anticonvulsants, antihistamines and CNS OTCs.

9. Have a life time history of major Axis I disorders such as: BPAD, Schizophrenia, PTSD, or Dementia, or have a current history of Major Depression or suicide attempt within 12 months

10. Have a self report of >21 standard alcohol drinks per week in any week in the 30 days prior to screening or a Carbohydrate Deficient Transferrin >3.0%.

11. Be unwilling to use a patch and cease smoking cigarettes for the eight days in the hospital.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina
• National Institutes of Health (NIH)
• National Institute on Drug Abuse (NIDA)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Barr MS, Farzan F, Wing VC, George TP, Fitzgerald PB, Daskalakis ZJ. Repetitive transcranial magnetic stimulation and drug addiction. Int Rev Psychiatry. 2011 Oct;23(5):454-66. doi: 10.3109/09540261.2011.618827. Review.
• Feil J, Zangen A. Brain stimulation in the study and treatment of addiction. Neurosci Biobehav Rev. 2010 Mar;34(4):559-74. doi: 10.1016/j.neubiorev.2009.11.006. Epub 2009 Nov 13. Review.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT01685463
• Other Study ID Numbers: NIH/NIDA P20 DA022658; P20DA022658
• First Posted: Sep 14, 2012
• Last Update Posted: Apr 1, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by Medical University of South Carolina: methamphetamine, craving, TMS, cortical excitability, prefrontal cortex

Study Results

Participant Flow

Arm/Group Title	Transcranial Magnetic Stimulation	Sham Transcranial Magnetic Stimulation
Arm/Group Description	Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technology that can focally stimulate the brain of an awake individual. The brain stimulation techniques could theoretically improve the efficacy of smoking cessation. Transcranial Magnetic Stimulation: Active TMS:1 Hz, 100% motor threshold TMS for 15 minutes, total 900 pulses. Electrical stimulation instead.	Sham-TMS procedures: After rTMS determination, participants were fitted with two electrodes on the scalp just below the hairline. Electrodes will be connected to an Epix VT Transcutaneous Electrical nerve stimulation device. Sham Transcranial Magnetic Stimulation: The electrical current of the sham system is titrated to a level matching participants' ratings of active TMS. The sham-TMS scalp discomfort will be matched to that of active TMS.
Period Title: Overall Study
STARTED	10	8
COMPLETED	10	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Transcranial Magnetic Stimulation	Sham Transcranial Magnetic Stimulation	Total
Arm/Group Description	Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technology that can focally stimulate the brain of an awake individual. The brain stimulation techniques could theoretically improve the efficacy of smoking cessation. Transcranial Magnetic Stimulation: Active TMS:1 Hz, 100% motor threshold TMS for 15 minutes, total 900 pulses. Electrical stimulation instead.	Sham-TMS procedures: After rTMS determination, participants were fitted with two electrodes on the scalp just below the hairline. Electrodes will be connected to an Epix VT Transcutaneous Electrical nerve stimulation device. Sham Transcranial Magnetic Stimulation: The electrical current of the sham system is titrated to a level matching participants' ratings of active TMS. The sham-TMS scalp discomfort will be matched to that of active TMS.	Total of all reporting groups
Overall Participants	10	8	18
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	8 100%	18 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.7 (10.6)	32.5 (14.4)	33.7 (11.2)
Sex: Female, Male (Count of Participants)
Female	6 60%	7 87.5%	13 72.2%
Male	4 40%	1 12.5%	5 27.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	10 100%	8 100%	18 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%	8 100%	18 100%

Outcome Measures

1. Primary Outcome

Title	Cue Craving Rating
Description	The subject is asked to rate craving with 0 mm being " no craving at all" and 100 mm representing "the most craving I have ever had".
Time Frame	Change from Baseline in Craving rating 10 minutes after TMS

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcranial Magnetic Stimulation	Sham Transcranial Magnetic Stimulation
Arm/Group Description	Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technology that can focally stimulate the brain of an awake individual. The brain stimulation techniques could theoretically improve the efficacy of smoking cessation. Transcranial Magnetic Stimulation: Active TMS:1 Hz, 100% motor threshold TMS for 15 minutes, total 900 pulses. Electrical stimulation instead.	Sham-TMS procedures: After rTMS determination, participants were fitted with two electrodes on the scalp just below the hairline. Electrodes will be connected to an Epix VT Transcutaneous Electrical nerve stimulation device. Sham Transcranial Magnetic Stimulation: The electrical current of the sham system is titrated to a level matching participants' ratings of active TMS. The sham-TMS scalp discomfort will be matched to that of active TMS.
Measure Participants	10	8
Mean (Standard Error) [scores on a scale]	9.36 (0.75)	7.92 (0.85)

2. Secondary Outcome

Title	Change in Baseline of Resting Motor Threshold
Description	Resting motor threshold (RMT); on a scale of 0-100 with 100 being most power given to enact a motor response
Time Frame	Baseline to 10 minutes after TMS

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcranial Magnetic Stimulation	Sham Transcranial Magnetic Stimulation
Arm/Group Description	Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technology that can focally stimulate the brain of an awake individual. The brain stimulation techniques could theoretically improve the efficacy of smoking cessation. Transcranial Magnetic Stimulation: Active TMS:1 Hz, 100% motor threshold TMS for 15 minutes, total 900 pulses. Electrical stimulation instead.	Sham-TMS procedures: After rTMS determination, participants were fitted with two electrodes on the scalp just below the hairline. Electrodes will be connected to an Epix VT Transcutaneous Electrical nerve stimulation device. Sham Transcranial Magnetic Stimulation: The electrical current of the sham system is titrated to a level matching participants' ratings of active TMS. The sham-TMS scalp discomfort will be matched to that of active TMS.
Measure Participants	10	8
Mean (Standard Deviation) [units on a scale]	47.3 (16.2)	47.2 (13.5)

3. Secondary Outcome

Title	Change in Cortical Silent Period
Description	Cortical Silent Period is measured in seconds
Time Frame	Baseline and 10 minutes after TMS

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcranial Magnetic Stimulation	Sham Transcranial Magnetic Stimulation
Arm/Group Description	Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technology that can focally stimulate the brain of an awake individual. The brain stimulation techniques could theoretically improve the efficacy of smoking cessation. Transcranial Magnetic Stimulation: Active TMS:1 Hz, 100% motor threshold TMS for 15 minutes, total 900 pulses. Electrical stimulation instead.	Sham-TMS procedures: After rTMS determination, participants were fitted with two electrodes on the scalp just below the hairline. Electrodes will be connected to an Epix VT Transcutaneous Electrical nerve stimulation device. Sham Transcranial Magnetic Stimulation: The electrical current of the sham system is titrated to a level matching participants' ratings of active TMS. The sham-TMS scalp discomfort will be matched to that of active TMS.
Measure Participants	10	8
Mean (Standard Deviation) [seconds]	0.163 (.053)	.139 (.036)

4. Secondary Outcome

Title	Change Recruitment Curve (RC) Slope
Description	Recruitment Curve (RC) Slope, measured at angle of slope
Time Frame	Baseline and 10 minutes after TMS

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcranial Magnetic Stimulation	Sham Transcranial Magnetic Stimulation
Arm/Group Description	Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technology that can focally stimulate the brain of an awake individual. The brain stimulation techniques could theoretically improve the efficacy of smoking cessation. Transcranial Magnetic Stimulation: Active TMS:1 Hz, 100% motor threshold TMS for 15 minutes, total 900 pulses. Electrical stimulation instead.	Sham-TMS procedures: After rTMS determination, participants were fitted with two electrodes on the scalp just below the hairline. Electrodes will be connected to an Epix VT Transcutaneous Electrical nerve stimulation device. Sham Transcranial Magnetic Stimulation: The electrical current of the sham system is titrated to a level matching participants' ratings of active TMS. The sham-TMS scalp discomfort will be matched to that of active TMS.
Measure Participants	10	8
Mean (Standard Deviation) [ratio]	.272 (.196)	.135 (.073)

Adverse Events

Arm/Group Title	Transcranial Magnetic Stimulation		Sham Transcranial Magnetic Stimulation
Arm/Group Description	Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technology that can focally stimulate the brain of an awake individual. The brain stimulation techniques could theoretically improve the efficacy of smoking cessation. Transcranial Magnetic Stimulation: Active TMS:1 Hz, 100% motor threshold TMS for 15 minutes, total 900 pulses. Electrical stimulation instead.		Sham-TMS procedures: After rTMS determination, participants were fitted with two electrodes on the scalp just below the hairline. Electrodes will be connected to an Epix VT Transcutaneous Electrical nerve stimulation device. Sham Transcranial Magnetic Stimulation: The electrical current of the sham system is titrated to a level matching participants' ratings of active TMS. The sham-TMS scalp discomfort will be matched to that of active TMS.
All Cause Mortality
	Transcranial Magnetic Stimulation		Sham Transcranial Magnetic Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/8 (0%)
Serious Adverse Events
	Transcranial Magnetic Stimulation		Sham Transcranial Magnetic Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Transcranial Magnetic Stimulation		Sham Transcranial Magnetic Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.