Nicotine Dependence
Conditions
Keywords
Repetitive Transcranial Magnetic Stimulation, Cigarette Smoker, Cigarette Dependence, To block cue-elicited craving in dependent cigarette smokers
Brief summary
The purpose of this study is to investigate the use of repetitive transcranial magnetic stimulation (rTMS) to block craving for cigarettes in smokers. rTMS is an investigational procedure, where a device called a stimulator provides electricity to a device that creates a magnetic field. This device is placed against the scalp in the front of the head so that the magnetic field is focused on an area of the brain that is thought to be involved in craving for cigarettes. rTMS is an investigational procedure so therefore being tested in research studies and is not approved by the U.S. Food and Drug Administration (FDA). Changes in magnetic fields during rTMS administration change electrical currents which may affect brain activity and function.
Detailed description
The goal of this study is to evaluate the effects of rTMS on cue-induced craving in dependent smokers. We hypothesize that low frequency rTMS over the SFG will block cue-induced craving. In order to test this hypothesis, subjects will undergo three conditions: 1. active condition: low frequency rTMS was administered over the superior frontal gyrus (SFG) during the presentation of smoking and control cues 2. location control condition: low frequency rTMS was administered over motor cortex (MC) during the presentation of smoking and control cues 3. frequency control condition: high frequency rTMS was administered over the SFG during the presentation of smoking and control cues
Interventions
DEVICEActive rTMS Condition
Low frequency rTMS (90% Motor Threshold at 1 HZ) will be administered over the superior frontal gyrus (SFG) during the presentation of smoking and control cues.
DEVICErTMS Location Control Condition
Low frequency rTMS (90% Motor Threshold at 1 HZ) will be administered over the motor cortex (MC) during the presentation of smoking and control cues.
DEVICErTMS Frequency Control Condition
High frequency rTMS (90% Motor Threshold at 10 HZ) will be administered over the superior frontal gyrus (SFG) during the presentation of smoking and control cues.
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. 18 to 50 years of age; 2. dependent smoker of \> 10 cigarettes per day of cigarettes yielding \>0.5mg nicotine (by Federal Trade Commission rated yields); 3. have smoked cigarettes for at least three cumulative years; 4. an afternoon carbon monoxide reading of at least 10ppm; 5. be in general good health based on physical examination, EKG, serum chemistries, CBC, and urinalysis and 6. show evidence of greater craving following exposure to in vivo smoking versus control cues
Exclusion criteria
1. Individuals with a clinically defined neurological disorder or insult including, but not limited to, any condition likely to be associated with increased intracranial pressure; 2. space occupying brain lesion; 3. any history of seizure EXCEPT those therapeutically induced by ECT (Electro Convulsive Therapy); 4. history of cerebrovascular accident; 5. transient ischemic attack within two years; 6. cerebral aneurysm; 7. dementia; 8. Parkinson's disease; 9. Huntington's chorea; 10. multiple sclerosis; 11. current lung disease or lung disorder; 12. hypertension (systolic \>140 mmHg, diastolic \> 90 mmHg); 13. hypotension (\< 90 mmHg, diastolic \< 60 mmHg); 14. coronary artery disease; 15. cardiac rhythm disorder; 16. impaired hepatic or renal function (based on documented diagnosis or abnormal chemistries) except gallstones or kidney stones; 17. other major medical or psychiatric condition; 18. use of any concurrent hypertensive, psychiatric, or psychoactive medication; 19. any concurrent medication that lowers seizure threshold; 20. smokeless tobacco, pipe, or cigar use in the past 30 days; 21. nicotine replacement therapy, or other smoking cessation therapy within the past 30 days; 22. increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or history of significant head trauma with loss of consciousness for \> 5 minutes; 23. ECT treatment within 3 months prior to screening visit; 24. failure to respond to ECT treatment (i.e., consistent with ATHF level 2 or higher); 25. a true positive response to any question on the Transcranial Magnetic Stimulation Adult Safety Screen questionnaire; 26. history of treatment with rTMS therapy for any disorder; 27. use of any investigational drug within 30 days of the screening visit; 28. history of treatment with Vagus Nerve Stimulation; 29. use of any medication(s) with active CNS properties within 1 week of the screening visit; 30. cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease; intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed; 31. known or suspected pregnancy; 32. positive urine drug screen or reported drug abuse in the past 30 days; 33. clinically significant laboratory abnormality, in the opinion of the investigator or study physician; 34. women who are breast-feeding; women of child-bearing potential not using a medically accepted form of contraception when engaging in sexual intercourse; 35. current chronic pain or other pain condition that interferes with daily activities or requires use of prescription medication; 36. claustrophobia or abnormal fear of cramped or confined space; 37. Individuals where a motor threshold response is not elicited with stimulation at or below 80% of maximum output; 38. active ulcer within the past 30 days; 39. frequent migraines (great than four in the past 30 days); 40. Females who score greater than or equal to 13 and males who score greater than or equal to 15 on the AUDIT (Alcohol Use Disorders Identification Test)will be excluded from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Craving for Cigarettes After Smoking Cues Versus Neutral Cues Using a Repeated Measure Design. | Following exposure to in vivo cues | Cigarette craving was assessed orally during each rTMS Session, before and after each stimulus presentation and cigarette smoking with a brief version of the Shiffman-Jarvik questionnaire (14), which contained items assessing cigarette craving using the following subscale: CRAVING (urges to smoke, miss a cigarette, and crave cigarettes), MOOD (calm, tense, and irritable), AROUSAL (wide awake, able to concentrate), and HUNGER (feel hungry). The scale for the Shiffman-Jarvik questionnaire is a Likert item scale with measurements 1-Not at All; 2-Very Little; 3-A Little; 4-Moderately; 5- A Lot; 6-Quite A Lot and 7-Extremely. The change in craving for cigarettes after smoking cues versus neutral cues using the parenthetical items listed above with the subscale CRAVING were used to determine the primary outcome. A negative value represents a decrease in reported cigarette craving. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Craving for Cigarettes After Controlled Smoke Presentations. | After smoking a cigarette through the controlled puff volume apparatus during rTMS | Craving reduction was assessed orally by an item on the cigarette evaluation questionnaire (Did it immediately reduce your craving for cigarettes?) after smoking presentations through the controlled puff volume apparatus. |
Countries
United States
Participant flow
Recruitment details
The first participant was consented on 5/12/2009 and the final participant on 6/22/2010 at the Duke Center for Nicotine and Smoking Cessation Research. During the recruitment phase of the study 148 potential subjects were consented and 7 read the consent form and chose not to participate.
Pre-assignment details
Of the 148 participants that were consented for this study only 21 subjects met study criteria the others were excluded from participation for the following reasons: 70-Did Not Meet Inclusion Criteria 6-Lab Results 6-Lost to Contact 26-Medical 14-Met exclusion criteria 3-Refused to participate 2-Unable To Meet Study Requirements
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Active:
rTMS Dosing: 90% MT (Motor Threshold) 1 Hz rTMS Location: Superior Frontal Gyrus
Location Control:
rTMS Dosing: 90% MT (Motor Threshold) 1 Hz rTMS Location: Motor Cortex
Frequency Control:
rTMS Dosing: 90% MT (Motor Threshold) 10 Hz rTNS Location: Superior Frontal Gyrus | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age Continuous | 39.9 years STANDARD_DEVIATION 8.88 |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Change in Craving for Cigarettes After Smoking Cues Versus Neutral Cues Using a Repeated Measure Design.
Cigarette craving was assessed orally during each rTMS Session, before and after each stimulus presentation and cigarette smoking with a brief version of the Shiffman-Jarvik questionnaire (14), which contained items assessing cigarette craving using the following subscale: CRAVING (urges to smoke, miss a cigarette, and crave cigarettes), MOOD (calm, tense, and irritable), AROUSAL (wide awake, able to concentrate), and HUNGER (feel hungry). The scale for the Shiffman-Jarvik questionnaire is a Likert item scale with measurements 1-Not at All; 2-Very Little; 3-A Little; 4-Moderately; 5- A Lot; 6-Quite A Lot and 7-Extremely. The change in craving for cigarettes after smoking cues versus neutral cues using the parenthetical items listed above with the subscale CRAVING were used to determine the primary outcome. A negative value represents a decrease in reported cigarette craving.
Time frame: Following exposure to in vivo cues
Population: A repeated measures design exposed participants to three different rTMS conditions over 3 separate visits, with order counterbalanced using latin square design.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Craving for Cigarettes After Smoking Cues Versus Neutral Cues Using a Repeated Measure Design. | -.18 units on a scale | Standard Error 0.95 |
| Location Control | Change in Craving for Cigarettes After Smoking Cues Versus Neutral Cues Using a Repeated Measure Design. | .12 units on a scale | Standard Error 1.3 |
| Frequency Control | Change in Craving for Cigarettes After Smoking Cues Versus Neutral Cues Using a Repeated Measure Design. | 1.29 units on a scale | Standard Error 1.52 |
Comparison: A pairwise t-test was performed to contrast the active rTMS condition with the frequency control condition.p-value: 0.01495% CI: [0.51, 2.43]t-test, 2 sided
Comparison: A pairwise t-test was performed to contrast the active rTMS condition with the location control condition.p-value: 0.4995% CI: [-0.64, 1.22]t-test, 2 sided
Comparison: A pairwise t-test was performed to contrast the location control rTMS condition with the frequency control condition.p-value: 0.0995% CI: [0.52, 1.39]t-test, 2 sided
Secondary
Change in Craving for Cigarettes After Controlled Smoke Presentations.
Craving reduction was assessed orally by an item on the cigarette evaluation questionnaire (Did it immediately reduce your craving for cigarettes?) after smoking presentations through the controlled puff volume apparatus.
Time frame: After smoking a cigarette through the controlled puff volume apparatus during rTMS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Craving for Cigarettes After Controlled Smoke Presentations. | -.18 units on a scale | Standard Deviation 0.95 |
| Location Control | Change in Craving for Cigarettes After Controlled Smoke Presentations. | .12 units on a scale | Standard Deviation 1.3 |
| Frequency Control | Change in Craving for Cigarettes After Controlled Smoke Presentations. | 1.29 units on a scale | Standard Deviation 1.52 |