Clinical trial NCT00901459: A Controlled Laboratory Study of the Effects on Cue-Induced Craving in Dependent Smokers
Official title: A Controlled Laboratory Study of the Effects on Cue-Induced Craving in Dependent Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nicotine Dependence
Keywords: Repetitive Transcranial Magnetic Stimulation
Cigarette Smoker
Cigarette Dependence
To block cue-elicited craving in dependent cigarette smokers
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2009-05-13
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Craving for Cigarettes After Smoking Cues Versus Neutral Cues Using a Repeated Measure Design.
timeFrame: Following exposure to in vivo cues
Secondary outcomes:
measure: Change in Craving for Cigarettes After Controlled Smoke Presentations.
timeFrame: After smoking a cigarette through the controlled puff volume apparatus during rTMS
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Center for Nicotine & Smoking Cessation Research
state: North Carolina
Study officials:
affiliation: Duke University
name: Jed E Rose, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Andrew D Krystal, M.D., M.S.
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Francis J McClernon, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rose JE, McClernon FJ, Froeliger B, Behm FM, Preud'homme X, Krystal AD. Repetitive transcranial magnetic stimulation of the superior frontal gyrus modulates craving for cigarettes. Biol Psychiatry. 2011 Oct 15;70(8):794-799. doi: 10.1016/j.biopsych.2011.05.031. Epub 2011 Jul 18.