Nicotine Addiction, Panic Attack
Conditions
Brief summary
The purpose of the current study is to evaluate the efficacy of d-cycloserine in augmenting treatment of smoking cessation for individuals with panic attacks. The investigators hypothesize that individuals receiving DCS (versus those receiving placebo) will evidence greater smoking abstinence rates and decreased panic symptoms after receiving a combined CBT-based treatment for smokers with panic attacks.
Interventions
DRUGd-cycloserine
d-cycloserine is a medication thought to be associated with fear extinction.
DRUGPill Placebo
DRUGNicotine replacement therapy
All participants will receive Nicoderm CQ®, 24-hour transdermal nicotine patches and will be educated about the use of the patch at the session immediately prior to quit date. They will be instructed to apply one patch daily, beginning on quit date (week 5). Participants will use the 3-step tapering Nicoderm process (21-mg, 14-mg, and 7-mg). This regimen has been used in previous trials with a similar formulation of the patch (Fiore, 2000). A meta-analysis found no differences in outcome between 16- or 24-hour patches (Fiore et al., 1994). Participants who continue to smoke or lapse after quit day will not be instructed to discontinue the patch until their smoking level reaches 4 cigarettes/day for 4 days. Smokers who lapse during treatment will be encouraged to set a new quit date and continue their cessation attempt.
BEHAVIORALPanic and Smoking Reduction Treatment
PSRT incorporates elements of standard smoking cessation treatment (i.e., counseling plus NRT) with procedures for reducing panic and enhancing tolerance to withdrawal sensations. Written therapist and patient manuals will be used and followed at all times to ensure standardized delivery of the treatment. Interventions that uniquely focus on addressing panic, fears and intolerance of anxiety, bodily-related sensations, and affect-relevant withdrawal symptoms include: (1) interoceptive exposure; (2) corrective information about anxiety and cognitive interventions designed to teach patients alternatives to catastrophic misinterpretations of the sensations and their feared consequences; and (3) situational exposure.
Sponsors
University of Texas at Austin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female patients ages 18-65 capable of providing informed consent * Willing and able to provide informed consent, attend all study visits and comply with the protocol * Daily smoker for at least one year * Currently smoke an average of at least 8 cigarettes per day * Report a motivation to quit smoking in the next month of at least 5 on a 10-point scale * Evidence of panic attack within the past year and endorsement of smoking as an emotion regulation strategy (i.e., score at least a 78 on the SAEQ).
Exclusion criteria
* Subjects who do not use smoking as an emotion regulation strategy * Current diagnosis of a psychotic, eating, developmental or bipolar disorder * Significant suicide risk as determined by structured interview * Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months). * Psychoactive substance abuse or dependence (excluding nicotine dependence) within the past 6 months * Current use of isoniazid or ethionamide compounds * A history of significant medical condition and/or be deemed as currently unhealthy in the context of a complete physical examination * Limited mental competency and the inability to give informed, voluntary, written consent to participate * Current use of any pharmacotherapy or psychotherapy for smoking cessation not provided by the researchers during the quit attempt * Concurrent psychotherapy initiated within three months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of anxiety or mood disorder other than general supportive therapy initiated at least 3 months prior to the study * Use of other tobacco products * Plans to move outside of the immediate area in the next six months * Insufficient command of the English language
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Smoking Abstinence | Assessed from week 3-29, week 29 reported | Smoking status will be assessed at baseline and each of the follow-up assessments using point prevalence abstinence (PPA) measures verified with carbon monoxide and saliva cotinine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anxiety Sensitivity Mechanistic Target | Assessed from week 3-29, week 7 reported (end of treatment) | Anxiety sensitivity was assessed using the Anxiety Sensitivity Index-3, which is an 18 item measure of fear of bodily sensations. Participants rated their concern regarding the possible negative consequences of internal anxiety-related sensations. Scores range from 0-72, with higher scores indicated greater sensitivity to bodily sensations (worse outcome). |
| Panic Symptoms Mechanistic Target | Assessed from week 3-29, week 29 reported (6-month follow-up) | Panic disorder severity scale is a 7-item measure assessing the severity of seven features of panic: frequency of panic attacks, distress during panic attacks, anticipatory anxiety, agoraphobic fear and avoidance, interoceptive fear and avoidance, impairment of work functioning, and impairment of social functioning. Items are rated on a five-point Likert scale ranging from 0 (none) to 4 (extreme), with a total possible score of 28. Higher scores indicate greater severity and impairment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PSRT_DCS Individuals in this condition will receive 7 weeks of panic and smoking reduction treatment (PSRT) and one pill of d-cycloserine (DCS) one hour prior to sessions 3, 4, and 5 (i.e., 3 single doses). Participants will also be given nicotine replacement therapy as part of PSRT (i.e., the patch).
d-cycloserine: d-cycloserine is a medication thought to be associated with fear extinction. | 27 |
| PSRT_PBO Individuals in this condition will receive 7 weeks of panic and smoking reduction treatment (PSRT) and one pill placebo dose one hour prior to sessions 3, 4, and 5 (i.e., 3 single doses). Participants will also be given nicotine replacement therapy as part of PSRT (i.e., the patch).
Pill Placebo | 26 |
| Total | 53 |
Baseline characteristics
| Characteristic | Total | PSRT_DCS | PSRT_PBO |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants | 27 Participants | 26 Participants |
| Age, Continuous | 35.91 years STANDARD_DEVIATION 12.61 | 35.19 years STANDARD_DEVIATION 12.37 | 36.64 years STANDARD_DEVIATION 12.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 27 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 49 Participants | 26 Participants | 23 Participants |
| Region of Enrollment United States | 53 participants | 27 participants | 26 participants |
| Sex: Female, Male Female | 37 Participants | 19 Participants | 18 Participants |
| Sex: Female, Male Male | 16 Participants | 8 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 26 |
| other Total, other adverse events | 2 / 27 | 3 / 26 |
| serious Total, serious adverse events | 0 / 27 | 0 / 26 |
Outcome results
Primary
Smoking Abstinence
Smoking status will be assessed at baseline and each of the follow-up assessments using point prevalence abstinence (PPA) measures verified with carbon monoxide and saliva cotinine.
Time frame: Assessed from week 3-29, week 29 reported
Population: Intent to treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PSRT_DCS | Smoking Abstinence | 8.25 percentage of participants |
| PSRT_PBO | Smoking Abstinence | 12.35 percentage of participants |
95% CI: [-2.25, 0.97]two-phase growth curve model
Secondary
Anxiety Sensitivity Mechanistic Target
Anxiety sensitivity was assessed using the Anxiety Sensitivity Index-3, which is an 18 item measure of fear of bodily sensations. Participants rated their concern regarding the possible negative consequences of internal anxiety-related sensations. Scores range from 0-72, with higher scores indicated greater sensitivity to bodily sensations (worse outcome).
Time frame: Assessed from week 3-29, week 7 reported (end of treatment)
Population: Intent to treat analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PSRT_DCS | Anxiety Sensitivity Mechanistic Target | 15.37 unstandardized units | Standard Deviation 10.38 |
| PSRT_PBO | Anxiety Sensitivity Mechanistic Target | 17.80 unstandardized units | Standard Deviation 13.77 |
Comparison: At end-of-treatmentp-value: 0.03895% CI: [0.25, 7.94]two-phase growth curve model
Secondary
Panic Symptoms Mechanistic Target
Panic disorder severity scale is a 7-item measure assessing the severity of seven features of panic: frequency of panic attacks, distress during panic attacks, anticipatory anxiety, agoraphobic fear and avoidance, interoceptive fear and avoidance, impairment of work functioning, and impairment of social functioning. Items are rated on a five-point Likert scale ranging from 0 (none) to 4 (extreme), with a total possible score of 28. Higher scores indicate greater severity and impairment.
Time frame: Assessed from week 3-29, week 29 reported (6-month follow-up)
Population: Intent to treat analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PSRT_DCS | Panic Symptoms Mechanistic Target | 5.36 unstandardized units | Standard Deviation 6.96 |
| PSRT_PBO | Panic Symptoms Mechanistic Target | 5.40 unstandardized units | Standard Deviation 5.93 |
Comparison: At 6 month follow-upp-value: 0.00395% CI: [1.15, 5.26]two-phase growth curve model