DCS/PSRT: Enhancing Panic and Smoking Reduction Treatment With D-Cycloserine
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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). |
Drug: d-cycloserine
d-cycloserine is a medication thought to be associated with fear extinction.
Other Names:
Drug: Nicotine 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.
Other Names:
Behavioral: Panic 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.
Other Names:
|
| Placebo Comparator: 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). |
Drug: Pill Placebo
Other Names:
Drug: Nicotine 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.
Other Names:
Behavioral: Panic 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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Texas at Austin | Austin | Texas | United States | 78712 |
Sponsors and Collaborators
- University of Texas at Austin
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- R34DA034658
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | PSRT_DCS | PSRT_PBO |
|---|---|---|
| Arm/Group Description | 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. | 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 |
| Period Title: Overall Study | ||
| STARTED | 27 | 26 |
| End of Treatment | 21 | 20 |
| 1-month Follow-up | 22 | 19 |
| 4-month Follow-up | 19 | 16 |
| COMPLETED | 19 | 17 |
| NOT COMPLETED | 8 | 9 |
Baseline Characteristics
| Arm/Group Title | PSRT_DCS | PSRT_PBO | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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 | Total of all reporting groups |
| Overall Participants | 27 | 26 | 53 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
27
100%
|
26
100%
|
53
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
35.19
(12.37)
|
36.64
(12.85)
|
35.91
(12.61)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
19
70.4%
|
18
69.2%
|
37
69.8%
|
| Male |
8
29.6%
|
8
30.8%
|
16
30.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
3
11.5%
|
3
5.7%
|
| Not Hispanic or Latino |
27
100%
|
23
88.5%
|
50
94.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
1
3.8%
|
1
1.9%
|
| Asian |
1
3.7%
|
1
3.8%
|
2
3.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
1
3.8%
|
1
1.9%
|
| White |
26
96.3%
|
23
88.5%
|
49
92.5%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
27
100%
|
26
100%
|
53
100%
|
Outcome Measures
| Title | Smoking Abstinence |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat analysis |
| Arm/Group Title | PSRT_DCS | PSRT_PBO |
|---|---|---|
| Arm/Group Description | 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. | 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 |
| Measure Participants | 27 | 26 |
| Number [percentage of participants] |
8.25
30.6%
|
12.35
47.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PSRT_DCS, PSRT_PBO |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Logit difference (final values) |
| Estimated Value | 0.64 | |
| Confidence Interval |
(2-Sided) 95% -2.25 to 0.97 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.82 |
|
| Estimation Comments | ||
| Title | Anxiety Sensitivity Mechanistic Target |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat analysis |
| Arm/Group Title | PSRT_DCS | PSRT_PBO |
|---|---|---|
| Arm/Group Description | 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. | 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 |
| Measure Participants | 27 | 26 |
| Mean (Standard Deviation) [unstandardized units] |
15.37
(10.38)
|
17.80
(13.77)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PSRT_DCS, PSRT_PBO |
|---|---|---|
| Comments | At end-of-treatment | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .038 |
| Comments | 2-sided | |
| Method | two-phase growth curve model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.43 | |
| Confidence Interval |
(2-Sided) 95% 0.25 to 7.94 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.87 |
|
| Estimation Comments | ||
| Title | Panic Symptoms Mechanistic Target |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat analysis |
| Arm/Group Title | PSRT_DCS | PSRT_PBO |
|---|---|---|
| Arm/Group Description | 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. | 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 |
| Measure Participants | 27 | 26 |
| Mean (Standard Deviation) [unstandardized units] |
5.36
(6.96)
|
5.40
(5.93)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PSRT_DCS, PSRT_PBO |
|---|---|---|
| Comments | At 6 month follow-up | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .003 |
| Comments | 2-sided | |
| Method | two-phase growth curve model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.21 | |
| Confidence Interval |
(2-Sided) 95% 1.15 to 5.26 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1 |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Adverse event data was collected at each in-person appointmnet during the course of the study (baseline appointment through the 6-month follow-up). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | PSRT_DCS | PSRT_PBO | ||
| Arm/Group Description | 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. | 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 | ||
All Cause Mortality |
||||
| PSRT_DCS | PSRT_PBO | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/27 (0%) | 0/26 (0%) | ||
Serious Adverse Events |
||||
| PSRT_DCS | PSRT_PBO | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/27 (0%) | 0/26 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| PSRT_DCS | PSRT_PBO | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/27 (7.4%) | 3/26 (11.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 1/27 (3.7%) | 1 | 0/26 (0%) | 0 |
| Cardiac disorders | ||||
| Pericarditis | 0/27 (0%) | 0 | 1/26 (3.8%) | 1 |
| General disorders | ||||
| Chipped back bone | 0/27 (0%) | 0 | 1/26 (3.8%) | 1 |
| Migraine | 1/27 (3.7%) | 1 | 0/26 (0%) | 0 |
| Psychiatric disorders | ||||
| Anxiety | 0/27 (0%) | 0 | 1/26 (3.8%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
| Name/Title | Dr. Jasper Smits |
|---|---|
| Organization | Univeristy of Texas at Austin |
| Phone | 512-475-8095 |
| smits@utexas.edu |
- R34DA034658