Enhancing Panic and Smoking Reduction Treatment With D-Cycloserine (DCS/PSRT)

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.

Study Overview

• Status: Completed
• Conditions: Panic Attack; Nicotine Addiction
• Intervention / Treatment: Drug: Pill Placebo; Drug: d-cycloserine; Drug: Nicotine replacement therapy; Behavioral: Panic and Smoking Reduction Treatment

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78712
      • University of Texas at Austin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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: d-cycloserine; DCS; 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: patch, NRT, nicoderm,; 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: PSRT, CBT, cognitive behavioral therapy, panic reduction, smoking cessation
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: sugar pill; 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: patch, NRT, nicoderm,; 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: PSRT, CBT, cognitive behavioral therapy, panic reduction, smoking cessation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Assessed from week 3-29, week 29 reported

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Assessed from week 3-29, week 7 reported (end of treatment)
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.	Assessed from week 3-29, week 29 reported (6-month follow-up)

Collaborators and Investigators

• Sponsor: University of Texas at Austin

Publications and helpful links

General Publications

• Smits JAJ, Zvolensky MJ, Otto MW, Piper ME, Baird SO, Kauffman BY, Lee-Furman E, Alavi N, Dutcher CD, Papini S, Rosenfield B, Rosenfield D. Enhancing panic and smoking reduction treatment with D-Cycloserine: A pilot randomized clinical trial. Drug Alcohol Depend. 2020 Mar 1;208:107877. doi: 10.1016/j.drugalcdep.2020.107877. Epub 2020 Jan 22.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2013
• Primary Completion (ACTUAL): October 1, 2018
• Study Completion (ACTUAL): October 1, 2018

Study Registration Dates

• First Submitted: September 10, 2013
• First Submitted That Met QC Criteria: September 12, 2013
• First Posted (ESTIMATE): September 17, 2013

Study Record Updates

• Last Update Posted (ACTUAL): May 19, 2021
• Last Update Submitted That Met QC Criteria: May 17, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Anxiety Disorders; Tobacco Use Disorder; Panic Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Antimetabolites; Anti-Bacterial Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Antitubercular Agents; Antibiotics, Antitubercular; Anti-Infective Agents, Urinary; Renal Agents; Nicotine; Cycloserine
• Other Study ID Numbers: R34DA034658 (NIH)