Cognitive Remediation With D-Cycloserine

Cognitive Remediation With D-cycloserine to Improve Smoking Cessation Outcomes

One hundred seventy-five eligible participants will be enrolled with aim of randomizing 60 to a double-blind, placebo-controlled trial of D-cycloserine added to cue-exposure treatment to prevent relapse to smoking. Subjects who sign an informed consent, meet inclusion criteria, and demonstrate response to cue reactivity at the screening visit, will either be:

• started on approximately 3 weeks of either nicotine replacement therapy (NRT) at a dose of either 14 or 21 mg/day or varenicline titrated to 1.0 mg bid; decision of which method to use to quit smoking will be based on participant choice as well as taking into account any medical contraindications to either therapy.
• evaluated to confirm abstinence from smoking. Recently abstinent participants referred by a smoking cessation clinic, PCP or self referred must have an expired air CO < 10 ppm to confirm abstinence.

Subjects who are able to demonstrate 18-24 hours of abstinence prior to the first Cue Exposure Therapy Visit (CET I) will be eligible to be randomized to two visits of study medication and cue exposure treatment, spaced five to nine days apart. Subjects will complete 2 follow-up visits at 2-4 days and four weeks after the last CET visit. The entire study involves twelve visits and will last approximately ten weeks. For recently abstinent participants referred by a smoking cessation clinic, PCP or self referred, the study involves 7 visits (screening and baseline visit will be merged into one and there is no CBT component) and will last approximately 7 weeks.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Placebo; Drug: D-cycloserine

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital - Center For Addiction Medicine

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:

• Participants must have smoked an average of ≥ 10 cigarettes/day during the past 6 months
• have expired air CO ≥ 10 ppm or urine cotinine ≥ 100 ng/mL
• meet DSM-IV criteria for nicotine dependence
• aged 18 - 65
• Recently abstinent participants referred by a PCP, smoking cessation clinic or self referred must have an expired air CO < 10 ppm to confirm abstinence

Exclusion Criteria:

• Severe or uncontrolled medical or psychiatric illness
• History of multiple hospitalizations within the last six months for an ongoing medical condition
• Any significant, current and unstable cardiovascular disease, end stage renal failure, severe COPD requiring oxygen, any current unstable neurological disease, a history of seizures or epilepsy, or a history of head trauma with lasting neurological sequelae, will be excluded for their safety.
• Major depressive episode, mania or mixed episode in the prior 6 months
• Lifetime history of psychosis, delusional disorder, organic mental disorder by DSM-IV criteria, or ongoing cognitive impairment will also be excluded for their safety,
• Current excessive use of alcohol (>21 drinks/week in female subjects; >28 drinks/week in male subjects)
• Current use of illicit drugs.
• Current steroid use, current, daily use of benzodiazepines, or participants who are unwilling to modify their benzodiazepine use will.
• Pregnant or breastfeeding women will be excluded, as well as women of childbearing potential who will not use a medically acceptable method of contraception (i.e. IUD, oral contraceptives).
• Participants who are deaf, blind, or experience any other significant sensory impairment that would preclude them from completing study procedures will also be excluded, as well as participants who are unable to understand study procedures or provide informed consent.
• Participants receiving isoniazid or ethionamide, or who have a known sensitivity to D-cycloserine.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 50 mg capsule,single dose, twice, one week apart, by mouth	Drug: Placebo
Active Comparator: D-cycloserine; 50 mg capsule,single dose, twice, one week apart, by mouth	Drug: D-cycloserine; 2 single weekly doses, 50 mg capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of D-cycloserine + Cue-exposure Treatment on Continuous Abstinence From Tobacco Smoking.	Participants assigned to receive D-cycloserine + CET will achieve better maintenance of tobacco abstinence, as assessed with self-report and saliva cotinine measurements, than those who receive placebo + CET at week 6 follow up visits	Up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of D-cycloserine + Cue-exposure Treatment on Skin Conductance	Recently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (skin conductance) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Assessment of skin conductance was made after each audio recording was presented. The skin conductance mean was obtained for each script (smoking vs neutral). Differences in responsivity (skin conductance) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.	6 weeks
Effect of D-cycloserine + Cue-exposure Treatment on Heart Rate	Recently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (heart rate) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Heart rate measurement was obtained after each audio recording was presented. The heart rate mean was obtained for each script (smoking vs neutral). Differences in responsivity (heart rate) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.	6 weeks
Effect of D-cycloserine + Cue-exposure Treatment on Electromyogram	Recently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (electromyogram) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Electromyogram of the corrugator (EMGc)measurement was obtained after each audio recording was presented. The EMGc mean was obtained for each script (smoking vs neutral). Differences in responsivity (EMGc) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.	6 weeks
Effect of D-cycloserine + Cue-exposure Treatment on Craving	Recently abstinent smokers assigned to receive D-cycloserine + CET will have less craving at the Post-Extinction Assessment than those who receive placebo + CET The scale used to measure craving was a Visual Analogue Scale 0 (no desire at all) - 7 (unable to resist) Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Craving level was obtained after each audio recording was presented. The craving mean was obtained for each script (smoking vs neutral). Differences in craving level response to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.	6 weeks
Effect of D-cycloserine + Cue-exposure Treatment on Attentional Bias Toward Smoking Cuesmeasured With the Emotional Stroop Task	Recently abstinent smokers assigned to receive D-cycloserine + CET will have less attentional bias (Smoking Stroop task) toward smoking cues at the Post-Extinction Assessment than those who receive placebo + CET The Emotional Stroop uses smoking-related words and neutral words to measure attentional bias toward smoking related cues. Attentional bias is a central feature of many cognitive theories of addiction and can be measured with an emotional analog of the Stroop task. In this task, participants name the colors in which words are printed, and the words vary in their relevance to smoking. Extensive research has shown that patients are often slower to name the color of a word associated with concerns relevant to their clinical condition due to distraction by the meaning of the word(Williams, Mathews et al. 1996). The Stroop interference Score is obtained by subtracting Reaction Time (RT) to smoking minus the Reaction Time to neutral	Baseline and week 6

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: July 19, 2011
• First Submitted That Met QC Criteria: July 21, 2011
• First Posted (Estimate): July 22, 2011

Study Record Updates

• Last Update Posted (Actual): September 26, 2018
• Last Update Submitted That Met QC Criteria: August 29, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: craving; D-cycloserine; Cognitive remediation; Smoking cues; physiologic reactivity
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Anti-Bacterial Agents; Antitubercular Agents; Antibiotics, Antitubercular; Anti-Infective Agents, Urinary; Renal Agents; Cycloserine
• Other Study ID Numbers: 2011P000411