Effects of Nicotine Replacement Therapy and D-cycloserine on Nicotine Treatment Seekers

The investigators previously developed a cigarette cue extinction treatment (CET) procedure in non-treatment seeking volunteer smokers in our nicotine laboratory. The goal of Cue Extinction Treatment is to un-pair a behavioral or autonomic response from the stimulus that triggers it. This is accomplished through repeated exposure to that trigger, while removing the patient's ability to act out the conditioned response. In the present study, the trigger is a lit cigarette, and the response the investigators seek to un-pair is cigarette craving. In the procedure the investigators have previously developed and intend to use again, the participant is shown a pack of his brand of choice cigarettes. The researcher removes a cigarette from the pack, lights it, and asks the participant to hold the cigarette without smoking it for 90 seconds. This procedure is repeated seven times over the course of a six-hour lab session. The investigators hope to boost the clinical response to smoking cue exposure therapy in quitters on NRT (nicotine replacement therapy) pretreatment by pharmacological augmentation with the partial NMDA receptor agonist D-cycloserine (DCS). Behavioral extinction training is a form of learning that may be modulated by NMDA receptor mediated glutamate transmission. The study's main hypothesis is that the partial NMDA receptor agonist D-cycloserine (DCS) facilitates cue exposure training and may prevent relapse to smoking. The aim of the proposed study is to assess whether DCS-facilitation of cue-exposure therapy improves abstinence among smokers on the nicotine patch seeking treatment. Development of an effective treatment strategy to enhance the effectiveness of NRTs would have a direct and significant positive impact on public health.

Study Overview

• Status: Withdrawn
• Conditions: Cigarette Smoking
• Intervention / Treatment: Drug: D-cycloserine; Drug: Nicotine Replacement Therapy (patch); Behavioral: Smoking Cue Exposure; Behavioral: Progressive Muscle Relaxation; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Seeking treatment for nicotine dependence
2. Medically healthy on the basis of physical examination and medical history, vital signs, EKG, and laboratory tests, with a negative pregnancy test for females.
3. A DSM-IV diagnosis of nicotine dependence with physiological dependence. Has smoked at least 15 cigarettes daily for at least two years.
4. Able to perform study procedures.
5. Males or females between the ages of 21-55 yrs.
6. Female Participants agree to use an effective method of birth control

Exclusion Criteria:

1. A DSM-IV diagnosis of lifetime history of abuse or dependence on alcohol or drugs other than nicotine
2. Current Axis I diagnosis or current treatment with psychotropic medications (within last three months).
3. Lifetime history of schizophrenia or other psychotic disorders, bipolar disorder, or anxiety disorders.
4. Participants on parole or probation
5. History of significant recent violent behavior, e.g., one or more incidents of violent behavior in the past year resulting in physical damage.
6. Unstable medical condition, Blood pressure > 140/90, Pregnancy.
7. History of allergic reaction to nicotine patch.
8. History of hypersensitivity to cycloserine.
9. Any history of seizures
10. History of renal disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: D-cycloserine; The investigators will randomize participants to either DCS 250 mg or placebo, administered daily for four days.	Drug: D-cycloserine; Drug: Nicotine Replacement Therapy (patch); Behavioral: Smoking Cue Exposure; Behavioral: Progressive Muscle Relaxation
PLACEBO_COMPARATOR: Gelatin Capsule; The investigators will randomize participants to either DCS 250 mg or placebo, administered daily for four days.	Drug: Nicotine Replacement Therapy (patch); Behavioral: Smoking Cue Exposure; Behavioral: Progressive Muscle Relaxation; Drug: Placebo; The investigators will administer Gelatin Capsule instead of D-Cycloserine in a double blind fashion to some of study subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Cigarettes Smoked	Smoking Diary kept of daily cigarette smoking.	3 months

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Investigators: Principal Investigator: S. Rob Vorel, MD, PhD, New York State Psychiatric Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2013
• Primary Completion (ACTUAL): May 1, 2015
• Study Completion (ACTUAL): September 1, 2016

Study Registration Dates

• First Submitted: July 10, 2013
• First Submitted That Met QC Criteria: July 22, 2013
• First Posted (ESTIMATE): July 25, 2013

Study Record Updates

• Last Update Posted (ACTUAL): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 5, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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: 6769