The Effect of Cycloserine on Smoking Behavior in Nicotine Dependent Smokers

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00633256
• Collaborator: VA Connecticut Healthcare System (U.S. Fed)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 14
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

A total of 20 subjects will participate in this four week, between groups, double-blind, placebo controlled study. Subjects will participate in two experimental sessions separated by approximately one week. Subjects will be randomized to receive either 50 mg cycloserine or placebo combined with cue exposure. Several physiological and subjective outcome measures (e.g., heart rate, blood pressure, galvanic skin response) will be obtained during the sessions. Experimental sessions will last approximately 4.5 hours with follow-up sessions lasting approximately thirty minutes. Our aims are:

1. To examine the effect of cycloserine vs. placebo on extinction of smoking cue reactivity in overnight abstinent smokers. Reactivity to smoking cues will be captured with self-report smoking urges and physiological measures (heart rate, blood pressure, and skin conductance).

We hypothesize that cycloserine, relative to placebo, will facilitate extinction of smoking cue reactivity.

1. To examine the effect of cycloserine vs. placebo when combined with two 4.5 hour laboratory cue exposure training sessions, on smoking behavior in smokers. Smoking behavior will be measured with self-report smoking and saliva cotinine levels.

2. To examine the effect of cycloserine vs. placebo on memory performance in nicotine dependent smokers. Memory performance will be measured with verbal learning, recognition and recall tasks.

1. To examine the safety and tolerability of cycloserine treatment in smokers. We hypothesize that cycloserine will be well tolerated by smokers.

Condition or Disease	Intervention/Treatment	Phase
Smoking	Drug: Cycloserine; Drug: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of Cycloserine on Smoking Behavior in Nicotine Dependent Smokers.
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cycloserine 50 mg cycloserine	Drug: Cycloserine; 50 mg Cycloserine given in two separate experimental sessions separated by approximately one week.; Other Names: Closina Aspen, Austral. Cycloserine Capsules USP 29 Cycloserine (TM)King, UK D-cycloserin IFET (IFET), Gr. Proserine Hawon, Thai. Seromycin - 250 MG - Capsule Dura Pharmaceuticals Seromycin - 250 MG - Oral Capsule Eli Lilly Seromycin (FM) Lilly, Canad. Seromycin Dura, USA Seromycin Lilly, Hong Kong Seromycin With Isoniazid - 250 MG - Capsule Eli Lilly Siklocap
Sham Comparator: Placebo Matched placebo	Drug: Placebo; Matched placebo for subjects randomized to placebo arm. Given in two experimental sessions separated by approximately one week.

Outcome Measures

Primary Outcome Measures

1. Cigarettes Smoked Per Day [1 week follow-up]

   The number of cigarettes smoked per day at the 1 week follow up time point.

Secondary Outcome Measures

1. Cigarettes Smoked Per Day [4 Week Followup]

   The number of cigarettes smoked per day at the 4-week follow up timepoint.

2. Urinary Cotinine Level [4 Week Follow-up Timepoint]

   Urinary Cotinine level at the 4-week follow up timepoint

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• female and male smokers, aged 18 to 55 years;

• history of smoking daily for the past 12 months, at least 10 cigarettes daily;

• CO level > 10ppm;

• for women: not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods other than OCP;

• Non-treatment seeking nicotine dependent smokers.

Exclusion Criteria:

• history of heart disease, renal or hepatic diseases or other medical conditions that the physician investigator deems as contraindicated for the patient to be in the study;

• regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics) and/or recent psychiatric diagnosis and treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia and panic disorder within the past year;

• current dependence on alcohol or on drugs other than nicotine;

• regular use of any other tobacco products than cigarettes, including smokeless tobacco and nicotine products;

• allergy to cycloserine;

• subjects with epilepsy or a history of seizures;

• Treatment seeking nicotine dependent smokers.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	West Haven VA	West Haven	Connecticut	United States	06516

Sponsors and Collaborators

• Yale University
• VA Connecticut Healthcare System

Investigators

• Principal Investigator: James Poling, Ph.D., Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Santa Ana EJ, Rounsaville BJ, Frankforter TL, Nich C, Babuscio T, Poling J, Gonsai K, Hill KP, Carroll KM. D-Cycloserine attenuates reactivity to smoking cues in nicotine dependent smokers: a pilot investigation. Drug Alcohol Depend. 2009 Oct 1;104(3):220-7. doi: 10.1016/j.drugalcdep.2009.04.023. Epub 2009 Jul 9.

• Responsible Party: James Poling, Research Scientist, Yale University
• ClinicalTrials.gov Identifier: NCT00633256
• Other Study ID Numbers: 0601001031
• First Posted: Mar 11, 2008
• Last Update Posted: Apr 11, 2012
• Last Verified: Mar 1, 2012

• Additional relevant MeSH terms: Isoniazid; Cycloserine

Study Results

Participant Flow

Arm/Group Title	Cycloserine	Placebo
Arm/Group Description	50 mg cycloserine	Matched placebo
Period Title: Overall Study
STARTED	12	13
COMPLETED	8	10
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Cycloserine	Placebo	Total
Arm/Group Description	50 mg cycloserine	Matched placebo	Total of all reporting groups
Overall Participants	12	13	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	13 100%	25 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.1 (6.2)	41.5 (11.5)	41.3 (9.1)
Sex: Female, Male (Count of Participants)
Female	6 50%	7 53.8%	13 52%
Male	6 50%	6 46.2%	12 48%
Region of Enrollment (participants) [Number]
United States	12 100%	13 100%	25 100%

Outcome Measures

1. Primary Outcome

Title	Cigarettes Smoked Per Day
Description	The number of cigarettes smoked per day at the 1 week follow up time point.
Time Frame	1 week follow-up

Outcome Measure Data

Analysis Population Description

The number of participants used for analysis were those who completed the 4-week follow-up timepoint.

Arm/Group Title	Cycloserine	Placebo
Arm/Group Description	50 mg cycloserine	Matched placebo
Measure Participants	8	8
Mean (Standard Deviation) [Cigarettes per day]	10.3 (6.3)	13.9 (12.7)

2. Secondary Outcome

Title	Cigarettes Smoked Per Day
Description	The number of cigarettes smoked per day at the 4-week follow up timepoint.
Time Frame	4 Week Followup

Outcome Measure Data

Analysis Population Description

The number of subjects in the study at the 4-week timepoint.

Arm/Group Title	Cycloserine	Placebo
Arm/Group Description	50 mg cycloserine	Matched placebo
Measure Participants	8	8
Mean (Standard Deviation) [Cigarettes per day]	9.9 (7.7)	11.0 (9.2)

3. Secondary Outcome

Title	Urinary Cotinine Level
Description	Urinary Cotinine level at the 4-week follow up timepoint
Time Frame	4 Week Follow-up Timepoint

Outcome Measure Data

Analysis Population Description

Subjects used for analysis are those who reached the 4 week followup timepoint.

Arm/Group Title	Cycloserine	Placebo
Arm/Group Description	50 mg cycloserine	Matched placebo
Measure Participants	8	8
Mean (Standard Deviation) [Mean ng/ml]	1645.5 (1180.8)	2062.6 (1091.1)

Adverse Events

Arm/Group Title	Cycloserine		Placebo
Arm/Group Description	50 mg cycloserine		Matched placebo
All Cause Mortality
	Cycloserine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cycloserine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Cycloserine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/13 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.