Neural Substrates in Nicotine Withdrawal

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01001520
First received: October 22, 2009
Last updated: May 29, 2014
Last verified: May 2014
Results First Received: January 7, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Tobacco Use Disorder
Interventions: Drug: Tolcapone
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment began in March 2010. Former study subjects with a known catechol-O-methyltransferase (COMT) genotype and who asked to be contacted for future studies were invited to participate, as well as potential subjects who called our center in response to advertising. All sessions were completed in our clinic at the University of Pennsylvania.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
2670 subjects completed initial screening over the phone; 669 (25%) were eligible. Of these, 418 (62%) scheduled an in-person screening visit; 218 (50%) attended this visit. 73 (17%) provided blood samples to determine final eligibility, based on genetic & liver function tests. 54 (74%) reached final eligibility; 46 (85%) started study medication.

Reporting Groups
  Description
Placebo First, Then Tolcapone

Subjects were asked to take study medication each day during two 11-day study medication periods. Between the two study medication periods was a washout period (no medication or visits) that lasted at least 10 days. During this washout period, subjects did not take any study medication and were asked to return to their normal smoking levels.

Study medication assignment for each subject was randomized and counterbalanced, meaning approximately 50% of subjects took placebo during the first medication period, followed by tolcapone during the second medication period.

During the placebo medication period, subjects followed a medication regimen and took capsules that were identical to those in the active tolcapone medication period (see protocol section for complete description).

Tolcapone First, Then Placebo

Subjects were asked to take study medication each day during two 11-day study medication periods. Between the two study medication periods was a washout period (no medication or visits) that lasted at least 10 days. During this washout period, subjects did not take any study medication and were asked to return to their normal smoking levels.

Study medication assignment for each subject was randomized and counterbalanced, meaning approximately 50% of subjects took tolcapone during the first medication period, followed by a placebo during the second medication period.

During the active tolcapone medication period, subjects followed a tapered dosing schedule (see protocol section for complete description).


Participant Flow for 3 periods

Period 1:   Medication Period 1
    Placebo First, Then Tolcapone     Tolcapone First, Then Placebo  
STARTED     22     24  
COMPLETED     18     17  
NOT COMPLETED     4     7  
Withdrawal by Subject                 2                 2  
Ineligible: Positive Urine Drug Screen                 0                 3  
Ineligible: fMRI contraindicated metal                 0                 2  
Ineligible: Claustrophobia in fMRI                 2                 0  

Period 2:   Washout Period
    Placebo First, Then Tolcapone     Tolcapone First, Then Placebo  
STARTED     18     17  
COMPLETED     16     16  
NOT COMPLETED     2     1  
Withdrawal by Subject                 2                 1  

Period 3:   Medication Period 2
    Placebo First, Then Tolcapone     Tolcapone First, Then Placebo  
STARTED     16     16  
COMPLETED     16     13  
NOT COMPLETED     0     3  
Withdrawal by Subject                 0                 3  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Measurements were taken during their first study visit, the medical screening visit.

Reporting Groups
  Description
Entire Study Population Includes all subjects who were randomized to both study treatment groups (i.e., receive both placebo first and tolcapone first) and initiated study medication.

Baseline Measures
    Entire Study Population  
Number of Participants  
[units: participants]
  46  
Age  
[units: Years]
Mean ± Standard Deviation
  38.3  ± 12.2  
Age  
[units: participants]
 
<=18 years     0  
Between 18 and 65 years     46  
>=65 years     0  
Gender  
[units: participants]
 
Female     17  
Male     29  
Race/Ethnicity, Customized  
[units: Participants]
 
African American     15  
Caucasian     29  
More than one race     2  
Region of Enrollment  
[units: participants]
 
United States     46  
Nicotine Dependence [1]
[units: Scores on a scale]
Mean ± Standard Deviation
  4.8  ± 1.5  
Cigarettes smoked per day [2]
[units: Cigarettes smoked per day]
Mean ± Standard Deviation
  17.1  ± 4.9  
Number of years smoked [3]
[units: years]
Mean ± Standard Deviation
  21.8  ± 13.7  
[1] Determined by the Fagerstrom Test for Nicotine Dependence (FTND). The FTND is a 6-item, self-report measure of nicotine dependence derived from the Fagerstrom Tolerance Questionnaire. Scores range from 0-10; higher FTND scores indicate greater difficulty in quitting smoking. All subjects completed the FTND during the medical screening visit.
[2] During the medical screening visit, subjects were asked to self-report the number of cigarettes they smoked on an average day.
[3] During the medical screening visit, subjects were asked to self-report the number of years they have been a regular smoker (defined as smoking at least one cigarette per day).



  Outcome Measures
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1.  Primary:   Measure of Brain Activity: Blood Oxygen Level Dependent (BOLD) fMRI Signal Change During the "N-back" Working Memory Task (Brain Region: Right Dorsolateral Prefrontal Cortex; Right DLPFC)   [ Time Frame: At fMRI scan sessions - Days 8 and 29 ]

2.  Primary:   Measure of Brain Activity: Blood Oxygen Level Dependent (BOLD) fMRI Signal Change During the "N-back" Working Memory Task (Brain Region: Left Dorsolateral Prefrontal Cortex; Left DLPFC)   [ Time Frame: At fMRI scan sessions - Days 8 and 29 ]

3.  Primary:   Measure of Brain Activity: Blood Oxygen Level Dependent (BOLD) fMRI Signal Change During the "N-back" Working Memory Task (Brain Region: Dorsal Cingulate/Medial Prefrontal Cortex; MF/CG)   [ Time Frame: At fMRI scan sessions - Days 8 and 29 ]

4.  Primary:   Measure of Brain Activity: Blood Oxygen Level Dependent (BOLD) fMRI Signal Change During the "N-back" Working Memory Task (Brain Region: Posterior Cingulate Cortex; PCC)   [ Time Frame: At fMRI scan sessions - Days 8 and 29 ]

5.  Primary:   Measure of Brain Activity: Blood Oxygen Level Dependent (BOLD) fMRI Signal Change During the "N-back" Working Memory Task (Brain Region: Ventromedial Prefrontal Cortex; vmPFC)   [ Time Frame: At fMRI scan sessions - Days 8 and 29 ]

6.  Secondary:   Cognitive Performance: Accuracy   [ Time Frame: At fMRI scan sessions - Days 8 and 29 ]

7.  Secondary:   Cognitive Performance: Reaction Time   [ Time Frame: At fMRI scan sessions - Days 8 and 29 ]

8.  Secondary:   Subjective Symptoms: Smoking Behavior   [ Time Frame: Days 1 through 7 of each study period ]

9.  Secondary:   Subjective Symptoms: Cigarette Craving   [ Time Frame: Day 8 (fMRI scanning session) of each study period ]

10.  Secondary:   Subjective Symptoms: Withdrawal Symptoms   [ Time Frame: Day 8 of each study period ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Genetic studies, particularly imaging studies, have drawbacks such as small sample size and focus on single candidate genes; both can be said of this study.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Caryn Lerman, PhD
Organization: University of Pennsylvania
phone: 215-746-7141
e-mail: clerman@mail.med.upenn.edu


No publications provided


Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01001520     History of Changes
Other Study ID Numbers: 809858, R01DA026849
Study First Received: October 22, 2009
Results First Received: January 7, 2014
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration