The Effects of Nicotine Withdrawal on Reward Responsivity in Schizophrenia
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|ClinicalTrials.gov Identifier: NCT00373126|
Recruitment Status : Completed
First Posted : September 7, 2006
Last Update Posted : May 15, 2009
|Condition or disease||Intervention/treatment||Phase|
|Schizophrenia Schizoaffective Disorder||Drug: transdermal nicotine patch||Phase 4|
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Heavy smoking continues to represent a significant public health problem for people in the general population and for people with major mental illness. Twenty-four percent of adults in the general population smoke and it has been estimated that 74-92% of people with schizophrenia smoke. While effective treatments for smoking cessation have been developed, response rates are modest and relapse rates are high. Approximately 70% of people who quit smoking with effective treatments relapse to smoking within one year. A syndrome of negative affect and anhedonia has been described as an important component in maintenance of dependence on nicotine. It has also been suggested that preventing the syndrome of anhedonia and negative affect during early abstinence may reduce relapse rates. If the syndrome of anhedonia can be measured objectively and quantitatively, we will be better able to test treatments for this withdrawal syndrome. It is our hypothesis that the syndrome of anhedonia during early abstinence from nicotine is quantifiable as a deficit in reward responsivity.
Animal studies suggest that nicotine withdrawal is associated with an alteration in reward responsivity. Brain stimulation reward thresholds have been used to measure anhedonia and responsivity to reward in animal models. Nicotine withdrawal has been associated with a significant decrease in brain reward function as measured by elevations in brain reward thresholds that persist for 4 days. Nicotine withdrawal has also been associated with failure of conditioning to an environment paired with novel stimuli, possibly due to a decrease in reward associated with novel stimuli. Drug withdrawal states have also been associated with inhibition of mesolimbic release in murine models.
We propose a randomized placebo controlled trial to investigate the effects of nicotine abstinence on reward responsivity in patients with no major mental illness and in patients with schizophrenia.
Aim 1: To evaluate the effects of nicotine withdrawal on a measure of reward responsivity Hypothesis 1a: Normal controls and subjects with schizophrenia will demonstrate deterioration on a measure of reward responsivity during abstinence (placebo condition) compared to baseline. (Primary Outcome Measure)
Aim 2: To evaluate the effects of transdermal nicotine on reward responsivity during abstinence.
Hypothesis 2a: Normal controls and subjects with schizophrenia will demonstrate greater response bias toward a rewarded condition following transdermal nicotine administration relative to placebo patch during a 3 day period of abstinence.
Aim 3: To evaluate the effects of smoking abstinence and transdermal nicotine on a measure of reward responsivity in patients with schizophrenia who smoke relative to normal control smokers.
Hypothesis 3a: Subjects with schizophrenia will demonstrate decreased reward responsivity during all conditions (baseline, nicotine replacement therapy condition and placebo condition) relative to normal controls.
Aim 4: To evaluate the effects of nicotine withdrawal on cognitive function in smokers Hypothesis 4a: Normal controls and subjects with schizophrenia will demonstrate poorer performance on tests of cognition following placebo administration compared with baseline and nicotine conditions.
We propose to test the effects of smoking abstinence and nicotine replacement therapy, using nicotine transdermal patch on a measure of reward responsivity in patients who smoke. We propose a randomized placebo controlled crossover trial with the primary outcome measure being Response bias using a signal detection task.
Subjects are 70 patients with schizophrenia who smoke and 70 normal control smokers who do not have a major mental illness and who are matched for age, sex and nicotine dependence. Though we expect to consent 70 subjects in each group, we expect only 20 subjects in each group to complete the study
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Crossover Assignment|
|Official Title:||A Double-Blind, Placebo-Controlled Trial of Reward Responsivity During Nicotine Withdrawal in Smokers With Schizophrenia and Normal Controls|
|Study Start Date :||April 2005|
- Reward Responsivity using a signal detection task
- Cognitive drug research cognitive battery
- Source monitoring task to assess verbal memory
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00373126
|United States, Massachusetts|
|Freedom Trail Clinic, 25 Staniford Street|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||A E Evins, MD MPH||North Suffolk Mental Health Association|