SchizophreniaPhase 4NCT00373126
The Effects of Nicotine Withdrawal on Reward Responsivity in Schizophrenia
A Phase 4 study testing transdermal nicotine patch in people with Schizophrenia and Schizoaffective Disorder, run by North Suffolk Mental Health Association at 1 site in United States.
Trial summary
It has been suggested that patients with schizophrenia smoke in order to produce amelioration of dysfunctional dopaminergic pathways allowing them to experience pleasure and satisfaction and overcome anhedonia. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- transdermal nicotine patch
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2005to not given
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Schizophrenia group inclusion criteria:
- DSM IV diagnosis of schizophrenia with stable symptoms and a stable dose of antipsychotic medications for at least 4 weeks
- Age 18-55 inclusive
- Able to provide informed consent
- Self reported smoking of 20 or more cigarettes per day for at least 12 months
- FTND score of >/= 5
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- Expired air CO of >/= 10 ppm
- WRAT-3 IQ score greater than or equal to 35
- Normal or corrected to normal vision
- Control group inclusion criteria: Same as above except for diagnosis of schizophrenia
Who cannot join
- Schizophrenia Group exclusion criteria:
- Current unstable serious medical illness such as uncontrolled high blood pressure, untreated ischemic heart disease
- Use of any cholinesterase inhibitor such as galantamine in the past 3 months
- History of skin diseases (e.g., psoriasis), skin allergies, or strong reactions to topical preparations, medical dressings, tapes or nicotine patches
- Treated with an investigational medication in the last 30 days
- Currently or planning to become pregnant in the next 8 weeks as verified by positive pregnancy test or childbearing potential and not using adequate contraception
Show all 11Show fewer
- Substance abuse in the past month: Self reported or diagnosed during chart review and verified by positive salivary test for cocaine, methamphetamine, amphetamine, ethanol, THC, opiates or PCP at screen
- Current major depressive disorder
- History of cognitive impairment due to other disorders such as head injury, dementia, general medical condition
- Diagnosis of mental retardation
- Control group exclusion criteria: Same as above except for diagnosis of schizophrenia or family history of psychiatric illness
Trial locations and contacts
1 site in 1 country.
United States1 site
Freedom Trail Clinic, 25 Staniford Street
Boston, Massachusetts, 02114
About this study
Official title: A Double-Blind, Placebo-Controlled Trial of Reward Responsivity During Nicotine Withdrawal in Smokers With Schizophrenia and Normal Controls
It has been suggested that patients with schizophrenia smoke in order to produce amelioration of dysfunctional dopaminergic pathways allowing them to experience pleasure and satisfaction and overcome anhedonia. No studies have assessed the effects of nicotine withdrawal on reward responsivity in patients with schizophrenia. The investigators believe that an understanding of this is crucial if improved treatments for nicotine dependence are to be developed for this patient population. If this group already has deficits in reward responsivity as a symptom of the disease then they may be particularly prone to the effects of nicotine withdrawal on reward systems. Smoking cessation may lead to a further decrease in their responsivity to pleasurable stimuli and worsening anhedonia. Treatments for smoking cessation may need to ameliorate any increased deficits if they are likely to be effective in patients with schizophrenia.
Read the detailed description
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.
Principal Aims:
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.
Secondary aims:
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
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- transdermal nicotine patch
- Keywords
- nicotine, schizophrenia, reward, withdrawal
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transdermal nicotine patchDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Reward Responsivity using a signal detection task
Secondary outcomes (2)
Cognitive drug research cognitive battery
Source monitoring task to assess verbal memory
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2006 (estimated)
- Study startApr 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- North Suffolk Mental Health Association
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital
- Investigators
- A E Evins, MD MPH, Principal investigator, North Suffolk Mental Health Association
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00373126
- Sponsor's protocol ID
- CORRC 06-05
- Other IDs
- 2005P-001753
- Status last verified
- May 2009
- First submitted
- 5 Sep 2006
- Last updated
- 15 May 2009
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled Trial of Reward Responsivity During Nicotine Withdrawal in Smokers With Schizophrenia and Normal Controls
- ClinicalTrials.gov ID
- NCT00373126
- Acronym / sponsor ID
- CORRC 06-05
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Keywords
- nicotine, schizophrenia, reward, withdrawal
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- North Suffolk Mental Health AssociationUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital
- Study start
- Apr 2005
- First posted
- 7 Sep 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
It has been suggested that patients with schizophrenia smoke in order to produce amelioration of dysfunctional dopaminergic pathways allowing them to experience pleasure and satisfaction and overcome anhedonia. No studies have assessed the effects of nicotine withdrawal on reward responsivity in patients with schizophrenia. The investigators believe that an understanding of this is crucial if improved treatments for nicotine dependence are to be developed for this patient population. If this group already has deficits in reward responsivity as a symptom of the disease then they may be particularly prone to the effects of nicotine withdrawal on reward systems. Smoking cessation may lead to a further decrease in their responsivity to pleasurable stimuli and worsening anhedonia. Treatments for smoking cessation may need to ameliorate any increased deficits if they are likely to be effective in patients with schizophrenia.
Detailed description
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.
Principal Aims:
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.
Secondary aims:
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- DSM IV diagnosis of schizophrenia with stable symptoms and a stable dose of antipsychotic medications for at least 4 weeks
- Age 18-55 inclusive
- Able to provide informed consent
- Self reported smoking of 20 or more cigarettes per day for at least 12 months
- FTND score of >/= 5
Key exclusion criteria (11 listed)
- Current unstable serious medical illness such as uncontrolled high blood pressure, untreated ischemic heart disease
- Use of any cholinesterase inhibitor such as galantamine in the past 3 months
- History of skin diseases (e.g., psoriasis), skin allergies, or strong reactions to topical preparations, medical dressings, tapes or nicotine patches
- Treated with an investigational medication in the last 30 days
- Currently or planning to become pregnant in the next 8 weeks as verified by positive pregnancy test or childbearing potential and not using adequate contraception
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| transdermal nicotine patch | Drug | – |
Primary outcome
Reward Responsivity using a signal detection task
2 secondary outcomes
Cognitive drug research cognitive battery
Source monitoring task to assess verbal memory
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
A E Evins, MD MPH principal investigator
North Suffolk Mental Health Association
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing transdermal nicotine patch in people with Schizophrenia and Schizoaffective Disorder, run by North Suffolk Mental Health Association at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reward Responsivity using a signal detection task. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2009.