Nicotine DependencePhase 2NCT01202955
Pilot Study of Tolcapone in Smokers
A Phase 2 study testing Tolcapone in people with Nicotine Dependence, run by University of Pennsylvania at 1 site in United States.
Trial summary
The goals of this within-subject pilot study are: (1) assess the feasibility and safety of administering the Catechol-O-Methyl-Transferase (COMT) inhibitor, tolcapone, to smokers, and (2) explore whether tolcapone may reduce abstinence-induced cognitive and affective symptoms that promote relapse. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Tolcapone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to Jun 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Healthy as determined by a responsible physician, based on a medical evaluation including history, physical and psychiatric examination, laboratory tests, liver function monitoring.
- Smokers who are between 18 and 55 years of age and have an IQ greater than 90.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions, listed in the consent form.
- Based upon self-report, subjects must smoke >10 cigarettes/day and be interested in quitting smoking in the next 6 months (i.e., treatment-seekers).
- Women of childbearing potential must consent to using a medically accepted method of birth control (e.g., condoms and spermicide, oral contraceptive, Depo-provera injection, contraceptive patch, tubal ligation).
Who cannot join
- Smoking Behavior
- Use of chewing tobacco or snuff
- Current enrollment or plans to enroll in another smoking cessation program in the next month
- Plan to use other nicotine substitutes or smoking cessation treatments in the next month
- Provide a baseline carbon monoxide (CO) reading < 10ppm
- Alcohol/Drug Exclusion Criteria
Show all 45Show fewer
- History of substance abuse and/or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, MDMA/ecstasy, or stimulants)
- Current alcohol consumption that exceeds >14 standard drinks/week for men and >7 standard drinks/week for women over the last 6 months
- Medication Exclusion Criteria
- Current use or recent discontinuation (within last 4-weeks) of any medication including the following:
- Any form of psychotropic medications including:
- antipsychotics,
- atypical antipsychotics,
- mood-stabilizers,
- anti-depressants (tricyclics, SSRI's, MAOI's, nonselective MAOIs, Wellbutrin/Zyban),
- anti-panic agents,
- anti-obsessive agents,
- anti-anxiety agents, and
- stimulants (e.g., Provigil, Ritalin)
- Varenicline
- Medication for chronic pain
- Anti-coagulants (e.g., Warfarin)
- Any heart medications
- Daily medication for asthma
- Apomorphine, dobutamine, isoproterenol, levodopa, methyldopa, or sympathomimetic (e.g., albuterol, pseudoephedrine)
- Current use of any smoking cessation medication.
- Medical Exclusion Criteria
- Women who are pregnant, planning a pregnancy, or lactating.
- History or current diagnosis of psychosis, major depression or bipolar disorder, schizophrenia, or any Axis 1 disorder as identified by the MINI.
- Serious or unstable disease within the past 6 months (e.g., cancer [except squamous cell carcinoma], heart disease, HIV, liver disease, Parkinson's disease).
- History of epilepsy or a seizure disorder.
- History or current diagnosis (last 6-months) of abnormal rhythms and/or tachycardia (>100 beats/minute); history or current diagnosis of chronic obstructive pulmonary disease (COPD), cardiovascular disease (stroke, angina, coronary heart disease), heart attack in the last 6 months, uncontrolled hypertension (SBP>150 or DBP>90)
- History of Kidney and/or liver failure (including transplant) or problems (e.g., cirrhosis); current liver disease or impairment.
- History or current diagnosis of hepatitis.
- Liver function tests more than 20% outside of the normal range.
- Allergies to the study medication, tolcapone (Tasmar).
- History of severe, uncontrolled muscle movements (e.g., uncontrolled jerking, twitching) or a certain severe muscle problem (rhabdomyolysis).
- Experience of dizziness or lightheadedness upon standing on a regular basis (i.e., daily).
- Genetic Profile
- Individuals with the heterozygous genotype (val/met) on the catechol-methyl transferase (COMT) gene. (Note: this is a small pilot study comparing effects of Tolcapone on cognitive performance between val/val (n=8) individuals.) Future research done at our center will plan to include those carrying the val/met genotype.
- Individuals with the homozygous genotype, met/met, on the COMT gene. As of December 2008, the study has accrued 8 met/met participants. To balance the genotype groups, the study will recruit an equal number of participants with the val/val genotype on the COMT gene and not include any further participants with the homozygous, met/met genotype. Future research done at our center will plan to include those carrying the met/met genotype.
- Non-European ancestry as determined by self report at initial telephone screening; we expect there to be ethnic differences in allele frequencies for COMT; therefore, as of December 2008, to reduce ethnic admixture that could bias the genetic analysis of this small sample, the study will be restricted to individuals of European ancestry. All participants of non-European ancestry will be referred to other studies at our center.
- General Exclusion
- Any medical condition or concomitant medication that could compromise participant safety or treatment, as determined by the Principal Investigator and/or Study Physician.
- Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Pilot Study of Tolcapone Effects on Abstinence-Induced Cognitive Symptoms in Smokers
The goals of this within-subject pilot study are: (1) assess the feasibility and safety of administering the Catechol-O-Methyl-Transferase (COMT) inhibitor, tolcapone, to smokers, and (2) explore whether tolcapone may reduce abstinence-induced cognitive and affective symptoms that promote relapse. A secondary exploratory goal is to assess whether these effects may be more pronounced in smokers who carry a high risk COMT genotype for smoking relapse: COMT val/val.
Read the detailed description
Despite decades of research to develop pharmacotherapies for nicotine dependence (ND), with current FDA approved medications (bupropion, varenicline and NRTs) the majority (>60%) of smokers relapse in the first year following treatment (Lerman, Patterson et al. 2005; Tonstad, Tonnesen et al. 2006). Testing novel medications that may reduce abstinence symptoms that prompt smoking relapse is a plausible route to identifying new treatments for nicotine dependence. The goals of this within-subject pilot study are: (1) assess the feasibility and safety of administering the Catechol-O-Methyl-Transferase (COMT) inhibitor, tolcapone, to smokers, and (2) explore whether tolcapone may reduce abstinence-induced cognitive and affective symptoms that promote relapse. A secondary exploratory goal is to assess whether these effects may be more pronounced in smokers who carry a high risk COMT genotype for smoking relapse: COMT val/val. Sixteen smokers (8 met/met genotype and 8 val/val genotype) who meet study eligibility criteria will complete two 10-day medication periods: one while taking tolcapone and one while taking placebo (order counterbalanced). The testing session will occur on day 7 of each medication phase and include three computerized tasks. Participants will be asked to refrain from smoking for at least 14 hours (overnight) prior to the testing day in each medication phase. There will be a 3-day medication taper on days 8-10 of each medication period, followed by a washout period of at least 7 days between medication periods. The main outcomes to be evaluated are participant enrollment and retention, side effects, and performance on computerized tasks. Positive results from this pilot study would provide a basis for a larger scale investigation to assess the efficacy of tolcapone as a medication that ameliorates abstinence induced neurocognitive symptoms in smokers.
- Conditions
- Nicotine Dependence
- Being tested
- Tolcapone, Placebo
- Keywords
- Smoking, Abstinence
- Medical subject headings
- Tobacco Use Disorder, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolcaponeDrug
Also called Tasmar
Day 1 100mg three times per day Day 2 - Day 7 200mg three times per day Day 8 200mg twice a day Day 9 200mg once a day Day 10 100mg once a day
PlaceboDrug
Day 1 100mg three times per day Day 2 - Day 7 200mg three times per day Day 8 200mg twice a day Day 9 200mg once a day Day 10 100mg once a day
| Study group | Role | What they receive |
|---|---|---|
| Tolcapone | Active comparator | Tolcapone Receives: Drug: Tolcapone |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Eligible Participants Enrolled Who Completed the Study.
Number of enrolled participants who complete the final study visit
Measured: 30 days
Secondary outcomes (2)
N-back (Working Memory) Correct Reaction Time After Overnight Abstinence.
To obtain preliminary data on the effects of Tolcapone on abstinence-induced neurocognitive deficits in abstinent smokers with differing COMT genotypes. We examined reaction time differences on the n-back task between tolcapone and placebo treatment.
Measured: 30 days
Correct Reaction Time During Attention Task Performance After Overnight Abstinence.
We wanted to examine the effects of Tolcapone on the Continuous Performance Task (attention task) after overnight abstinence as compared to placebo.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2010 (estimated)
- Study startJul 2008
- Primary completionMay 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Caryn Lerman, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01202955
- Sponsor's protocol ID
- 808250
- Status last verified
- Sep 2018
- First submitted
- 19 Aug 2010
- Last updated
- 12 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Tolcapone Effects on Abstinence-Induced Cognitive Symptoms in Smokers
- ClinicalTrials.gov ID
- NCT01202955
- Acronym / sponsor ID
- 808250
- Conditions
- Nicotine Dependence
- Keywords
- Smoking, Abstinence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Jul 2008
- Primary completion
- May 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 16 Sep 2010 (estimated)
- Results
- Posted 22 Apr 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goals of this within-subject pilot study are: (1) assess the feasibility and safety of administering the Catechol-O-Methyl-Transferase (COMT) inhibitor, tolcapone, to smokers, and (2) explore whether tolcapone may reduce abstinence-induced cognitive and affective symptoms that promote relapse. A secondary exploratory goal is to assess whether these effects may be more pronounced in smokers who carry a high risk COMT genotype for smoking relapse: COMT val/val.
Detailed description
Despite decades of research to develop pharmacotherapies for nicotine dependence (ND), with current FDA approved medications (bupropion, varenicline and NRTs) the majority (>60%) of smokers relapse in the first year following treatment (Lerman, Patterson et al. 2005; Tonstad, Tonnesen et al. 2006). Testing novel medications that may reduce abstinence symptoms that prompt smoking relapse is a plausible route to identifying new treatments for nicotine dependence. The goals of this within-subject pilot study are: (1) assess the feasibility and safety of administering the Catechol-O-Methyl-Transferase (COMT) inhibitor, tolcapone, to smokers, and (2) explore whether tolcapone may reduce abstinence-induced cognitive and affective symptoms that promote relapse. A secondary exploratory goal is to assess whether these effects may be more pronounced in smokers who carry a high risk COMT genotype for smoking relapse: COMT val/val. Sixteen smokers (8 met/met genotype and 8 val/val genotype) who meet study eligibility criteria will complete two 10-day medication periods: one while taking tolcapone and one while taking placebo (order counterbalanced). The testing session will occur on day 7 of each medication phase and include three computerized tasks. Participants will be asked to refrain from smoking for at least 14 hours (overnight) prior to the testing day in each medication phase. There will be a 3-day medication taper on days 8-10 of each medication period, followed by a washout period of at least 7 days between medication periods. The main outcomes to be evaluated are participant enrollment and retention, side effects, and performance on computerized tasks. Positive results from this pilot study would provide a basis for a larger scale investigation to assess the efficacy of tolcapone as a medication that ameliorates abstinence induced neurocognitive symptoms in smokers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolcapone | Active comparator | Drug: TolcaponeTolcapone |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy as determined by a responsible physician, based on a medical evaluation including history, physical and psychiatric examination, laboratory tests, liver function monitoring.
- Smokers who are between 18 and 55 years of age and have an IQ greater than 90.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions, listed in the consent form.
- Based upon self-report, subjects must smoke >10 cigarettes/day and be interested in quitting smoking in the next 6 months (i.e., treatment-seekers).
- Women of childbearing potential must consent to using a medically accepted method of birth control (e.g., condoms and spermicide, oral contraceptive, Depo-provera injection, contraceptive patch, tubal ligation).
Key exclusion criteria (45 listed)
- Smoking Behavior
- Use of chewing tobacco or snuff
- Current enrollment or plans to enroll in another smoking cessation program in the next month
- Plan to use other nicotine substitutes or smoking cessation treatments in the next month
- Provide a baseline carbon monoxide (CO) reading < 10ppm
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 |
|---|---|---|
| TolcaponeAlso: TasmarDay 1 100mg three times per day Day 2 - Day 7 200mg three times per day Day 8 200mg twice a day Day 9 200mg once a day Day 10 100mg once a day | Drug | Tolcapone |
| PlaceboDay 1 100mg three times per day Day 2 - Day 7 200mg three times per day Day 8 200mg twice a day Day 9 200mg once a day Day 10 100mg once a day | Drug | Placebo |
Primary outcome
Number of Eligible Participants Enrolled Who Completed the Study.
Time frame: 30 days
Number of enrolled participants who complete the final study visit
2 secondary outcomes
N-back (Working Memory) Correct Reaction Time After Overnight Abstinence.
Time frame: 30 days
Correct Reaction Time During Attention Task Performance After Overnight Abstinence.
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Caryn Lerman, PhD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tolcapone in people with Nicotine Dependence, run by University of Pennsylvania 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 5 inclusion and 45 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 12 Sep 2018. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Eligible Participants Enrolled Who Completed the Study. (time frame: 30 days). 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 12 Sep 2018.