|First Submitted Date ICMJE||April 2, 2007|
|First Posted Date ICMJE||April 4, 2007|
|Results First Submitted Date||September 22, 2016|
|Results First Posted Date||March 28, 2017|
|Last Update Posted Date||March 28, 2017|
|Start Date ICMJE||March 2007|
|Primary Completion Date||January 2013 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Prolonged Attention as Assessed With the CPT-IP Hit Reaction Time Variability [ Time Frame: Baseline (week 0), week 1, week 2 and week 3 as one time point (see outcome measure description) ]
The Continuous Performance Test-Identical Pairs, CPT-IP, Version 4.0 was developed and normed for use in people with schizophrenia and normal controls. This task estimates attention by requiring an individual to push a response key when two identical pairs of shapes or numbers are presented in sequence. Stimuli were presented with increasing cognitive load: 2-, 3-, and 4-digit targets. Outcome variables measured included correct hits, hit reaction time (HRT), errors of commission: false alarms and random errors, and the primary outcome, variability, or standard deviation, of hit reaction time, HRT-SD. There is only one outcome measure time point because cognitive outcomes were analyzed using crossover analyses of covariance (ANCOVA) with drug (mecamylamine vs. varenicline vs. placebo) as a within subject factor, diagnosis (schizophrenia vs. control) as a between subject factor, as well as study period and drug administration sequence as between subject crossover design factors.
|Original Primary Outcome Measures ICMJE
||The primary outcome measure is the change from baseline reaction time for correct responses on the CPT-IP continuous performance task.|
|Change History||Complete list of historical versions of study NCT00455650 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
||Secondary outcome measures include effect of mecamylamine compared with placebo in schizophrenia and control groups on response bias in the signal detection task, reaction time, errors of commission and errors of omission on the CPT-IP|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study of the Effects of Mecamylamine and Varenicline in Schizophrenia|
|Official Title ICMJE||Cognitive Effects of Mecamylamine and Varenicline in Schizophrenia|
We are conducting this study to find out if blocking or partially stimulating the effects of nicotine in the brain can affect memory and concentration. Nicotine is the addictive drug found in tobacco products. Our subjects will be people with and without mental illness (schizophrenia), smokers and non-smokers.
We will use a medication called mecamylamine (Inversine) to block the effects of nicotine on the brains of our subjects. We will also use a medication called varenicline (Chantix) to partially increase the effects of nicotine on the brains of our subjects. This study also uses a placebo, a pill that does not have any active ingredients but looks exactly like the mecamylamine and varenicline pills. We will compare the effects of giving mecamylamine or placebo to people who have schizophrenia and people who do not have schizophrenia.
We know that people with schizophrenia smoke heavily and find it harder to stop smoking than most other people do. Studies have shown that people with schizophrenia may smoke more because nicotine helps their concentration and memory. We are interested in helping people with schizophrenia smoke less. Mecamylamine blocks the parts of the brain that react to nicotine and varenicline partially stimulates and partially blocks the parts of the brain that react to nicotine. Both medications may decrease the effects that smoking has on the body.
Taking part in this study will involve one Screening Visit and four Study Visits, all of which will take part over a period of about 3-5 weeks.
SCREENING VISIT We will ask you to come to the Freedom Trail Clinic of Massachusetts General Hospital for a Screening Visit. If you agree to take part in the study, a member of the study staff will explain the study to you and ask you to sign a consent form. You will then have an interview with a study staff member.
We will ask you questions about your current and past mental health and any symptoms you have experienced, such as hearing voices. We will ask you about previous smoking and your current medications. We will review your medical record for psychiatric diagnosis and treatment. Although we hope you will answer all the questions we ask, you may skip over any you choose not to answer. Your answers will be kept confidential.
We will also give you a physical examination. A doctor will fully examine you, including listening to your heart and lungs and feeling your abdomen (belly area). We will also weigh you and take your blood pressure and pulse.
We will need to take a sample of your breath to check for recent smoking. We take this sample by asking you to breathe into a small, hand-held machine. This machine measures a gas in your breath (carbon monoxide) and tells us how much you smoke.
We will ask you for a saliva sample, to check for the use of nicotine and commonly used street drugs, such as marijuana, cocaine, PCP, opiates or amphetamines. We do this by asking you to put a small sponge in your mouth. The sponge soaks up a small sample of saliva. If you test positive for any of these street drugs, you will not be able to take part in the study. The results of the saliva test will not become part of your medical record, but will be recorded in the study records.
If you qualify for the study, we will arrange a date and time for you to return for the first of four study visits. The four visits will be separated by approximately one week. You will continue to take all your regular medications during this study, unless instructed otherwise by a study physician.
FIRST STUDY VISIT The first visit will last about 2½ hours in total. At this visit, you will practice the computer tasks included in the study until you are comfortable with them. These tasks measure your concentration and memory. You do not need to know how to use a computer to do these tasks. They will take about 1½ hours in total to finish.
In one task, we will ask you to watch the screen very closely and press a button every time you see a certain combination of numbers. In another task, we will ask you to remember a letter or word and press the button when you see it again. In another task, you will need to remember the location of a cross and indicate to the location after a period of time. In another task, we will ask you to read words or colors off of a card.
We will also ask you to fill out some questionnaires about your mood and other psychiatric symptoms. These questionnaires take about 20-30 minutes to complete. Although we hope you will answer all the questions, you may skip over any questions that you don't choose to answer. Your answers will be kept confidential. These questionnaires are labeled with a number, and your name does not appear on them. The code that links numbers to names is kept in a locked cabinet in a different location. Your initials will appear on questionnaires.
During the computer tasks, you will be allowed to take smoking breaks or rest breaks if you need to.
TAKING THE STUDY DRUG OR PLACEBO You will receive mecamylamine one time, varenicline one time, and placebo one time during the course of this study, but on different study days. At the second, third, and fourth visits, you will take one of the study drugs or the placebo, but not both. The order in which you take the medication or placebo will be assigned by chance, like the flip of a coin. Neither study staff nor you will know if you have received medication or placebo, although we can find this out in an emergency.
SECOND, THIRD AND FOURTH STUDY VISITS At these next three study visits, we will ask you to take a pill that either contains mecamylamine (10 mg), varenicline (1 mg), or placebo (no active medications). Prior to giving you the pill, we will again ask for a saliva sample to test for nicotine and commonly used street drugs. You will then relax and watch a movie for three hours. We will provide a selection of DVDs for you to choose from and ask that you choose from among this selection. We will provide food, drinks, and snacks, and you will have a comfortable room to sit in. If you prefer to bring your own food, you may do that as well. During this time we will take your blood pressure and pulse every 30 minutes and ask you to fill out a standard questionnaire that asks about side effects that will take 1-2 minutes.
After 3 hours, we will ask you to provide 3 tablespoons of your blood so that we can measure the amount of study medication in your blood. We will destroy your blood sample at the end of the study. You may choose not to have your blood drawn, and you may still participate in the study.
We will then ask you to complete the same tests and questionnaires that you did during the first study visit, and one additional task in which you will be able to earn extra money during each visit. This additional test is a game on the computer called the "face game."
These computer tasks and questionnaires will take about 2 to 2 ½ hours in total to complete. During this time, you will be able to take breaks to relax or smoke between tasks if needed.
ADDITIONAL TASK AT THE END OF THE SECOND STUDY VISIT ONLY During the second visit after the completion of the normal study tasks, we will ask you to do one additional task, which gives you the opportunity to win money. In this task we will ask you to sort cards into three different piles. You will be given the money you have won as you leave the research center that day.
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Condition ICMJE||Cognition in Schizophrenia|
|Publications *||Roh S, Hoeppner SS, Schoenfeld D, Fullerton CA, Stoeckel LE, Evins AE. Acute effects of mecamylamine and varenicline on cognitive performance in non-smokers with and without schizophrenia. Psychopharmacology (Berl). 2014 Feb;231(4):765-75. doi: 10.1007/s00213-013-3286-3. Epub 2013 Oct 11.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||January 2013|
|Primary Completion Date||January 2013 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Inclusion Criteria for Patients with Schizophrenia:
Exclusion Criteria for Patients with Schizophrenia
Inclusion Criteria for Healthy Controls:
Exclusion Criteria for Healthy Controls:
|Ages||18 Years to 68 Years (Adult, Senior)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00455650|
|Other Study ID Numbers ICMJE||PHRC #2006-P-001361
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||A. Eden Evins, Massachusetts General Hospital|
|Study Sponsor ICMJE||Massachusetts General Hospital|
|PRS Account||Massachusetts General Hospital|
|Verification Date||February 2017|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP