Study of the Effects of Mecamylamine and Varenicline in Schizophrenia
Condition: Cognition in Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Mecamylamine; Varenicline; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): A single dose of 10 mg of mecamylamine (via two 5 mg capsules) is given at the start of the mecamylamine arm of the study. This is the only administration of mecamylamine given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.; A single dose of 1 mg of varenicline (via two 0.5 mg capsules) is given at the start of the varenicline arm of the study. This is the only administration of varenicline given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.; The placebo contains no active medication. The placebo dose is given via two capsules at the start of the placebo arm of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. The placebo has no effects that last for any duration of time.
Other intervention name(s): Inversine; Chantix
Intervention MeSH terms: Mecamylamine; Varenicline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: schizophrenia; cognition; nicotinic receptors; mecamylamine; varenicline