Study of the Effects of Mecamylamine and Varenicline in Schizophrenia

This study has been completed.
Sponsor:
Collaborators:
National Alliance for Research on Schizophrenia and Depression
The Bowman Family Foundation
Information provided by (Responsible Party):
A. Eden Evins, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00455650
First received: April 2, 2007
Last updated: November 6, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention
Cognition in Schizophrenia
Drug: Mecamylamine
Drug: Varenicline
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Cognitive Effects of Mecamylamine and Varenicline in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change from baseline reaction time for correct responses on the CPT-IP continuous performance task [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effects of mecamylamine and varenicline compared with placebo in schizophrenia and control groups on response bias, reaction time, errors of commission and errors of omission [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Enrollment: 71
Study Start Date: March 2007
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Mecamylamine Drug: Mecamylamine
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.
Other Name: Inversine
Active Comparator: Varenicline Drug: Varenicline
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.
Other Name: Chantix
Placebo Comparator: Placebo Drug: Placebo
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.

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   18 Years to 68 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for Patients with Schizophrenia:

  • Males or females ages 18-68
  • Axis I diagnosis of schizophrenia or schizoaffective disorder
  • Smoking or Non-smoking
  • Negative salivary screen for drugs of abuse
  • Stable psychiatric treatment for 4 weeks

Exclusion Criteria for Patients with Schizophrenia

  • Current (within the last 6 months) DSM-IV diagnosis of bipolar disorder, PTSD, organic mental disorder, or anorexia nervosa
  • Substance use disorder other than nicotine or caffeine in the past 6 months
  • Orthostatic blood pressure changes at 3 minutes of > 20 mm Hg systolic or 10 mm Hg diastolic
  • Blood Pressure: Women under 50 years of age: Supine baseline systolic blood pressure < 90 mm Hg; Men under 50 years of age: Supine baseline systolic blood pressure < 100 mm Hg; Women and men over 50 years of age: Supine baseline systolic blood pressure < 110 mm Hg
  • History of angina, MI within the past 2 years, CHF with LVEF < 40%
  • History of syncope or neurocardiogenic syncope
  • History of stroke or TIA's
  • Glaucoma
  • Pyloric Stenosis
  • Current pregnancy or lactation
  • Renal Insufficiency/Uremia
  • Known allergy to mecamylamine
  • Inability to give informed consent
  • Cognitive impairment secondary to head injury, dementia, general medical condition, or mental retardation
  • Current use of antibiotics or sulfa drugs, vasodilators such as alpha blocking agents and nitrates
  • Use of investigational medication or device within one month of randomization
  • Chronic use of antihypertensive drugs, including diuretics, will be considered on an individual basis

Inclusion Criteria for Healthy Controls:

  • Males or females ages 18-68
  • Smoking or Non-smoking
  • Negative salivary screen for drugs of abuse

Exclusion Criteria for Healthy Controls:

  • Current or lifetime Axis I DSM-IV diagnosis or family history of schizophrenia, schizoaffective disorder, or bipolar disorder
  • Current (within past 6 months) Axis I DSM-IV diagnosis of major depressive disorder, eating disorder, generalized anxiety disorder or PTSD
  • Substance use disorder other than nicotine or caffeine in the past 6 months
  • Orthostatic blood pressure changes at 3 minutes of > 20 mm Hg systolic or 10 mm Hg diastolic
  • Blood Pressure: Women under 50 years of age: Supine baseline systolic blood pressure < 90 mm Hg; Men under 50 years of age: Supine baseline systolic blood pressure < 100 mm Hg; Women and men over the age of 50: Supine baseline systolic blood pressure < 110 mm Hg
  • History of angina, MI within the past 2 years, CHF with LVEF < 40%
  • History of syncope or neurocardiogenic syncope
  • History of stroke or TIA's
  • Glaucoma
  • Pyloric Stenosis
  • Current pregnancy or lactation
  • Renal Insufficiency/Uremia
  • Known allergy to mecamylamine
  • Inability to give informed consent
  • Cognitive impairment secondary to head injury, dementia, general medical condition, or mental retardation
  • Current use of antibiotics or sulfa drugs, vasodilators such as alpha blocking agents and nitrates
  • Use of investigational medication or device within one month of randomization
  • Chronic use of antihypertensive drugs, including diuretics, will be considered on an individual basis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00455650

Locations
United States, Massachusetts
Freedom Trail Clinic, Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Alliance for Research on Schizophrenia and Depression
The Bowman Family Foundation
Investigators
Principal Investigator: A. Eden Evins, MD, MPH Massachusetts General Hospital
Study Director: Catherine Fullerton, M.D., M.P.H. Massachusetts General Hospital
  More Information

Publications:
Responsible Party: A. Eden Evins, Director of Center for Addiction Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00455650     History of Changes
Other Study ID Numbers: PHRC #2006-P-001361, CORRC#3-2007
Study First Received: April 2, 2007
Last Updated: November 6, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
schizophrenia
cognition
nicotinic receptors
mecamylamine
varenicline

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Varenicline
Mecamylamine
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Ganglionic Blockers
Autonomic Agents
Peripheral Nervous System Agents
Nicotinic Antagonists
Cholinergic Antagonists

ClinicalTrials.gov processed this record on September 18, 2014