Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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: February 7, 2017
Last verified: February 2017
  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
Intervention Model: Crossover Assignment
Masking: Participant, 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:
  • 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.


Secondary Outcome Measures:
  • Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Cognitive Interference as Assessed by The Three-card Stroop Task [ Time Frame: Baseline (week 1), week 2, week 3, week 4 analyzed as a single time point ]
    In the 3-card Stroop Task, 3 cards were presented; the 1st contained color names printed in black ink, the 2nd contained colored patches of ink, the 3rd contained color names printed in incongruously colored ink. Participants were asked to read or name as many items as possible in 45 seconds for each condition. Individuals are asked to identify the color of the ink of a word. They may be distracted by the presence of a word that states another color (i.e. the word "blue" written in green ink would require the answer green).The interference score was calculated by dividing the color-word score by the color score. 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 pbo) 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

  • Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Sustained Attention as Assessed by The N-back Task [ Time Frame: Baseline (week 1), week 2, week 3, week 4 analyzed as a single time point ]
    The N-back task with 1- and 2-back parametric conditions was used. During the task, a letter was displayed for 1,500 ms every 2 s with a 500 ms isi. Participants were asked to press the "1" key for letters that corresponded to the letter 1 back for the 1-back condition, the "2" key for the 2-back condition, and the "3" key for nontarget letters. Outcome variable presented is hit reaction time There is only one outcome measure time point because this outcome was 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.

  • Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Working Memory as Assessed by The Visual Spatial Working Memory (VSWM) Task [ Time Frame: Baseline (week 1), week 2, week 3, week 4 analyzed as a single time point ]
    In the Visual spatial working memory (VSWM), participants were asked to place the cursor where the symbol appeared immediately after its display. For 16 additional trials, participants were asked to identify the symbol location after a 30-second delay. During the delay, participants were distracted by being asked to read aloud words appearing on the screen at 2-second intervals. The outcome of interest in this task were the average distance from the target for immediate and delayed recall There is only one outcome measure time frame because this outcome was 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.


Enrollment: 89
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: Schizophrenia, 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: Schizophrenia, 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: Schizophrenia, 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.
Active Comparator: Control, 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: Control, 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: Control, 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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 68 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
Results First Received: September 22, 2016
Last Updated: February 7, 2017

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

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Varenicline
Mecamylamine
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Ganglionic Blockers
Autonomic Agents
Peripheral Nervous System Agents
Nicotinic Antagonists
Cholinergic Antagonists

ClinicalTrials.gov processed this record on April 25, 2017