Study of the Effects of Mecamylamine and Varenicline in Schizophrenia

NCT00455650 | Completed Results

• 2 other identifiers: PHRC #2006-P-001361CORRC#3-2007
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cognition in Schizophrenia

Keywords

schizophrenia; cognition; nicotinic receptors; mecamylamine; varenicline

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  Baseline (week 0), week 1, week 2 and week 3 as one time point (see outcome measure description)

Secondary Outcomes (3)

• Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Cognitive Interference as Assessed by The Three-card Stroop Task

  Baseline (week 1), week 2, week 3, week 4 analyzed as a single time point

• Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Sustained Attention as Assessed by The N-back Task

  Baseline (week 1), week 2, week 3, week 4 analyzed as a single time point

• 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

  Baseline (week 1), week 2, week 3, week 4 analyzed as a single time point

Study Arms (6)

Schizophrenia, Mecamylamine

ACTIVE COMPARATOR

Drug: Mecamylamine

Schizophrenia, Varenicline

ACTIVE COMPARATOR

Drug: Varenicline

Schizophrenia, Placebo

PLACEBO COMPARATOR

Drug: Placebo

Control, Mecamylamine

ACTIVE COMPARATOR

Drug: Mecamylamine

Control, Varenicline

ACTIVE COMPARATOR

Drug: Varenicline

Control, placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Mecamylamine DRUG

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.

Also known as: Inversine

Control, Mecamylamine; Schizophrenia, Mecamylamine

Varenicline DRUG

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.

Also known as: Chantix

Control, Varenicline; Schizophrenia, Varenicline

Placebo DRUG

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.

Control, placebo; Schizophrenia, Placebo

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Alliance for Research on Schizophrenia and Depression: collaborator
• The Bowman Family Foundation: collaborator

Study Sites (1)

Freedom Trail Clinic, Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• 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.

  PMID: 24114425 RESULT

MeSH Terms

Conditions

Schizophrenia

Interventions

Mecamylamine; Varenicline

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Norbornanes; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Results Point of Contact

• Title: A. Eden Evins, MD, MPH
• Organization: Massachusetts General Hospital

aeevins@mgh.harvard.edu

617-643-4679

Study Officials

• A. Eden Evins, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Catherine Fullerton, M.D., M.P.H.

  Massachusetts General Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Center for Addiction Medicine

Study Record Dates

• First Submitted: April 2, 2007
• First Posted: April 4, 2007
• Study Start: March 1, 2007
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: March 28, 2017
• Results First Posted: March 28, 2017

Record last verified: 2017-02

Locations

US (1)