The Effect of Nicotine on Arousal, Cognition and Social Cognition in Schizophrenic Patients

This study has been completed.
Sponsor:
Collaborator:
Agentschap voor Innovatie door Wetenschap en Technologie
Information provided by:
Janssen Pharmaceutica N.V., Belgium
ClinicalTrials.gov Identifier:
NCT01186471
First received: August 19, 2010
Last updated: March 19, 2012
Last verified: March 2012
  Purpose

This study in patients with stable schizophrenia will investigate the effect of nicotine on arousal, cognitive task and social cognition after acute dose administration.


Condition Intervention Phase
Schizophrenia
Cognition Disorders
Other: A643 (nicotine)
Drug: placebo
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: A Double-Blind, Placebo-Controlled, Randomized Three-Way Crossover Study to Investigate The Effect of Nicotine on Arousal, Standard Cognitive Tasks And Social Cognition in Patients With Schizophrenia (Smoking and Non-Smoking)

Resource links provided by NLM:


Further study details as provided by Janssen Pharmaceutica N.V., Belgium:

Primary Outcome Measures:
  • Event related potentials (P50, P300, N100) and measures of standard cognition and social cognition [ Time Frame: 1 hour post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Nicotine exposure [ Time Frame: predose and 5 min post each dosing ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: May 2010
Study Completion Date: March 2011
Arms Assigned Interventions
Experimental: 001
A643 (nicotine) 1mg oromucosal nicotine spray- three times daily during each treatment period
Other: A643 (nicotine)
1mg oromucosal nicotine spray- three times daily during each treatment period
Experimental: 002
A643 (nicotine) 2mg oromucosal nicotine spray- three times daily during each treatment period
Other: A643 (nicotine)
2mg oromucosal nicotine spray- three times daily during each treatment period
Placebo Comparator: 003
placebo placebo - three times daily during each treatment period
Drug: placebo
placebo - three times daily during each treatment period

Detailed Description:

This is a double-blind (neither physician nor patient knows the name of the assigned drug), placebo-controlled, randomized (study drug assigned by chance), three-way-crossover trial (patients may receive different interventions sequentially during the trial) in patients with stable schizophrenia. The three-way-crossover treatment phase will consist of three blinded treatment periods separated by a wash out period (the period allowed for the entire administered drug to be eliminated from the body) of 2 to 7 days. The study duration for each patient will be approximately 8 weeks. Each patient enrolled will be randomized to receive Treatment A (1mg nicotine per dosing), Treatment B (2mg nicotine per dosing) or Treatment C (placebo) during one of their treatment period. The study drug (nicotine or placebo) will be administered three times daily on Day 1 of each treatment phase as a mouth spray, separated 2 to 3 hours from each other (i.e. 0h; and 2 to 3h; and 4 to 6h post first dosing). Three different blocks of cognitive assessments will follow, one after each drug administration. Safety evaluations include adverse event monitoring, vital signs and clinical laboratory tests. Each patient participating will receive 3 identical study drug administrations per dosing day (2 to 3 hours from each other), resulting in an overall dose of 3 mg nicotine (Treatment A), 6 mg nicotine (Treatment B) or 0 mg nicotine (Treatment C) per dosing day. By the end of the study, after the 3-way crossover, each patient will have received 9 mg nicotine via mouth spray.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • In- or outpatients with schizophrenia stably treated (same primary medication) for at least 2 months with antipsychotic therapy (treatment with more than 1 antipsychotic drug is acceptable provided dose levels have been stable for > 2 months). Fluctuations in dose levels of the primary antipsychotic treatment are acceptable provided the dose levels remain constant as from 2 weeks prior to dosing
  • A known (by the site) disease history of at least 12 months
  • DSM-IV criteria for Schizophrenia
  • Willing to be hospitalized during the treatment periods of the study
  • Body mass index (BMI) between 18 and 35 kg/m2, inclusive (BMI = weight/height2)
  • Women must be: postmenopausal (for at least 12 months), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent (at the discretion of the investigator/per local regulations), or if sexually active, be practicing a highly effective method of birth control and must agree to continue to use the same method of contraception throughout the study
  • Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at admission (each study period)
  • Smoking on average a minimum of 15 cigarettes (or equivalent) per day within 6 months prior to study drug administration (only for Cohort 1)

Exclusion Criteria:

  • Female patients who are pregnant or breastfeeding
  • Clinically significant abnormal values for clinical chemistry, hematology or urinalysis at screening. It is expected that laboratory values will generally be within the normal range for the laboratory, though minor deviations, which are not considered to be of clinical significance to the investigator, are acceptable. Values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2 fold ULN will be allowed
  • Clinically significant abnormal physical examination, vital signs or 12-lead ECG at screening
  • A DSM-IV axis I diagnosis other than schizophrenia that has been the focus of treatment or cause of disability in the last 6 months (such as Major Depressive Episode)
  • Evidence of substance dependence other than nicotine (DSM-IV) in the last 6 months
  • History of or current significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, unmanaged high BP, hematological disease, bronchospastic respiratory disease, renal or hepatic insufficiency, Parkinson's disease, infection (HIV, Hepatitis C), or any other illness that the Investigator considers should exclude the subject (Subjects with mild hypertension, lipid abnormalities, diabetes mellitus or thyroid disease are allowed if no significant treatment changes were required in the past 6 months)
  • Use of anti-parkinsonian agents in the past 2 months
  • Suicidal risk (assessed by the investigator), prior attempts to suicide, command hallucinations and / or hopelessness
  • Smoking cigarettes (or equivalents) or the use of nicotine based products within 3 months prior to study drug administration (only for Cohort 2)
  • Current use of any medication for smoking cessation such as nicotine replacement therapy, bupropion or varenicline
  • History of epilepsy or fits or unexplained black-outs
  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: NCT01186471

Sponsors and Collaborators
Janssen Pharmaceutica N.V., Belgium
Agentschap voor Innovatie door Wetenschap en Technologie
Investigators
Study Director: Janssen Pharmaceutica N.V. Clinical Trial Janssen Pharmaceutica N.V.
  More Information

No publications provided

Responsible Party: Clinical Scientist/Director, Experimental Medicine, Janssen Pharmaceutica N.V., Belgium
ClinicalTrials.gov Identifier: NCT01186471     History of Changes
Other Study ID Numbers: CR017263
Study First Received: August 19, 2010
Last Updated: March 19, 2012
Health Authority: Belgium: Ministry of Social Affairs, Public Health and the Environment

Keywords provided by Janssen Pharmaceutica N.V., Belgium:
Symptomatic treatment
Cognition
Cognitive deficits
Schizophrenia

Additional relevant MeSH terms:
Cognition Disorders
Schizophrenia
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Nicotine
Autonomic Agents
Cholinergic Agents
Cholinergic Agonists
Ganglionic Stimulants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Nicotinic Agonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014