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The Effects of Nicotine on Cognition in Schizophrenia

Primary Purpose

Schizophrenia

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

transdermal nicotine patch

Transdermal Nicotine Patch

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring cognition, nicotine, schizophrenia

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Patients:

DSM IV diagnosis of schizophrenia,
age 18 - 60 inclusive,
able to provide informed consent,
treated with antipsychotic medications at a stable dose for at least 4 weeks,
not treated with an investigational medication in the past 30 days,
WRAT-3 IQ raw score greater than or equal to 35,
non smokers for more than 3 months*,
normal or corrected to normal vision.

Non Smoking defined by:

Self report of not smoking a single cigarette in the past 3 months.
Salivary Cotinine level < 30 ng/ml at screening and on the day of testing
Expired air CO < 9ppm on the day of the testing

Inclusion Criteria:

Control Group:

Age 18 - 60 inclusive,
able to provide informed consent,
not treated with an investigational medication in the past 30 days,
WRAT-3 IQ raw score greater than or equal to 35,
non smokers for more than 3 months*,
normal or corrected to normal vision,
Non Smoking as defined above.

Exclusion Criteria:

Patients:

Use of any nicotine containing product in the past 3 months by self report,
use of cholinesterase inhibitors such as galantamine in the past 3 months,
untreated ischaemic heart disease,
uncontrolled hypertension,
current unstable serious medical illness (renal, neoplastic, hematological),
allergy to patches.
Currently or planning to be pregnant in the next 8 weeks, as verified by positive pregnancy test, or childbearing potential and not using adequate contraception. Those not of childbearing potential include post-menopausal, surgically sterilized, and male participants.
Substance abuse in the past month: self-reported, diagnosed during chart review, and verified by a positive salivary test for cotinine, cocaine, methamphetamine, amphetamine, ethanol, TCH, opiates or PCP at screen.
Recent deterioration in mental state, current major depressive disorder, history of cognitive impairment secondary to other disorders such as head injury, dementia, general medical condition, diagnosis of mental retardation

Exclusion criteria:

Controls:

Past or present DSM IV diagnosis of schizophrenia, schizoaffective disorder, major depression, bipolar disorder, or mental retardation.
First degree relative with diagnosis of schizophrenia or schizoaffective disorder,
use of cholinesterase inhibitors such as galantamine in the past 3 months,
untreated ischaemic heart disease,
uncontrolled hypertension,
current unstable serious medical illness (renal, neoplastic, hematological,)
allergy to patches,
currently or planning to be pregnant in the next 8 weeks, as verified by positive pregnancy test, or childbearing potential and not using adequate contraception. Those not of childbearing potential include post-menopausal, surgically sterilized, and male participants.
Substance abuse in the past month: self-reported, diagnosed during chart review, and verified by a positive salivary test for cotinine, cocaine, methamphetamine, amphetamine, ethanol, TCH, opiates and PCP at screen.
History of cognitive impairment secondary to other disorders such as head injury, dementia, general medical condition

Sites / Locations

Massachusetts General Hospital Schizophrenia Research Program

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Nicotine Patch

Placebo Nicotine Patch

Arm Description

Outcomes

Primary Outcome Measures

Effects of Nicotine Patch Compared With Placebo in Non- Smokers With Schizophrenia and Control Groups on Attention Measured by the Continuous Performance Test Identical Pairs Version

The primary outcome measure was attention as measured by the Continuous Performance Test Identical Pairs (CPT-IP) Version 4.0 (Biobehavioral Technologies, New York, USA), developed for use in patients with schizophrenia and normal controls. In this task, participants were asked to respond when two identical pairs of numbers were presented in sequence by pressing a mouse key as quickly as possible using the dominant hand.The stimuli were presented with increasing cognitive load in successive blocks: two-,three- and four-digit target in the first, second and third block, respectively. Hit reaction time, a standard outcome variables on the CPTIP, is presented here. It was measured 3 hrs after application of the patch

Secondary Outcome Measures

Effects of Nicotine Patch Compared With Placebo in Non- Smokers With Schizophrenia and Control Groups on Visual Attention and Cognitive Interference as Measured by Three Card Stroop

This standard test of visual attention, processing speed and cognitive interference was performed, in which three cards (Stoelting Co., Wood Dale, IL, USA) were presented in order: the first card with color names, the second with colored patches of ink and the third with color namesprinted in incongruously colored ink. Participants were asked to read or name as many colors as possible in 45 s for each condition. The raw interference score was calculated by subtracting the predicted color-word score (calculated using raw word and color scores) from the observed raw color-word score. This value was converted to an interference T score by referring to a standardized table. A higher interference T score indicates better task performance with less interference. It was measured 3 hrs after application of the patch, after CPT

Effects of Nicotine Patch Compared With Placebo in Non- Smokers With Schizophrenia and Control Groups on Letter Number Sequencing

This measure of working memory and auditory attention was performed under two conditions. In the first condition, participants were read progressively longer lists of letters and numbers and instructed to repeat these exactly as given, without reordering. In the second condition, participants were read progressively longer lists of numbers and letters and instructed to re-order the list and give the numbers first in ascending order and then the letters in alphabetical order (WMS-III). The sum of the trial scores provided the item score and the sum of the item scores provided the total score.It was measured 3 hrs after application of the patch, after CPT and Stroop. The total score ranges from 0 to 21.Higher scores of Letter number sequencing means better working memory and auditory attention

Effects of Nicotine Patch Compared With Placebo in Non- Smokers With Schizophrenia and Control Groups on Lateralized Psychomotor Speed Measured by the Grooved Pegboard

The Grooved Pegboard (model 32025 Lafayette Instrument Company, Lafayette, IN, USA). In this test of lateralized psychomotor speed, participants had 45 s to place as many pegs as possible into grooves on a board using their dominant hand. The number of correctly placed pegs were recorded for each of the two trials.It was measured 3 hrs after application of the patch after CPT, Stroop and Letter number sequencing

Full Information

NCT ID

NCT00383747

First Posted

September 29, 2006

Last Updated

March 20, 2017

Sponsor

Massachusetts General Hospital

Collaborators

Stanley Medical Research Institute, North Suffolk Mental Health Association

1. Study Identification

Unique Protocol Identification Number

NCT00383747

Brief Title

The Effects of Nicotine on Cognition in Schizophrenia

Official Title

A Double Blind Placebo Controlled Trial of the Effects of Transdermal Nicotine on Cognitive Function in Non-Smokers With and Without Schizophrenia

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

April 2004 (undefined)

Primary Completion Date

January 2009 (Actual)

Study Completion Date

January 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

Stanley Medical Research Institute, North Suffolk Mental Health Association

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Patients with schizophrenia have a variety cognitive deficits and nicotine has been shown to normalize some of these deficits. The purpose of this study is to investigate the effects of nicotine on cognition in schizophrenia.We will evaluate the effects of transdermal nicotine compared with placebo for attentional impairments in non-smokers with schizophrenia and controls.

Detailed Description

We propose to test the efficacy and safety of transdermal nicotine for attention and working memory in outpatients with stable symptoms of schizophrenia treated with high potency antipsychotic medications that do not smoke cigarettes or use nicotine-containing products. This is a randomized, double-blind, placebo-controlled pilot study to determine whether transdermal nicotine, initiated in a clinic setting and dosed for four hours is safe and effective for improving attention and spatial working memory deficits in patients with schizophrenia. This is an add-on study, subjects will continue with their usual medications and treatments throughout. Subjects are 30- non-smoking outpatients with stable treated schizophrenia and 30 normal controls who do not have a major mental illness and who are matched for age sex and parental education. Subjects are randomized to one of 2 groups for order of receiving active and placebo patch, using a computer generated random number sequence. Randomization is concealed using opaque envelopes. Assessors and subjects are blind to group allocation. The primary outcome measure is d' measure on the CPT-IP following a 4 hour administration of the transdermal nicotine patch. Secondary outcome measures are performance on tasks assessing attention, numeric and visuospatial working memory, psychomotor ability, executive functioning and motivation for reward following nicotine patch administration. Specific Aims To evaluate the effectiveness of transdermal nicotine compared with placebo for attentional impairment in patients with schizophrenia Hypothesis 1.1: Subjects will demonstrate greater signal detection as measured by the d' (hits vs. false alarms) on the Continuous Performance Test Identical Pairs Version (CPT-IP) following 4-hour nicotine administration when compared with placebo administration. Hypothesis 1.2: Subjects will demonstrate decreased false alarms on the CPT-IP following 4-hour nicotine administration when compared with placebo administration. Hypothesis 1.3: Subjects will demonstrate decreased reaction time on the CPT-IP following 4- hour nicotine administration when compared with placebo administration. To evaluate the effect of transdermal nicotine in patients with schizophrenia compared with normal matched controls Hypothesis 2.1: Schizophrenia subjects will demonstrate greater improvement in signal detection as measured by the d' (hits vs. false alarms) on the Continuous Performance test identical pairs version(CPT-IP) following 4-hour nicotine administration when compared with normal controls. Hypothesis 2.2: Schizophrenia subjects will demonstrate greater reduction in false alarms on the CPT-IP following 4-hour nicotine administration when compared with normal controls. Hypothesis 2.3: Schizophrenia subjects will demonstrate decreased reaction time on the CPT-IP following 4- hour nicotine administration when compared with normal controls. Performance Test Identical Pairs Version

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia

Keywords

cognition, nicotine, schizophrenia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nicotine Patch

Arm Type

Active Comparator

Arm Title

Placebo Nicotine Patch

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

transdermal nicotine patch

Other Intervention Name(s)

Nicoderm CQ patch

Intervention Description

14mg transdermal nicotine application

Intervention Type

Drug

Intervention Name(s)

Transdermal Nicotine Patch

Intervention Description

14mg transdermal nicotine application

Primary Outcome Measure Information:

Title

Effects of Nicotine Patch Compared With Placebo in Non- Smokers With Schizophrenia and Control Groups on Attention Measured by the Continuous Performance Test Identical Pairs Version

Description

Time Frame

Visit 1 and visit 2 (separated by an interval of 7-10 days)

Secondary Outcome Measure Information:

Title

Effects of Nicotine Patch Compared With Placebo in Non- Smokers With Schizophrenia and Control Groups on Visual Attention and Cognitive Interference as Measured by Three Card Stroop

Description

Time Frame

Visit 1 and visit 2 (separated by an interval of 7-10 days)

Title

Effects of Nicotine Patch Compared With Placebo in Non- Smokers With Schizophrenia and Control Groups on Letter Number Sequencing

Description

Time Frame

Visit 1 and visit 2 (separated by an interval of 7-10 days)

Title

Effects of Nicotine Patch Compared With Placebo in Non- Smokers With Schizophrenia and Control Groups on Lateralized Psychomotor Speed Measured by the Grooved Pegboard

Description

Time Frame

Visit 1 and visit 2 (separated by an interval of 7-10 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients: DSM IV diagnosis of schizophrenia, age 18 - 60 inclusive, able to provide informed consent, treated with antipsychotic medications at a stable dose for at least 4 weeks, not treated with an investigational medication in the past 30 days, WRAT-3 IQ raw score greater than or equal to 35, non smokers for more than 3 months*, normal or corrected to normal vision. Non Smoking defined by: Self report of not smoking a single cigarette in the past 3 months. Salivary Cotinine level < 30 ng/ml at screening and on the day of testing Expired air CO < 9ppm on the day of the testing Inclusion Criteria: Control Group: Age 18 - 60 inclusive, able to provide informed consent, not treated with an investigational medication in the past 30 days, WRAT-3 IQ raw score greater than or equal to 35, non smokers for more than 3 months*, normal or corrected to normal vision, Non Smoking as defined above. Exclusion Criteria: Patients: Use of any nicotine containing product in the past 3 months by self report, use of cholinesterase inhibitors such as galantamine in the past 3 months, untreated ischaemic heart disease, uncontrolled hypertension, current unstable serious medical illness (renal, neoplastic, hematological), allergy to patches. Currently or planning to be pregnant in the next 8 weeks, as verified by positive pregnancy test, or childbearing potential and not using adequate contraception. Those not of childbearing potential include post-menopausal, surgically sterilized, and male participants. Substance abuse in the past month: self-reported, diagnosed during chart review, and verified by a positive salivary test for cotinine, cocaine, methamphetamine, amphetamine, ethanol, TCH, opiates or PCP at screen. Recent deterioration in mental state, current major depressive disorder, history of cognitive impairment secondary to other disorders such as head injury, dementia, general medical condition, diagnosis of mental retardation Exclusion criteria: Controls: Past or present DSM IV diagnosis of schizophrenia, schizoaffective disorder, major depression, bipolar disorder, or mental retardation. First degree relative with diagnosis of schizophrenia or schizoaffective disorder, use of cholinesterase inhibitors such as galantamine in the past 3 months, untreated ischaemic heart disease, uncontrolled hypertension, current unstable serious medical illness (renal, neoplastic, hematological,) allergy to patches, currently or planning to be pregnant in the next 8 weeks, as verified by positive pregnancy test, or childbearing potential and not using adequate contraception. Those not of childbearing potential include post-menopausal, surgically sterilized, and male participants. Substance abuse in the past month: self-reported, diagnosed during chart review, and verified by a positive salivary test for cotinine, cocaine, methamphetamine, amphetamine, ethanol, TCH, opiates and PCP at screen. History of cognitive impairment secondary to other disorders such as head injury, dementia, general medical condition

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

A E EVINS, MD MPH

Organizational Affiliation

Massachusetts General Hosptal

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital Schizophrenia Research Program

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17443126

Citation

Barr RS, Culhane MA, Jubelt LE, Mufti RS, Dyer MA, Weiss AP, Deckersbach T, Kelly JF, Freudenreich O, Goff DC, Evins AE. The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls. Neuropsychopharmacology. 2008 Feb;33(3):480-90. doi: 10.1038/sj.npp.1301423. Epub 2007 Apr 18.

Results Reference

result

PubMed Identifier

17976537

Citation

Barr RS, Pizzagalli DA, Culhane MA, Goff DC, Evins AE. A single dose of nicotine enhances reward responsiveness in nonsmokers: implications for development of dependence. Biol Psychiatry. 2008 Jun 1;63(11):1061-5. doi: 10.1016/j.biopsych.2007.09.015. Epub 2007 Nov 5.

Results Reference

result

PubMed Identifier

18548234

Citation

Jubelt LE, Barr RS, Goff DC, Logvinenko T, Weiss AP, Evins AE. Effects of transdermal nicotine on episodic memory in non-smokers with and without schizophrenia. Psychopharmacology (Berl). 2008 Jul;199(1):89-98. doi: 10.1007/s00213-008-1133-8. Epub 2008 Jun 12.

Results Reference

result

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The Effects of Nicotine on Cognition in Schizophrenia

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