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Effects of Transdermal Nicotine on Response Inhibition to Emotional Cues in Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03838484
Recruitment Status : Active, not recruiting
First Posted : February 12, 2019
Last Update Posted : April 16, 2020
Sponsor:
Collaborators:
National Institute of Mental Health (NIMH)
University of Florida
Information provided by (Responsible Party):
Alan Lewis, Vanderbilt University Medical Center

Brief Summary:
The purpose of this study is to test whether nicotine, a drug that activates receptors called nicotinic acetylcholine receptors in the brain, improves the ability to make or withhold responses to faces that are either emotionally neutral or emotionally negative. This study will also test whether the drug affects brain activity while making or withholding responses using electroencephalography. Previous studies in people with schizophrenia have shown that more errors in response to negative emotional cues are related to greater likelihood of impulsive aggressive behavior. Therefore, the aim of this study is to determine whether nicotine might be a new strategy to reduce aggressive behavior. The investigators' goal is 25 individuals with schizophrenia and 25 healthy controls to complete the study at Vanderbilt.

Condition or disease Intervention/treatment Phase
Schizophrenia Impulsive Behavior Drug: Nicotine Patch, 7 Mg/24 Hr Drug: Placebo patch Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Transdermal Nicotine on Response Inhibition to Emotional Cues in Schizophrenia
Actual Study Start Date : May 10, 2019
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: Healthy: placebo first, nicotine last
Healthy controls will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.
Drug: Nicotine Patch, 7 Mg/24 Hr
Nicotine patch, 7 mg/24 hour will be applied to the skin.

Drug: Placebo patch
Placebo skin patch will be applied to the skin.

Experimental: Healthy: nicotine first, placebo last
Healthy controls will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.
Drug: Nicotine Patch, 7 Mg/24 Hr
Nicotine patch, 7 mg/24 hour will be applied to the skin.

Drug: Placebo patch
Placebo skin patch will be applied to the skin.

Experimental: SCZ: placebo first, nicotine last
Subjects with schizophrenia (SCZ) will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.
Drug: Nicotine Patch, 7 Mg/24 Hr
Nicotine patch, 7 mg/24 hour will be applied to the skin.

Drug: Placebo patch
Placebo skin patch will be applied to the skin.

Experimental: SCZ: nicotine first, placebo last
Subjects with schizophrenia (SCZ) will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.
Drug: Nicotine Patch, 7 Mg/24 Hr
Nicotine patch, 7 mg/24 hour will be applied to the skin.

Drug: Placebo patch
Placebo skin patch will be applied to the skin.




Primary Outcome Measures :
  1. False alarm error rate [ Time Frame: Week 1 ]
    Rate of incorrect responses during NoGo trials

  2. False alarm error rate [ Time Frame: Week 2 ]
    Rate of incorrect responses during NoGo trials

  3. Omission error rate [ Time Frame: Week 1 ]
    Rate of incorrect non-responses during Go trials

  4. Omission error rate [ Time Frame: Week 2 ]
    Rate of incorrect non-responses during Go trials

  5. Reaction time for correct hits [ Time Frame: Week 1 ]
    Time taken from stimulus presentation to button push during Go trials

  6. Reaction time for correct hits [ Time Frame: Week 2 ]
    Time taken from stimulus presentation to button push during Go trials

  7. Reaction time for false alarms [ Time Frame: Week 1 ]
    Time taken from stimulus presentation to button push during NoGo trials

  8. Reaction time for false alarms [ Time Frame: Week 2 ]
    Time taken from stimulus presentation to button push during NoGo trials


Secondary Outcome Measures :
  1. P3 amplitude [ Time Frame: Week 1 ]
    P3 event-related potential amplitude during correct Go trials

  2. P3 amplitude [ Time Frame: Week 2 ]
    P3 event-related potential amplitude during correct Go trials

  3. N2 amplitude [ Time Frame: Week 1 ]
    N2 event-related potential amplitude during correct Go trials

  4. N2 amplitude [ Time Frame: Week 2 ]
    N2 event-related potential amplitude during correct Go trials

  5. N2 amplitude [ Time Frame: Week 1 ]
    N2 event-related potential amplitude during incorrect Go trials

  6. N2 amplitude [ Time Frame: Week 2 ]
    N2 event-related potential amplitude during incorrect Go trials

  7. P3 amplitude [ Time Frame: Week 1 ]
    P3 event-related potential amplitude during incorrect Go trials

  8. P3 amplitude [ Time Frame: Week 2 ]
    P3 event-related potential amplitude during incorrect Go trials

  9. N2 amplitude [ Time Frame: Week 1 ]
    N2 event-related potential amplitude during correct NoGo trials

  10. N2 amplitude [ Time Frame: Week 2 ]
    N2 event-related potential amplitude during correct NoGo trials

  11. P3 amplitude [ Time Frame: Week 1 ]
    P3 event-related potential amplitude during correct NoGo trials

  12. P3 amplitude [ Time Frame: Week 2 ]
    P3 event-related potential amplitude during correct NoGo trials

  13. N2 amplitude [ Time Frame: Week 1 ]
    N2 event-related potential amplitude during incorrect NoGo trials

  14. N2 amplitude [ Time Frame: Week 2 ]
    N2 event-related potential amplitude during incorrect NoGo trials

  15. P3 amplitude [ Time Frame: Week 1 ]
    P3 event-related potential amplitude during incorrect NoGo trials

  16. P3 amplitude [ Time Frame: Week 2 ]
    P3 event-related potential amplitude during incorrect NoGo trials


Other Outcome Measures:
  1. Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale autonomic subscale score [ Time Frame: Week 1 ]
    The UKU side effect rating scale is designed to quantify the side effects of psychotropic drugs and will be used for standard rating of autonomic side effects experienced by subjects in response to study medication. The scale is patient-completed and asks to rate a specific side effect, with scores from 0 (not experienced at all) to 3 (severe levels or degree of the specific side effect). The scores for the autonomic subscale will be added together to create a single total subscale score. The overall range for the autonomic subscale is 0 (no side effects at all) to 33 (severe degree of all queried side effects).

  2. Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale autonomic subscale score [ Time Frame: Week 2 ]
    The UKU side effect rating scale is designed to quantify the side effects of psychotropic drugs and will be used for standard rating of autonomic side effects experienced by subjects in response to study medication. The scale is patient-completed and asks to rate a specific side effect, with scores from 0 (not experienced at all) to 3 (severe levels or degree of the specific side effect). The scores for the autonomic subscale will be added together to create a single total subscale score. The overall range for the autonomic subscale is 0 (no side effects at all) to 33 (severe degree of all queried side effects).



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for schizophrenia subjects:

  1. Men and women age 18 - 65.
  2. Communicative in English.
  3. Provide voluntary, written informed consent.
  4. Physically healthy by medical history,and ECG examination.
  5. BMI > 17.5 and < 45.
  6. Diagnosis of schizophrenia (ICD-10 F20) or schizoaffective disorder (ICD-10 F25) confirmed by Structured Clinical Interview for Diagnostic and Statistical Manual (DSM)-V (SCID) or diagnostic interview with a trained clinician.
  7. Stable medication regimen over at least the past two weeks, including the use of either an oral or intramuscular administration of an antipsychotic medication. Additionally, subjects may take any prescribed medication aside from a nicotine-containing product as long as it has been regularly taken over the past two weeks, including as-needed ("PRN") medication.
  8. Negative urine toxicology and negative urine cotinine (to confirm no recent nicotine use) at screening.
  9. Does not meet criteria for substance or alcohol use disorder per the SCID over the past 6 months
  10. For females, no longer of child-bearing potential, or agreeing to practice effective contraception during the study (e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device [IUD] or intrauterine system [IUS]; barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository; male partner sterilization; or true abstinence when this is in line with the preferred and usual lifestyle of the subject); and,
  11. For females of child-bearing potential, must have negative urine pregnancy test at time of screening visit and before each testing day.
  12. Not breastfeeding/nursing at time of screening or at any time during the study.

Exclusion Criteria for schizophrenia subjects:

  1. Age less than 18 or greater than 65.
  2. Not communicative in English.
  3. Unable to provide written informed consent.
  4. Active suicidal ideation or suicidal behavior.
  5. Current, unstable medical or neurological illness or significant abnormality on ECG.
  6. History of severe head trauma.
  7. BMI < 17.5 or > 45.
  8. History of allergy to transdermal patches.
  9. Screening visit resting heart rate > 110 or < 50 beats per minute, or known history of clinically significant cardiac rhythm abnormalities.
  10. Screening visit systolic blood pressure > 160 or < 90, or diastolic blood pressure > 95 or < 50.
  11. Positive urine toxicology or positive urine cotinine during screening.
  12. Meets criteria for diagnosis of substance or alcohol use disorder by SCID within the past 6 months.
  13. Reports any tobacco smoking or nicotine use over the past month.
  14. Not taking an antipsychotic medication.
  15. Positive urine pregnancy test at time of screening, before each testing day, or any potential concern for pregnancy at any time during the study
  16. Breastfeeding/nursing at time of screening or at any time during the study.

Inclusion Criteria for healthy volunteer subjects:

All of the above except for subjects will be psychiatrically healthy and not taking psychotropic or potentially psychoactive prescription medication.

Exclusion Criteria for healthy volunteer subjects:

All of the above and in addition:

  1. Current use of psychotropic or potentially psychoactive prescription medication.
  2. Major psychiatric disorder as determined by DSM-5 (schizophrenia, major depression, bipolar disorder, obsessive-compulsive disorder, post-traumatic stress disorder, etc.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03838484


Locations
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United States, Tennessee
Vanderbilt Psychiatric Hospital
Nashville, Tennessee, United States, 37212
Sponsors and Collaborators
Vanderbilt University Medical Center
National Institute of Mental Health (NIMH)
University of Florida
Investigators
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Principal Investigator: Alan S Lewis, MD, PhD Vanderbilt University Medical Center
  Study Documents (Full-Text)

Documents provided by Alan Lewis, Vanderbilt University Medical Center:
Informed Consent Form  [PDF] October 23, 2019

Publications:
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Responsible Party: Alan Lewis, Assistant Professor of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT03838484    
Other Study ID Numbers: 190021
7K23MH116339 ( U.S. NIH Grant/Contract )
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: April 16, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Alan Lewis, Vanderbilt University Medical Center:
Nicotine
Nicotinic acetylcholine receptors
Schizophrenia
Schizoaffective disorder
Healthy control
Impulsive behavior
Aggression
Urgency
Additional relevant MeSH terms:
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Schizophrenia
Impulsive Behavior
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action