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

NCT03838484 | Terminated Results

• 2 other identifiers: 1900217K23MH116339
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Impulsive Behavior

Keywords

Nicotine; Nicotinic acetylcholine receptors; Schizophrenia; Schizoaffective disorder; Healthy control; Impulsive behavior; Aggression; Urgency

Outcome Measures

Primary Outcomes (8)

• False Alarm Error Rate

  Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key ("Go") or withhold pressing a key ("NoGo"). The False Alarm Error Rate will be measured by the proportion of incorrect responses.

  Week 1

• False Alarm Error Rate

  Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key ("Go") or withhold pressing a key ("NoGo"). The False Alarm Error Rate will be measured by the proportion of incorrect responses.

  Week 2

• Omission Error Rate

  Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key ("Go") or withhold pressing a key ("NoGo"). The Omission Error Rate will be measured by the proportion of questions asked with a failure to respond.

  Week 1

• Omission Error Rate

  Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key ("Go") or withhold pressing a key ("NoGo"). The Omission Error Rate will be measured by the proportion of questions asked with a failure to respond.

  Week 2

• Reaction Time for Correct Hits

  Time taken from stimulus presentation to button push during Go trials

  Week 1

• Reaction Time for Correct Hits

  Time taken from stimulus presentation to button push during Go trials

  Week 2

• Reaction Time for False Alarms

  Time taken from stimulus presentation to button push during NoGo trials

  Week 1

• Reaction Time for False Alarms

  Time taken from stimulus presentation to button push during NoGo trials

  Week 2

Study Arms (4)

Healthy: placebo first, nicotine last

EXPERIMENTAL

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; Drug: Placebo patch

Healthy: nicotine first, placebo last

EXPERIMENTAL

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; Drug: Placebo patch

SCZ: placebo first, nicotine last

EXPERIMENTAL

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; Drug: Placebo patch

SCZ: nicotine first, placebo last

EXPERIMENTAL

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; Drug: Placebo patch

Interventions

Nicotine Patch, 7 Mg/24 Hr DRUG

Nicotine patch, 7 mg/24 hour will be applied to the skin.

Healthy: nicotine first, placebo last; Healthy: placebo first, nicotine last; SCZ: nicotine first, placebo last; SCZ: placebo first, nicotine last

Placebo patch DRUG

Placebo skin patch will be applied to the skin.

Healthy: nicotine first, placebo last; Healthy: placebo first, nicotine last; SCZ: nicotine first, placebo last; SCZ: placebo first, nicotine last

Eligibility Criteria

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

You may qualify if:

• Men and women age 18 - 65.
• Communicative in English.
• Provide voluntary, written informed consent.
• Physically healthy by medical history,and ECG examination.
• BMI \> 17.5 and \< 45.
• 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.
• 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.
• Negative urine toxicology and negative urine cotinine (to confirm no recent nicotine use) at screening.
• Does not meet criteria for substance or alcohol use disorder per the SCID over the past 6 months
• 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,
• For females of child-bearing potential, must have negative urine pregnancy test at time of screening visit and before each testing day.
• Not breastfeeding/nursing at time of screening or at any time during the study.

You may not qualify if:

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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institute of Mental Health (NIMH): collaborator
• University of Florida: collaborator

Study Sites (1)

Vanderbilt Psychiatric Hospital

Nashville, Tennessee, 37212, United States

Location

Related Publications (3)

• Krakowski MI, De Sanctis P, Foxe JJ, Hoptman MJ, Nolan K, Kamiel S, Czobor P. Disturbances in Response Inhibition and Emotional Processing as Potential Pathways to Violence in Schizophrenia: A High-Density Event-Related Potential Study. Schizophr Bull. 2016 Jul;42(4):963-74. doi: 10.1093/schbul/sbw005. Epub 2016 Feb 19.

  PMID: 26895845 BACKGROUND

• Egashira K, Matsuo K, Nakashima M, Watanuki T, Harada K, Nakano M, Matsubara T, Takahashi K, Watanabe Y. Blunted brain activation in patients with schizophrenia in response to emotional cognitive inhibition: a functional near-infrared spectroscopy study. Schizophr Res. 2015 Mar;162(1-3):196-204. doi: 10.1016/j.schres.2014.12.038. Epub 2015 Jan 13.

  PMID: 25595654 BACKGROUND

• Lewis AS, van Schalkwyk GI, Lopez MO, Volkmar FR, Picciotto MR, Sukhodolsky DG. An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Aug;48(8):2748-2757. doi: 10.1007/s10803-018-3536-7.

  PMID: 29536216 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Impulsive Behavior; Psychotic Disorders; Aggression

Interventions

Tobacco Use Cessation Devices

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Behavior; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Social Behavior

Intervention Hierarchy (Ancestors)

Therapeutics

Limitations and Caveats

Recruitment for this study did not reach its original intended size due to difficulties from the Covid19 pandemic.

Results Point of Contact

• Title: Alan S. Lewis, M.D., Ph.D.
• Organization: Vanderbilt University Medical Center

alan.s.lewis@vumc.org

615-875-4027

Study Officials

• Alan S Lewis, MD, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry and Behavioral Sciences

Study Record Dates

• First Submitted: February 7, 2019
• First Posted: February 12, 2019
• Study Start: May 10, 2019
• Primary Completion: February 24, 2020
• Study Completion: February 24, 2020
• Last Updated: April 29, 2022
• Results First Posted: April 29, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)