NCT03497299

Brief Summary

Tobacco smokers with schizophrenia are known to be resistant smokers, with high rates of smoking and inability to quit in the long-term, often related to smoking relapse. This may relate to problems with frontal lobe function associated with schizophrenia, which make these patients have great difficulty in dealing with smoking withdrawal, urges and cravings. The current study will develop a combination approach that takes advantage of brain stimulation of the frontal lobes (repetitive transcranial magnetic stimulation (rTMS), in combination with the anti-smoking drug varenicline, to prevent smoking lapse using a well-established human laboratory method. Results from this study may have important implications for developing novel treatment approaches for smokers with schizophrenia.

Trial Health

15
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jul 2018

Typical duration for phase_2

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 29, 2018

Completed
15 days until next milestone

First Posted

Study publicly available on registry

April 13, 2018

Completed
3 months until next milestone

Study Start

First participant enrolled

July 1, 2018

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2022

Completed
Last Updated

September 6, 2023

Status Verified

September 1, 2023

Enrollment Period

4.2 years

First QC Date

March 29, 2018

Last Update Submit

September 1, 2023

Conditions

Tobacco Use DisorderSchizophreniaCognitive FunctioningCraving

Keywords

SchizophreniaSmokingLapseVareniclineSham Repetitive Transcranial Magnetic Stimulation (rTMS)

Outcome Measures

Primary Outcomes (1)

  • Time to Smoking Lapse (TTL)

    A measure of ability to resist smoking lapse during a 50 minute ad lib cigarette smoking period at Day 28 of the trial in SWS. Higher values indicate increased ability to resist smoking lapse.

    Day 28

Secondary Outcomes (2)

  • Smoking Topography

    Day 28 (in comparison to baseline results at Day 0)

  • Spatial Delayed Response (SDR)/Visuospatial Working Memory (VSWM) Task

    Day 28 (in comparison to baseline results at Day 0)

Study Arms (2)

Active rTMS (20Hz)

EXPERIMENTAL

Active rTMS administered with the MagProX100/R30 stimulator equipped with the B65 active coil for dorsolateral prefrontal cortex (DLPFC) stimulator (MagVenture, Farum, Denmark).The randomization order will be determined by a project scientist from Temerty. While the primary aim of this study is not to treat individuals with tobacco dependence, it is imperative that participants attend weekly study visits in an attempt to achieve end of study (Day 28) tobacco abstinence.

Device: Active rTMS (20Hz)

Sham rTMS

SHAM COMPARATOR

Sham rTMS administered with the MagProX100/R30 stimulator equipped with the B65 placebo coil for DLPFC stimulator (MagVenture, Farum, Denmark). The randomization order will be determined by a project scientist from Temerty. While the primary aim of this study is not to treat individuals with tobacco dependence, it is imperative that participants attend weekly study visits in an attempt to achieve end of study (Day 28) tobacco abstinence.

Device: Sham rTMS

Interventions

Active rTMS (20Hz)DEVICE

Repetitive Transcranial Magnetic Stimulation (rTMS) Procedures: On Day 1, participants will be randomly assigned to receive active or sham rTMS using the MagProX100/R30 stimulator equipped with the B65 active/ placebo coil for DLPFC stimulator (MagVenture, Farum, Denmark) for a period of 28 days.

Active rTMS (20Hz)
Sham rTMSDEVICE

Repetitive Transcranial Magnetic Stimulation (rTMS) Procedures: On Day 1, participants will be randomly assigned to receive active or sham rTMS using the MagProX100/R30 stimulator equipped with the B65 active/ placebo coil for DLPFC stimulator (MagVenture, Farum, Denmark) for a period of 28 days.

Sham rTMS

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • smokers with schizophrenia, non-treatment seeking (i.e., not trying to quit as indicated by \<7 on the contemplation ladder)
  • ages 18-55
  • IQ ≥80 on the Weschler Test of Adult Reading
  • Fagerstrom Test for Nicotine Dependence (FTND) ≥5
  • smoke ≥ 10 cigarettes per day
  • must meet SCID for DSM-5 diagnosis criteria for schizophrenia
  • must be in stable remission from positive symptoms of psychosis as judged by a PANSS positive score total score \<70
  • must be receiving a stable dose of antipsychotics for \>1month.

You may not qualify if:

  • substance use (except nicotine or caffeine) in the last month
  • a history of alcohol/drug abuse in the 3 months before study enrolment and use of opioids (e.g., meperidine, oxycodone, methadone)
  • current use of smoking cessation aids (e.g., nicotine replacement therapy, bupropion or varenicline)
  • pregnancy or nursing
  • a history of renal insufficiency or a hypersensitivity to varenicline (Chantix®)
  • a history of neurological illness like epilepsy or medical condition known to significantly influence neurocognitive function, at the discretion of the PI
  • any other medical condition deemed relevant by the PI

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (2)

  • Kozak K, Sharif-Razi M, Morozova M, Gaudette EV, Barr MS, Daskalakis ZJ, Blumberger DM, George TP. Effects of short-term, high-frequency repetitive transcranial magnetic stimulation to bilateral dorsolateral prefrontal cortex on smoking behavior and cognition in patients with schizophrenia and non-psychiatric controls. Schizophr Res. 2018 Jul;197:441-443. doi: 10.1016/j.schres.2018.02.015. Epub 2018 Feb 24.

    PMID: 29486960RESULT

  • Wing VC, Bacher I, Wu BS, Daskalakis ZJ, George TP. High frequency repetitive transcranial magnetic stimulation reduces tobacco craving in schizophrenia. Schizophr Res. 2012 Aug;139(1-3):264-6. doi: 10.1016/j.schres.2012.03.006. Epub 2012 Mar 29. No abstract available.

    PMID: 22464727RESULT

MeSH Terms

Conditions

Tobacco Use DisorderSchizophreniaSmoking

Condition Hierarchy (Ancestors)

Substance-Related DisordersChemically-Induced DisordersMental DisordersSchizophrenia Spectrum and Other Psychotic DisordersBehavior
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
The investigators will have a sham rTMS coil to provide full blinding for the active rTMS condition.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: The study is a randomized controlled trial of active versus sham high frequency rTMS to the dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia who have co-occurring tobacco use disorder. The duration of treatment is 4 weeks and all subjects would receive open label Varenicline 2mg/day. The primary outcome measure is time to lapse to smoking.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief, Addictions Division

Study Record Dates

First Submitted

March 29, 2018

First Posted

April 13, 2018

Study Start

July 1, 2018

Primary Completion

August 31, 2022

Study Completion

August 31, 2022

Last Updated

September 6, 2023

Record last verified: 2023-09

Data Sharing

IPD Sharing
Will not share