Clinical trial NCT02131129: rTMS in First Episode Psychosis
Official title: Cortical Activation and Cognitive Performance During Repetitive Transcranial Magnetic Stimulation in First-Episode Psychosis: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Schizophreniform Disorder
Schizoaffective Disorder
Keywords: schizophrenia
schizophreniform disorder
schizoaffective disorder
first episode
psychosis
cognition
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Neuronetics
First posted: 2014-05-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study proposes to examine the application of rTMS for the treatment of cognitive dysfunction in FEP. This is an important population for study because if effective, rTMS may represent a preventative treatment for the development of social and vocational impairment that is associated with cognitive dysfunction in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-cognitive effects of rTMS through the use of functional magnetic resonance imaging (fMRI) at baseline and following the course of rTMS administration.

Detailed description: Schizophrenia is a chronic and disabling illness that typically begins in the late teen and early adult years.1 This illness is associated with significant impairments in areas such as independent living, social functioning, and vocational functioning.2 Indeed, only 10% of people with schizophrenia are employed, translating into annual lost wages of nearly 15 billion dollars.3,4 Schizophrenia also represents an important societal burden as this illness has been estimated to cost over 40 billion dollars each year in the United States alone.5

Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment for neuropsychiatric illness. A non-invasive intervention, rTMS utilizes the application of a repetitively pulsed magnetic field over the scalp to induce an electric field within a discrete area of the cerebral cortex. This electric field results in altered ion flow across the neuronal cellular membrane and ultimately changes in neuronal polarization. The end result is altered neuronal activity in the area of the cerebral cortex where the rTMS is applied.12 rTMS is a safe and well-tolerated intervention that received FDA approval for treatment refractory major depressive disorder in 2008 and has since become commonly used in clinical practice.13

This study proposes to examine the application of rTMS for the treatment of cognitive dysfunction in FEP. This is an important population for study because if effective, rTMS may represent a preventative treatment for the development of social and vocational impairment that is associated with cognitive dysfunction in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-cognitive effects of rTMS through the use of functional magnetic resonance imaging (fMRI) at baseline and following the course of rTMS administration.

Eligibility criteria: Inclusion Criteria:

* 18-40 years of age at study entry
* Male or female
* DSM IV-TR Diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder as confirmed by Structured Clinical Interview for DSM-IV-TR (SCID)44
* Subjects in their first-episode of psychosis, defined as the onset of clinically significant psychotic symptoms within the past five years as determined by first medical record documentation of these conditions
* BACS composite t-score of 40 or less at baseline assessment
* Clinical stability as defined by:

  * CGI-S score of less than or equal to 4 (moderately ill) at randomization AND
  * Subjects must not have experienced an exacerbation of their illness within 4 weeks prior to randomization, leading to an intensification of psychiatric care in the opinion of the investigator. Examples of intensification of care include, but are not limited to: inpatient hospitalization, day/partial hospitalization, outpatient crisis management, or psychiatric treatment in an emergency room AND
  * Antipsychotic treatment stability for at least 4 weeks prior to randomization (no change in antipsychotic dosing or addition of any new antipsychotic medication).
* Able to give informed consent
* Subjects must be willing and able to adhere to study schedule
* Outpatient or Inpatient treatment status
* Female subjects of childbearing potential must test negative for pregnancy at screening and baseline visit

Exclusion Criteria:

* Life-time history of a seizure, excluding febrile seizures and those induced by substance withdrawal
* Metallic objects planted in or near the head, including implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, ventriculoperitoneal shunt, or cochlear implants
* First degree relative (that is, biological father, mother, brother, sister, or child) with idiopathic epilepsy or other seizure disorder
* History of significant neurological illness (including stroke, CNS infection with persistent neurologic deficit, or other event deemed significant by PI)
* History of head trauma as defined by a loss of consciousness or a post-concussive syndrome deemed significant by PI
* Pregnancy or breast feeding
* Known IQ \< 70 based on medical history
* Current DSM-IV-TR diagnosis of alcohol or drug dependence (excluding nicotine or caffeine)
* Subjects with current acute, serious, or unstable medical conditions, including, but not limited to: inadequately controlled diabetes, asthma, COPD, severe hypertriglyceridemia, recent cerebrovascular accidents, acute systemic infection or immunologic disease, unstable cardiovascular disorders, malnutrition, or hepatic, renal gastroenterological, respiratory, endocrine, neurologic, hematologic, or infectious diseases based on medical history or physical examination.
* Subjects with contraindications to MRI or otherwise unable to tolerate MRI procedure
* Subjects considered a high risk for suicidal acts - active suicidal ideation as determined by clinical interview OR any suicide attempt in 90 days prior to screening
* Subjects who have participated in a clinical trial with any pharmacological treatment intervention for which they received study-related medication in the 4 weeks prior to randomization
* Subjects who require concomitant treatment with prohibited medication, as specified in Attachment 2
* Subjects with a history of electroconvulsive therapy

Primary outcomes:
measure: Cognitive Performance
timeFrame: For within-group comparisons, scores at V13 (day 15) and V14 (follow-up two weeks after V13) were compared to baseline
measure: Cortical Activation
timeFrame: Change from Baseline (day 1) to Visit 13 (day 15)
Secondary outcomes:
measure: Cognitive Performance
timeFrame: 14 days
measure: Cognitive Performance
timeFrame: 14 days
measure: Symptoms
timeFrame: For within-group comparisons, scores at V13 (day 15) and V14 (follow-up two weeks after V13) were compared to baseline
measure: Negative Symptoms
timeFrame: Assessed at Baseline (day 0), Midpoint (day 8), and Endpoint (day 15)
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: IU Center for NeuroImaging
state: Indiana
city: Indianapolis
country: United States
facility: Prevention and Recovery Center for Early Psychosis
state: Indiana
Study officials:
References: