Using Transcranial Magnetic Stimulation (TMS) to Understand 'Negative' Symptoms of Schizophrenia

NCT03648268 | Completed DMC FDA Device

• 1 other identifier: 2018P000321
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to learn how transcranial magnetic stimulation (TMS) helps improve negative symptoms of schizophrenia. These 'negative symptoms' include anhedonia (the inability to enjoy things), low motivation, and decreased facial expression. TMS is a noninvasive way of stimulating the brain. TMS uses a magnetic field to cause changes in activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study we will be stimulating the brain to learn more about how TMS may improve these symptoms from schizophrenia.

Conditions

Schizophrenia; Negative Type; Schizophrenic; Schizo Affective Disorder

Keywords

brain; networks; schizophrenia

Outcome Measures

Primary Outcomes (1)

• Change in Negative Symptom Severity

  We will evaluate the effect of sham vs active rTMS on negative symptom severity in the group with Cerebellar targeted rTMS and in the group with DLPFC targeted rTMS

  Before treatment (Baseline) and 1 week post treatment

Secondary Outcomes (2)

• Change in Cerebellar - Prefrontal Functional Connectivity

  Before treatment (Baseline) and 1 week post treatment

• Change in Auditory Hallucination Severity

  Before treatment (Baseline) and 1 week post treatment

Study Arms (4)

Active DLPFC rTMS

ACTIVE COMPARATOR

Active repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the right DLPFC at 80% of active motor threshold.

Device: repetitive Transcranial Magnetic Stimulation (rTMS)

Sham DLPFC rTMS

SHAM COMPARATOR

Sham repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the right DLPFC

Device: repetitive Transcranial Magnetic Stimulation (rTMS)

Active cerebellum rTMS

ACTIVE COMPARATOR

Active repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum at 100% of active motor threshold.

Device: repetitive Transcranial Magnetic Stimulation (rTMS)

Sham cerebellum rTMS

SHAM COMPARATOR

Sham repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum

Device: repetitive Transcranial Magnetic Stimulation (rTMS)

Interventions

repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity. The pattern of rTMS will consist of either: intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses. OR sham stimulation

Also known as: iTBS

Active DLPFC rTMS; Active cerebellum rTMS; Sham DLPFC rTMS; Sham cerebellum rTMS

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18-55 years
• At pre-visit screening (see attached phone screening questionnaire): participants must report that they have been given a diagnosis of schizophrenia or schizoaffective disorder by a mental health professional
• Must be able to read, speak, and understand English
• Must be judged by study staff to be capable of completing the study procedures
• Diagnosis of schizophrenia or schizoaffective disorder according to DSM-V criteria and confirmed by SCID
• Participants will be in stable outpatient treatment with no recent (within the past 30 days) hospitalizations or changes in their mediation regimens

You may not qualify if:

• DSM-V intellectual disability
• substance use disorder within the past three months
• Ambidexterity (the EEfRT task assumes participants are not ambidextrous)
• Any history of progressive or genetic neurological disorder (e.g. Parkinson's disease, multiple sclerosis, tubular sclerosis, Alzheimer's Disease) or acquired neurological disease (e.g. stroke, traumatic brain injury, tumor), including intracranial lesions
• History of head trauma resulting in any loss of consciousness (\>15 minutes) or neurological sequelae
• Current history of poorly controlled headaches including chronic medication for migraine prevention
• History of fainting spells of unknown or undetermined etiology that might constitute seizures
• History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist
• Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
• Any metal in the brain or skull (excluding dental fillings) or elsewhere in the body unless cleared by the responsible covering MD (e.g. MRI compatible joint replacement)
• Any devices such as pacemaker, medication pump, nerve stimulator, TENS unit, ventriculo-peritoneal shunt unless cleared by the responsible covering MD
• All female participants of child bearing age will be required to have a pregnancy test; any participant who is pregnant will not be enrolled in the study
• Any changes in medications or hospitalizations within the past 30 days.
• Subjects who, in the investigator's opinion, might not be suitable for the study or would be unable to tolerate the study visit

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Mclean Hospital: collaborator
• Harvard University: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Related Publications (16)

• Rabinowitz J, Levine SZ, Garibaldi G, Bugarski-Kirola D, Berardo CG, Kapur S. Negative symptoms have greater impact on functioning than positive symptoms in schizophrenia: analysis of CATIE data. Schizophr Res. 2012 May;137(1-3):147-50. doi: 10.1016/j.schres.2012.01.015. Epub 2012 Feb 6.

  PMID: 22316568 BACKGROUND

• Robertson BR, Prestia D, Twamley EW, Patterson TL, Bowie CR, Harvey PD. Social competence versus negative symptoms as predictors of real world social functioning in schizophrenia. Schizophr Res. 2014 Dec;160(1-3):136-41. doi: 10.1016/j.schres.2014.10.037. Epub 2014 Nov 7.

  PMID: 25468184 BACKGROUND

• Roth BJ, Cohen LG, Hallett M. The electric field induced during magnetic stimulation. Electroencephalogr Clin Neurophysiol Suppl. 1991;43:268-78.

  PMID: 1773764 BACKGROUND

• Roth BJ, Saypol JM, Hallett M, Cohen LG. A theoretical calculation of the electric field induced in the cortex during magnetic stimulation. Electroencephalogr Clin Neurophysiol. 1991 Feb;81(1):47-56. doi: 10.1016/0168-5597(91)90103-5.

  PMID: 1705219 BACKGROUND

• Walsh V, Cowey A. Transcranial magnetic stimulation and cognitive neuroscience. Nat Rev Neurosci. 2000 Oct;1(1):73-9. doi: 10.1038/35036239.

  PMID: 11252771 BACKGROUND

• Eldaief MC, Halko MA, Buckner RL, Pascual-Leone A. Transcranial magnetic stimulation modulates the brain's intrinsic activity in a frequency-dependent manner. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21229-34. doi: 10.1073/pnas.1113103109. Epub 2011 Dec 12.

  PMID: 22160708 BACKGROUND

• Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, Roffman JL, Smoller JW, Zollei L, Polimeni JR, Fischl B, Liu H, Buckner RL. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol. 2011 Sep;106(3):1125-65. doi: 10.1152/jn.00338.2011. Epub 2011 Jun 8.

  PMID: 21653723 BACKGROUND

• Power JD, Cohen AL, Nelson SM, Wig GS, Barnes KA, Church JA, Vogel AC, Laumann TO, Miezin FM, Schlaggar BL, Petersen SE. Functional network organization of the human brain. Neuron. 2011 Nov 17;72(4):665-78. doi: 10.1016/j.neuron.2011.09.006.

  PMID: 22099467 BACKGROUND

• Demirtas-Tatlidede A, Freitas C, Cromer JR, Safar L, Ongur D, Stone WS, Seidman LJ, Schmahmann JD, Pascual-Leone A. Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia. Schizophr Res. 2010 Dec;124(1-3):91-100. doi: 10.1016/j.schres.2010.08.015.

  PMID: 20817483 BACKGROUND

• Garg S, Sinha VK, Tikka SK, Mishra P, Goyal N. The efficacy of cerebellar vermal deep high frequency (theta range) repetitive transcranial magnetic stimulation (rTMS) in schizophrenia: A randomized rater blind-sham controlled study. Psychiatry Res. 2016 Sep 30;243:413-20. doi: 10.1016/j.psychres.2016.07.023. Epub 2016 Jul 16.

  PMID: 27450744 BACKGROUND

• Schmahmann JD. An emerging concept. The cerebellar contribution to higher function. Arch Neurol. 1991 Nov;48(11):1178-87. doi: 10.1001/archneur.1991.00530230086029.

  PMID: 1953406 BACKGROUND

• Schmahmann JD. Dysmetria of thought: clinical consequences of cerebellar dysfunction on cognition and affect. Trends Cogn Sci. 1998 Sep 1;2(9):362-71. doi: 10.1016/s1364-6613(98)01218-2.

  PMID: 21227233 BACKGROUND

• Andreasen NC, Paradiso S, O'Leary DS. "Cognitive dysmetria" as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophr Bull. 1998;24(2):203-18. doi: 10.1093/oxfordjournals.schbul.a033321.

  PMID: 9613621 BACKGROUND

• Parker KL, Narayanan NS, Andreasen NC. The therapeutic potential of the cerebellum in schizophrenia. Front Syst Neurosci. 2014 Sep 15;8:163. doi: 10.3389/fnsys.2014.00163. eCollection 2014.

  PMID: 25309350 BACKGROUND

• Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.

  PMID: 15664172 BACKGROUND

• Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.

  PMID: 19833552 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Roscoe Brady, MD, PhD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The subjects, care providers, investigators and outcome assessors will all be blinded as to the randomization sequence, and thus will be blinded as to sham vs active TMS status. Blinding codes are used to determine which side of an active/passive Magpro coil (cool B65 A/P, Magventure A/S, Denmark) is used for stimulation.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Model Details: There will be four groups: an active DLPFC TMS group, an active TMS cerebellum group, a sham DLPFC group, and a sham cerebellum group. Participants will be randomized to one of these group groups, and they will receive that type of stimulation for the entire study.

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: August 27, 2018
• Study Start: May 2, 2019
• Primary Completion: December 22, 2023
• Study Completion: December 22, 2023
• Last Updated: March 27, 2024

Record last verified: 2024-03

Locations

US (1)