NCT00308997

Brief Summary

This study will determine the efficacy of MRI-guided transcranial magnetic stimulation (TMS)in reducing "voices" and other symptoms experienced by people with schizophrenia and schizoaffective disorder. In addition, the study will determine duration of improvement obtained during the course of trial participation via on-going monthly contact with study participants for up to 1 year after the trial.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
85

participants targeted

Target at P25-P50 for phase_2 schizophrenia

Timeline
Completed

Started Feb 2006

Longer than P75 for phase_2 schizophrenia

Geographic Reach
1 country

1 active site

Status
completed

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2006

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 28, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 30, 2006

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2011

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2012

Completed
10 months until next milestone

Results Posted

Study results publicly available

January 24, 2013

Completed
Last Updated

April 2, 2020

Status Verified

March 1, 2020

Enrollment Period

5.6 years

First QC Date

March 28, 2006

Results QC Date

November 14, 2012

Last Update Submit

March 31, 2020

Conditions

SchizophreniaHallucinations

Keywords

Auditory HallucinationsSchizophreniaSchizoaffective DisorderRepetitive Transcranial Magnetic StimulationWernicke's AreaSuperior Temporal Gyrus

Outcome Measures

Primary Outcomes (3)

  • Hallucination Change Score - Right (HCS-right)

    HCS score for participants assessed after 5 sessions, 16 minutes per session, who received either rTMS or sham stimulation delivered to the right superior temporal gyrus. HCS was anchored at 0 (corresponding to no AVHs), 10 (no change in hallucination severity) and 20 (AVHs twice as severe as baseline). Lower scores correspond to greater improvement

    After 5 sessions of rTMS

  • Hallucination Change Score - Left (HCS-left)

    HCS score for participants assessed after 5 sessions, 16 minutes per session, who received either rTMS or sham stimulation delivered to the left superior temporal gyrus. HCS was anchored at 0 (corresponding to no AVHs), 10 (no change in hallucination severity) and 20 (AVHs twice as severe as baseline). Lower scores correspond to greater improvement

    After 5 sessions of rTMS

  • Hallucination Change Score (HCS)

    HCS score assessed after 15 sessions, 16 minutes per session, delivered to both right superior temporal and left superior temporal gyrus sites using either rTMS or sham stimulation. For patients dropping out of the trial prematurely, last-observation-carried-forward data were used for this outcome variable. HCS was anchored at 0 (corresponding to no AVHs), 10 (no change in hallucination severity) and 20 (AVHs twice as severe as baseline). Lower scores correspond to greater improvement

    After 15 sessions of rTMS

Secondary Outcomes (3)

  • Change in Hallucination Frequency

    After 15 sessions of rTMS

  • Change in Total Auditory Hall Rating Scale (AHRS) Score

    After 15 sessions of rTMS

  • Clinical Global Improvement (CGI)Improvement

    After 15 sessions of rTMS

Study Arms (2)

1

EXPERIMENTAL

Active 1-hertz Repetitive Transcranial Magnetic Stimulation to Wernicke's area and right homologous area

Device: Active 1-Hertz Repetitive transcranial magnetic stimulation

2

SHAM COMPARATOR

sham rTMS to Wernicke's area and a right homologous area

Device: 1-hertz Repetitive Transcranial Magnetic Stimulation

Interventions

1-hertz Repetitive Transcranial Magnetic StimulationDEVICE

Sham stimulation given to Wernicke's area or a right homologous area for 16 minutes per day x 5 days for week I, the same for week II with switch from right to left or left to right, and 5 more stimulation sessions (16 minutes per session) to the side producing greater benefit for week III.

Also known as: Magstim Rapid-2
2
Active 1-Hertz Repetitive transcranial magnetic stimulationDEVICE

Active stimulation given to Wernicke's area or a right homologous area for 16 minutes per day x 5 days for week I, the same for week II with switch from right to left or left to right, and 5 more stimulation sessions (16 minutes per session) to the side producing greater benefit for week III.

Also known as: Magstim Rapid-2
1

Eligibility Criteria

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

You may qualify if:

  • Auditory hallucinations that occur at least five times per day, on average
  • Diagnosis of schizophrenia or schizoaffective disorder

You may not qualify if:

  • Pregnant
  • History of seizure that is not drug-induced or secondary to alcohol withdrawal
  • Changes in antipsychotic drug dosages within 4 weeks of study entry (patients do not need to be on antipsychotic medication to be included)
  • Current significant untreated or unstable medical illness (e.g., poorly controlled diabetes mellitus, severe hypertension, unstable cardiac arrhythmia)
  • Inability to understand the nature of the study due to severe psychotic disorganization, mental retardation, etc.
  • Significant neurological condition (e.g., traumatic brain injury, multiple sclerosis)
  • Factors that would preclude an MRI scan (e.g., severe obesity, claustrophobia, certain surgical implants with metallic components, metal shavings in the eye acquired while working as machinist)
  • Cardiac pacemaker

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Yale Psychiatric Research

New Haven, Connecticut, 06519, United States

Location

Related Publications (8)

  • Hoffman RE, Gueorguieva R, Hawkins KA, Varanko M, Boutros NN, Wu YT, Carroll K, Krystal JH. Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample. Biol Psychiatry. 2005 Jul 15;58(2):97-104. doi: 10.1016/j.biopsych.2005.03.041.

    PMID: 15936729BACKGROUND

  • Hoffman RE, Boutros NN, Hu S, Berman RM, Krystal JH, Charney DS. Transcranial magnetic stimulation and auditory hallucinations in schizophrenia. Lancet. 2000 Mar 25;355(9209):1073-5. doi: 10.1016/S0140-6736(00)02043-2.

    PMID: 10744097BACKGROUND

  • Hoffman RE, Cavus I. Slow transcranial magnetic stimulation, long-term depotentiation, and brain hyperexcitability disorders. Am J Psychiatry. 2002 Jul;159(7):1093-102. doi: 10.1176/appi.ajp.159.7.1093.

    PMID: 12091184BACKGROUND

  • Poulet E, Brunelin J, Bediou B, Bation R, Forgeard L, Dalery J, d'Amato T, Saoud M. Slow transcranial magnetic stimulation can rapidly reduce resistant auditory hallucinations in schizophrenia. Biol Psychiatry. 2005 Jan 15;57(2):188-91. doi: 10.1016/j.biopsych.2004.10.007.

    PMID: 15652879BACKGROUND

  • Chibbaro G, Daniele M, Alagona G, Di Pasquale C, Cannavo M, Rapisarda V, Bella R, Pennisi G. Repetitive transcranial magnetic stimulation in schizophrenic patients reporting auditory hallucinations. Neurosci Lett. 2005 Jul 22-29;383(1-2):54-7. doi: 10.1016/j.neulet.2005.03.052. Epub 2005 Apr 15.

    PMID: 15936511BACKGROUND

  • Fitzgerald PB, Benitez J, Daskalakis JZ, Brown TL, Marston NA, de Castella A, Kulkarni J. A double-blind sham-controlled trial of repetitive transcranial magnetic stimulation in the treatment of refractory auditory hallucinations. J Clin Psychopharmacol. 2005 Aug;25(4):358-62. doi: 10.1097/01.jcp.0000168487.22140.7f.

    PMID: 16012279BACKGROUND

  • Hoffman RE, Hampson M, Wu K, Anderson AW, Gore JC, Buchanan RJ, Constable RT, Hawkins KA, Sahay N, Krystal JH. Probing the pathophysiology of auditory/verbal hallucinations by combining functional magnetic resonance imaging and transcranial magnetic stimulation. Cereb Cortex. 2007 Nov;17(11):2733-43. doi: 10.1093/cercor/bhl183. Epub 2007 Feb 13.

    PMID: 17298962BACKGROUND

  • Hoffman RE, Wu K, Pittman B, Cahill JD, Hawkins KA, Fernandez T, Hannestad J. Transcranial magnetic stimulation of Wernicke's and Right homologous sites to curtail "voices": a randomized trial. Biol Psychiatry. 2013 May 15;73(10):1008-14. doi: 10.1016/j.biopsych.2013.01.016. Epub 2013 Feb 26.

    PMID: 23485015DERIVED

Related Links

MeSH Terms

Conditions

SchizophreniaHallucinationsPsychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental DisordersPerceptual DisordersNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Ralph Hoffman, MD
Organization
Yale University School of Medicine
Ralph.Hoffman@yale.edu
203-688-9734

Study Officials

  • Ralph E. Hoffman, MD

    Yale University School of Medicine, Department of Psychiatry

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 28, 2006

First Posted

March 30, 2006

Study Start

February 1, 2006

Primary Completion

September 1, 2011

Study Completion

April 1, 2012

Last Updated

April 2, 2020

Results First Posted

January 24, 2013

Record last verified: 2020-03

Locations

US(1)