Boost rTMS for Auditory Verbal Hallucinations

NCT ID: NCT03544333

Last Updated: 2021-05-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-16
• Study Completion Date: 2019-01-22

Brief Summary

This is a randomized, placebo controlled, double-blind clinical trial. The investigators aim to examine the safety and efficacy of repeated transcranial magnetic stimulation (rTMS) for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia who are not taking antipsychotic medication. The investigators employ a novel, accelerated protocol with only four sessions of low-frequency rTMS in one day. The effects of this accelerated protocol will be compared to the sham stimulation. Additionally, the investigators will examine the effects of rTMS on a neurophysiological level by evaluating mechanism of action in the temporo-parietal lobe by means of functional magnetic resonance imaging.

Detailed Description

Auditory verbal hallucinations affect up to 70% of schizophrenia patients (Waters, 2012), yet, even extended antipsychotic medication does not ameliorate AVH in 20-30% of patients (Sukhwinder S Shergill et al., 2007) and is often accompanied by side effects (Leucht et al., 2009). Therefore, it is crucial to develop and assess promising potentially beneficial therapeutic options.

Non-invasive brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS) have been proposed to disrupt mechanisms in question. A number of meta-analyses (Aleman, Sommer, & Kahn, 2007; Demeulemeester et al., 2012; Freitas, Fregni, & Pascual-Leone, 2009; C. W. Slotema, Blom, van Lutterveld, Hoek, & Sommer, 2014; C. W. Slotema, Dirk Blom, Hoek, & Sommer, 2010; Tranulis, Sepehry, Galinowski, & Stip, 2008) found significant effect sizes ranging from 0.42 to 1.04 for 1Hz rTMS over the left temporo-parietal junction for the treatment of AVH. However, the majority of studies so far investigated the effects of rTMS in treatment resistant schizophrenia patients as an ad-on or second-line treatment.

No study to date has explored the effects of rTMS either as a first-line treatment or in the initial stage of the illness. This is surprising, considering the fact that rTMS is a safe treatment with minimal side-effects (Rossi, Hallett, Rossini, & Pascual-Leone, 2009) that could be used already in the earlier phase of treatment. This stands in considerable contrast to the range of side-effects associated with antipsychotics (Leucht et al., 2017) that can be disabling for patients and lead to lower quality of life.

Therefore, the crucial next step is (1) to explore the effects of rTMS in medication-free patients from the whole schizophrenia spectrum and (2) to use an accelerated protocol of multiple rTMS-sessions within a short period of time. To make this assessment feasible, considering that patients have to be off medication, the safest and also most efficient way is an accelerated rTMS protocol. The great advantage of such an approach is that the effects of rTMS can be investigated independently of potentially influencing effects of antipsychotics and at the same time assess the efficacy of rTMS within a very short amount of time.

In the proposed study, the investigators aim to determine the efficacy of rTMS as a potential treatment for AVH in schizophrenia and thus reduce suffering in patients and their relatives.

Conditions

Schizophrenia; Auditory Hallucination

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

real transcranial magnetic stimulation

In the treatment arm, patients will receive 1Hz of repetitive transcranial magnetic stimulation (rTMS) over the left Sylvian parietal temporal area (area Spt) four times on 1 day (1 pulse/second and a total of 1'000 pulses: 16 minutes' protocol at 100 % of motor threshold modified based on Hoffman et al.,1999). Area Spt will be localized via baseline structural imaging and our Localite TMS navigation system.

Group Type: EXPERIMENTAL

transcranial magnetic stimulation

Intervention Type: DEVICE

We will assess safety and efficacy of the following protocol: 1Hz of rTMS over the Sylvian parietal temporal area (area Spt) four times on 1 day (1 pulse/second and a total of 1'000 pulses: 16 minutes' protocol at 100 % of motor threshold modified based on Hoffman et al., 1999). Area Spt will be localized via baseline structural imaging and our Localite TMS navigation system.

sham transcranial magnetic stimulation

In the comparator arm, patients will receive no stimulation. The TMS coil adjusted to the patients head will not be plugged into the TMS machine and can thus not have an effect on the brain. Yet, patients will hear the same noises from a coil that is plugged in, see the TMS machine running, and area Spt localized via baseline structural imaging and our Localite TMS navigation system.

Group Type: PLACEBO_COMPARATOR

transcranial magnetic stimulation

Intervention Type: DEVICE

We will assess safety and efficacy of the following protocol: 1Hz of rTMS over the Sylvian parietal temporal area (area Spt) four times on 1 day (1 pulse/second and a total of 1'000 pulses: 16 minutes' protocol at 100 % of motor threshold modified based on Hoffman et al., 1999). Area Spt will be localized via baseline structural imaging and our Localite TMS navigation system.

Interventions

transcranial magnetic stimulation

We will assess safety and efficacy of the following protocol: 1Hz of rTMS over the Sylvian parietal temporal area (area Spt) four times on 1 day (1 pulse/second and a total of 1'000 pulses: 16 minutes' protocol at 100 % of motor threshold modified based on Hoffman et al., 1999). Area Spt will be localized via baseline structural imaging and our Localite TMS navigation system.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Male or female, aged 18 to 65

4. Diagnosed with Diagnostic and Statistical Manual (DSM) V diagnosis of schizophrenia (295.90), schizoaffective disorder (295.70), or brief psychotic disorder (298.80), prone to AVH in the acute phases of the disorder

5. Willing to adhere to the rTMS regimen

6. No antipsychotic medication in the last two weeks prior to the start of the study as well as no antipsychotic medication during participation in the study

7. Agreement to adhere to Lifestyle Considerations throughout study duration

Exclusion Criteria

1. Current use of antipsychotic medication within the last 2 weeks

2. Electroconvulsive therapy or rTMS within three months (see the TMS screening questionnaire)

3. History of seizures

4. Presence of implanted electronic device or metal implant in the head and neck region (DBS, cochlear implant, etc.)

5. Pregnancy, as assessed with a pregnancy test prior to every MRI measurement, or lactation

6. Any active general medical condition or central nervous system disease which can affect cognition or response to treatment

7. Treatment with another investigational drug or other intervention within 2 weeks

8. Current diagnosis of delirium, dementia, or amnestic amnesiac disorder; Diagnosis of mental retardation; Current (within the past three months) diagnosis of active substance dependence, or active substance abuse within the past week as indicated by self-report.

9. Patients who are cognitively impaired and are thus not able to give informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwell Health

OTHER

Sponsor Role: lead

Responsible Party

Philipp Homan

Assistant Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Philipp Homan, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Zucker Hillside Hospital, New York City, USA.

Locations

The Zucker Hillside Hospital, Northwell Health

Manhasset, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

18-0024

Identifier Type: -

Identifier Source: org_study_id