iTBS for Psychosis

(iSCIP Trial)

Overseen By Andrea Joanlanne

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Northwell Health

Must be taking: Antipsychotics

Must not be taking: Benzodiazepines

Disqualifiers: Substance use disorder, Type 1 diabetes, Unstable medical illness, Neurological disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 22

Duration: 4 weeks

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to have been on a stable dose of antipsychotic medication for at least 30 days before joining, so you will not need to stop taking your current antipsychotic medications. However, if you are taking a benzodiazepine at a dose equivalent to lorazepam 2 mg/day or higher, you may need to adjust or stop it.

What data supports the effectiveness of the treatment iTBS for psychosis?

Research shows that iTBS can reduce negative symptoms in schizophrenia and improve depression in bipolar disorder, suggesting it might help with psychosis too. In a study, iTBS significantly decreased negative symptoms in schizophrenia patients, and another study found high response rates in bipolar depression, indicating its potential effectiveness. ^{1 2 3 4 5}

Is iTBS safe for humans?

Research shows that iTBS (Intermittent Theta Burst Stimulation) is generally safe and well-tolerated in humans, with studies reporting no adverse events in patients with bipolar depression and treatment-resistant depression. ^{5 6 7 8 9}

How is iTBS treatment different from other treatments for psychosis?

iTBS (intermittent theta burst stimulation) is a unique noninvasive brain stimulation treatment that can be delivered in just a few minutes, unlike traditional methods that take much longer. It directly stimulates specific brain areas, potentially enhancing cognitive and functional recovery, and is being explored for its rapid and safe effects in various mental health conditions. ^{5 7 9 10 11}

What is the purpose of this trial?

The goal of this clinical trial is to examine if iTBS applied to the DMPFC improves social cognitive performance compared to sham stimulation in people diagnosed with schizophrenia, schizoaffective disorder, schizophreniform disorder, or psychotic disorder not otherwise specified. The main objectives of this trial are: * Compare changes in social cognitive performance between the active vs. sham treatment groups * Compare changes in social cognitive network functional connectivity between the active vs. sham treatment groups Each participant will receive iTBS (active or sham) five days per week for four consecutive weeks. Functional magnetic resonance imaging (fMRI) scans, clinical assessments, and cognitive tests will be performed at pre-treatment, post-treatment, and 6 months after the completion of treatment.

Eligibility Criteria

This trial is for individuals aged 18-39 with schizophrenia, schizoaffective disorder, schizophreniform disorder, or unspecified psychosis. They must be on a stable dose of antipsychotics for at least 30 days and able to consent. Exclusions include substance use disorders (except certain cases), intellectual disability, MRI contraindications, pregnancy, type 1 diabetes with complications, unstable medical conditions, neurological diseases affecting movement or seizures.

Inclusion Criteria

I have been diagnosed with a schizophrenia spectrum disorder.

I can understand and agree to the study's consent form.

I have been on a stable dose of antipsychotic medication for the last 30 days.

Exclusion Criteria

I have type 1 diabetes diagnosed before I was 35 or have had ketoacidosis.

I need a strong anxiety medication similar to or more than 2 mg/day of lorazepam.

I do not have any severe illnesses that could worsen my schizophrenia or make the treatment risky.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive iTBS (active or sham) five days per week for four consecutive weeks

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including fMRI scans and cognitive tests

6 months

2 visits (in-person)

Treatment Details

Interventions

• iTBS

Trial Overview The study tests if iTBS (a form of brain stimulation) applied to the DMPFC can improve social cognition in people with psychotic disorders compared to sham (fake) treatment. Participants will receive daily treatments for four weeks and undergo fMRI scans and cognitive assessments before treatment starts after it ends and six months later.

Participant Groups

Group I: Active iTBS Active Control 1 Intervention

Group II: Sham iTBS Placebo Group 1 Intervention

iTBS is already approved in United States for the following indications:

Approved in United States as iTBS for:

• Treatment-resistant depression
• Major depressive disorder

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

University of Maryland, Baltimore

Collaborator

Trials

729

Recruited

540,000+

Centre for Addiction and Mental Health

Collaborator

Trials

388

Recruited

84,200+

Wellcome Trust

Collaborator

Trials

236

Recruited

15,770,000+

Findings from Research

Intermittent theta-burst stimulation (iTBS) significantly improves hand function in stroke patients, particularly in those with higher baseline motor function and the presence of motor-evoked potentials (MEPs).

The study of 72 stroke patients showed that those with MEPs and better grip strength (Group A) had the greatest improvement in motor function, suggesting that iTBS effectiveness can be predicted by these factors, allowing for more tailored neurostimulation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. Lai, CJ., Wang, CP., Tsai, PY., et al.[2016]

In a study of 105 patients with treatment-resistant depression undergoing theta-burst stimulation, those taking antipsychotics did not have worse outcomes compared to those not on these medications, and some results even suggested better response and remission rates.

The findings indicate that the use of antipsychotics may not hinder the effectiveness of theta-burst stimulation, which is promising for patients who are on these medications, warranting further research into combined treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of antipsychotic pharmacotherapy on clinical outcomes of intermittent theta-burst stimulation for refractory depression. Schulze, L., Remington, G., Giacobbe, P., et al.[2018]

In a study involving 22 patients with treatment-resistant negative symptoms of schizophrenia, intermittent theta burst transcranial magnetic stimulation (iTBS) significantly reduced symptom severity compared to a sham treatment, with effects lasting up to 6 months after the sessions ended.

Neuroimaging results indicated that iTBS increased functional connectivity in the brain regions associated with dopamine transmission, suggesting that the therapeutic effects of iTBS may be linked to enhanced dopamine activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation for negative symptoms of schizophrenia-A double-blind, sham-controlled pilot study. Bation, R., Magnin, C., Poulet, E., et al.[2021]

Intermittent theta burst stimulation (iTBS) shows preliminary evidence of improving neurocognitive function in older adults with schizophrenia, based on a systematic review of two randomized controlled trials involving 132 participants.

While one trial demonstrated significant benefits of active iTBS over sham treatment, the other trial had inconsistent results, highlighting the need for further research with larger sample sizes to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Intermittent Theta Burst Stimulation for Neurocognitive Dysfunction in Older Adults with Schizophrenia. Zhang, X., Yang, X., Shi, Z., et al.[2023]

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

Accelerated intermittent Theta Burst Stimulation (iTBS) was found to be safe and well tolerated in a study of 50 treatment-resistant depressed patients, with no worsening of suicidal ideation observed during the treatment.

The study showed a significant decrease in suicide risk, as measured by the Beck Scale of Suicide Ideation, lasting up to one month after treatment, regardless of whether patients received active or sham stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial. Desmyter, S., Duprat, R., Baeken, C., et al.[2020]

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

Intermittent theta-burst stimulation (iTBS) and high-frequency rTMS (HF-rTMS) show similar efficacy in treating treatment-resistant depression (TRD), with response rates of 48.0% for iTBS and 45.5% for HF-rTMS based on two high-quality randomized controlled trials involving 474 participants.

Both iTBS and HF-rTMS have comparable safety profiles, with similar rates of discontinuation and adverse events, such as headaches, indicating that iTBS is a safe alternative to HF-rTMS for patients with TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. Lan, XJ., Yang, XH., Qin, ZJ., et al.[2023]

In a study involving 208 participants with treatment-resistant depression, both twice-daily and once-daily intermittent theta burst stimulation (iTBS) protocols showed improvements in depression scores, but there was no significant difference in efficacy between the two schedules after 10 and 30 days.

Response and remission rates were low in both treatment groups, indicating that neither protocol significantly accelerated the improvement of depressive symptoms in patients with treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study. Blumberger, DM., Vila-Rodriguez, F., Wang, W., et al.[2022]

Intermittent theta-burst stimulation (iTBS) shows promise as a targeted treatment for cognitive and psychosocial deficits following traumatic brain injury (TBI), potentially enhancing recovery when combined with behavioral interventions like cognitive rehabilitation and psychotherapy.

This review suggests that iTBS could lead to consistent functional gains in TBI patients, and future research may explore its application in other complex neuropsychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS/iTBS and Cognitive Rehabilitation for Deficits Associated With TBI and PTSD: A Theoretical Framework and Review. Lindsey, A., Ellison, RL., Herrold, AA., et al.[2023]

In a study of 22 participants with treatment-resistant depression, the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, which uses high-dose intermittent theta-burst stimulation (iTBS) guided by functional connectivity MRI, showed a remarkable remission rate of 90.5%.

The treatment was well tolerated with no negative cognitive side effects reported, suggesting that SAINT could be a safe and effective option for patients who have not responded to traditional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Cole, EJ., Stimpson, KH., Bentzley, BS., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of antipsychotic pharmacotherapy on clinical outcomes of intermittent theta-burst stimulation for refractory depression. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation for negative symptoms of schizophrenia-A double-blind, sham-controlled pilot study. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A Systematic Review of Intermittent Theta Burst Stimulation for Neurocognitive Dysfunction in Older Adults with Schizophrenia. [2023]

5. France pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

rTMS/iTBS and Cognitive Rehabilitation for Deficits Associated With TBI and PTSD: A Theoretical Framework and Review. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. [2020]