Theta Burst Stimulation for Schizophrenia

(REDOCS Trial)

Overseen By Sabine Janssen

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Fabio Ferrarelli

Disqualifiers: Intellectual disorder, Neurologic disorder, Epilepsy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 week

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called intermittent Theta Burst Stimulation (iTBS) to determine its potential to improve brain function and memory in individuals with early-stage schizophrenia. Participants will receive either the actual treatment or a placebo, and then switch, to compare results. The researchers aim to discover if iTBS can enhance brain activity related to memory. Individuals who have experienced schizophrenia symptoms for less than three years might be suitable for this trial. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could lead to new treatments for schizophrenia.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that intermittent Theta Burst Stimulation (iTBS) is safe for early-course schizophrenia?

Research has shown that intermittent Theta Burst Stimulation (iTBS) is generally safe for people with schizophrenia. In various studies, participants mostly reported minor side effects such as mild headaches and scalp discomfort, which are common with this treatment. Serious side effects were rare.

One study compared iTBS with other similar brain stimulation methods and found it to be about as safe as the others. This indicates that for most people, iTBS does not cause major problems.

iTBS is a type of transcranial magnetic stimulation (TMS), which has already received approval for treating other conditions. This approval provides some confidence in its safety, although different conditions can have different effects.

Overall, evidence suggests that iTBS is safe for people, especially those with schizophrenia. Prospective trial participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about intermittent Theta Burst Stimulation (iTBS) for schizophrenia because it offers a novel, non-invasive approach compared to traditional antipsychotic medications. Unlike standard drugs that primarily target neurotransmitter imbalances, iTBS uses magnetic pulses to stimulate specific brain areas, potentially offering faster symptom relief. This method focuses on the left dorsolateral prefrontal cortex, a region linked to cognitive dysfunction in schizophrenia, which could lead to better cognitive outcomes. Additionally, the use of sham and active stimulation allows for a more rigorous assessment of iTBS's true efficacy, providing valuable insights into its potential as a new therapeutic tool.

What evidence suggests that intermittent Theta Burst Stimulation (iTBS) might be an effective treatment for schizophrenia?

Research shows that Intermittent Theta Burst Stimulation (iTBS) can improve symptoms in people with schizophrenia. In this trial, participants will receive either active iTBS followed by sham iTBS, or sham iTBS followed by active iTBS. Studies have found that iTBS may reduce negative symptoms, such as lack of motivation or social withdrawal, and improve social thinking. Other research supports that iTBS is safe and effectively targets brain areas involved in these symptoms. Overall, this treatment shows promise for enhancing certain brain functions related to schizophrenia. ^{2 3 6 7 8}

Who Is on the Research Team?

Fabio Ferrarelli, MD, PhD

Principal Investigator

University of Pittsbrugh

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-40 with early-course schizophrenia, having experienced psychosis for less than three years. Participants must have a diagnosis within the Schizophrenia Spectrum and be able to give informed consent. It's not open to those who are pregnant or recently postpartum, have diabetes with certain complications, significant neurological disorders, substance dependence (except cannabis/alcohol), or a history of severe head injury.

Inclusion Criteria

I have been diagnosed with a schizophrenia spectrum disorder.

Duration of less than three years from beginning of psychosis, defined by report of symptoms and/or history of treatment, based on clinical guidelines employed in UPMC psychoses clinics in Pittsburgh.

Exclusion Criteria

DSM intellectual developmental disorder

Inability to provide informed consent

I have a medical condition that affects my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intermittent Theta Burst Stimulation (iTBS) and sham TBS over the dorsolateral prefrontal cortex (DLPFC) to assess changes in oscillatory activity and working memory performance

1 week

2 visits (in-person)

Follow-up

Participants are monitored for changes in DLPFC oscillatory activity and working memory performance post-treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Theta Burst Stimulation (iTBS)

Trial Overview The study tests if Theta Burst Stimulation (iTBS) can improve brain function and memory in people with early schizophrenia. iTBS uses magnetic pulses on the brain while EEG tracks activity changes. Participants will receive either real iTBS or a sham treatment without active stimulation to compare effects on working memory.

How Is the Trial Designed?

Group I: sham, then active intermittent Theta Burst Stimulation (iTBS) over DLPFC Experimental Treatment 2 Interventions

This arm will first receive sham iTBS (i.e., with the TMS coil in the placebo orientation) and then active iTBS stimulation over the left dorsolateral prefrontal cortex (DLPFC).

Group II: active, then sham Intermittent Theta Burst Stimulation (iTBS) over DLPFC Experimental Treatment 2 Interventions

This arm will first receive active iTBS stimulation and then sham iTBS over the left dorsolateral prefrontal cortex (DLPFC).

Intermittent Theta Burst Stimulation (iTBS) is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Migraines
• Smoking Cessation

Approved in European Union as rTMS for:

• Major Depressive Disorder (MDD)

Who Is Running the Clinical Trial?

Fabio Ferrarelli

Lead Sponsor

Trials

2

Recruited

280+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

This study is a randomized, sham-controlled, double-blind trial involving 86 patients with schizophrenia spectrum disorder, testing the efficacy of continuous theta burst stimulation (cTBS) on reducing auditory verbal hallucinations (AH).

The primary goal is to measure the reduction in AH symptoms using the PSYRATS-AH score after treatment, with follow-up assessments at 1, 3, and 6 months, which will help determine the effectiveness of cTBS compared to sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of auditory hallucinations with bilateral theta burst stimulation (cTBS): protocol of a randomized, double-blind, placebo-controlled, multicenter trial. Plewnia, C., Brendel, B., Schwippel, T., et al.[2018]

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]

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) 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 of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., et al.[2022]

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]

In a study of 60 patients with treatment-resistant unipolar depression, both intermittent theta burst stimulation (iTBS) and conventional 10 Hz rTMS showed similar efficacy in reducing depression scores and improving quality of life over a 6-month follow-up, with response rates of 36.7% for iTBS and 33.3% for rTMS.

iTBS is highlighted as a more time-efficient and cost-effective option compared to rTMS, suggesting it could be a valuable treatment alternative for patients with severe depression who have not responded to multiple antidepressant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). Bulteau, S., Laurin, A., Pere, M., et al.[2022]

This clinical trial will compare the effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and intermittent theta burst stimulation (iTBS) on negative symptoms of schizophrenia in 90 patients, aiming to provide a new treatment option for this challenging condition.

The study will also explore the impact of these treatments on depressive symptoms, cognitive performance, and smoking behavior, while using MRI and EEG to identify potential neural markers for treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN). Hebel, T., Langguth, B., Schecklmann, M., et al.[2022]

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]

Theta burst stimulation (TBS) is a promising therapeutic approach for schizophrenia, showing potential benefits in treating specific symptoms and improving patient insight, based on a review of 30 studies that utilized various neuroimaging techniques.

TBS is well-tolerated and has few adverse effects, making it a feasible option for augmenting traditional pharmacotherapy in patients with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of theta burst stimulation in patients with schizophrenia - A systematic review. Poorganji, M., Goeke, K., Zomorrodi, R., et al.[2023]

In a study involving 36 patients with treatment-resistant schizophrenia, intermittent theta burst stimulation (iTBS) targeting the midline cerebellum did not show significant improvements in schizophrenia symptoms compared to sham stimulation, indicating limited efficacy for this approach.

The iTBS treatment was found to be safe and well tolerated, with no major side effects reported, suggesting that while it may not be effective, it does not pose significant risks to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Intensive Cerebellar Intermittent Theta Burst Stimulation (iCiTBS) in Treatment-Resistant Schizophrenia: a Randomized Placebo-Controlled Study. Chauhan, P., Garg, S., Tikka, SK., et al.[2021]

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