Brain Stimulation for Stress

(NUMBER Trial)

Overseen By Thomas E Kraynak, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must not be taking: Antihypertensives, Anticonvulsants, Antipsychotics, others

Disqualifiers: Epilepsy, Heart disease, Cancer, others

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

Compensation: Varies

Number of Visits: 3

Duration: 2 visits

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a type of brain stimulation can alter emotional responses to stress. Participants will undergo transcranial magnetic stimulation (TMS), a non-invasive and temporary technique. During the trial, participants will receive both real (active continuous theta burst stimulation) and sham (pretend continuous theta burst stimulation) to compare effects. Individuals who have lived in Pittsburgh for at least six weeks and are comfortable undergoing an MRI may be suitable for this study. As an unphased trial, this study offers participants a unique opportunity to contribute to pioneering research in brain stimulation and emotional health.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications to participate in this trial. The study excludes participants who have used specific medications, like heart or brain-related drugs, in the past 14 days. If you've stopped a disallowed medication for at least a month, you may still be eligible.

What prior data suggests that this brain stimulation technique is safe?

Research has shown that continuous theta burst stimulation (cTBS), a type of non-invasive brain treatment, is generally safe. Studies have found that cTBS is well-tolerated and can help with issues like anxiety and auditory hallucinations. Although it is a newer method, most participants in research trials experience only mild or no side effects. This suggests that cTBS could be a safe way to study its effects on stress in healthy individuals. However, due to its relative novelty, researchers carefully monitor participants during studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the brain stimulation technique called continuous theta burst stimulation (cTBS) because it offers a non-invasive approach to managing stress, unlike traditional methods that often rely on medication or therapy. This treatment uses magnetic fields to stimulate specific areas of the brain, potentially providing faster relief from stress symptoms. While most treatments for stress involve long-term medication with possible side effects, cTBS could offer a quicker, more targeted alternative with fewer side effects. The trial is exploring both active and sham stimulations, which will help determine the true effectiveness of this innovative approach.

What evidence suggests that this trial's treatments could be effective for stress?

This trial will compare the effects of active continuous theta burst stimulation (cTBS) with sham cTBS on stress. Studies have shown that cTBS can affect brain activity. For example, research indicates that cTBS can improve symptoms in conditions like schizophrenia. Another study found that cTBS helped people recover better after a stroke. These findings suggest that cTBS might have various positive effects on brain function. While this research doesn't specifically focus on stress, it offers hope that cTBS might help manage emotional responses in stressful situations. ^{3 4 6 7 8}

Who Is on the Research Team?

Thomas E Kraynak, PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for healthy individuals interested in how brain stimulation might affect their emotional response to stress. Participants should be willing to undergo MRI scans and two sessions of transcranial magnetic stimulation (TMS), one active and one sham.

Inclusion Criteria

I am between 30 and 50 years old.

English language proficiency (English as the primary language used in the home for the past 10 years)

Report that they will reside in the Pittsburgh area for at least 6 weeks, to maintain scheduling availability

Exclusion Criteria

Substance use: excessive alcohol consumption and illicit drug use

I regularly take more than 2 non-insulin diabetes medications.

I have been taking certain medications regularly for the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Assessment

Participants perform a series of tasks while completing an MRI scan

1 day

1 visit (in-person)

Treatment

Participants undergo transcranial magnetic stimulation (TMS) with active and sham stimulation at two visits

2 visits

2 visits (in-person)

Follow-up

Participants are monitored for changes in arousal, valence, perceived control, and physiological responses post-stimulation

30-60 minutes post-stimulation

What Are the Treatments Tested in This Trial?

Interventions

• Active continuous theta burst stimulation
• Sham continuous theta burst stimulation

Trial Overview The study tests the effects of a non-invasive brain stimulation technique called continuous theta burst stimulation on managing stress and anxiety. It involves comparing active TMS with a placebo-like 'sham' version while participants complete tasks during an MRI scan.

How Is the Trial Designed?

Group I: Sham then Active Experimental Treatment 2 Interventions

In this arm, participants will first undergo sham theta burst stimulation (cTBS) at the first visit and then undergo active cTBS in the second visit.

Group II: Active then Sham Experimental Treatment 2 Interventions

In this arm, participants will first undergo active theta burst stimulation (cTBS) at the first visit and then undergo sham cTBS in the second visit.

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In a study of 60 treatment-refractory patients with major depressive disorder, both intermittent and combined theta-burst stimulation showed significantly better antidepressant responses compared to continuous theta-burst stimulation and sham treatment after 2 weeks.

Theta-burst stimulation is well-tolerated and effective, especially in patients with lower levels of treatment refractoriness, indicating that the severity of refractoriness can influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. Li, CT., Chen, MH., Juan, CH., et al.[2022]

In a randomized, double-blind trial involving 56 patients, intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex showed a significant reduction in negative symptoms for patients with depression, but not for those with schizophrenia.

The treatment was generally safe and well-tolerated, with serious adverse events occurring only in the sham group, indicating that iTBS may be a promising intervention for depressive symptoms in certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. Bodén, R., Bengtsson, J., Thörnblom, E., et al.[2021]

In a study involving 20 healthy participants over five days, daily intermittent theta burst stimulation (iTBS) did not show any significant cumulative increase in cortical excitability compared to sham stimulation, suggesting that repeated sessions may not enhance therapeutic effects as previously believed.

The results indicate high variability in individual responses to both active and sham iTBS, with no consistent pattern of improvement, which raises questions about the effectiveness of iTBS in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar effect of intermittent theta burst and sham stimulation on corticospinal excitability: A 5-day repeated sessions study. Perellón-Alfonso, R., Kralik, M., Pileckyte, I., et al.[2022]

Continuous theta burst stimulation (cTBS) effectively inhibits synaptic transmission in the primary motor cortex for up to 1 hour, demonstrating its potential as a novel neuromodulation technique.

cTBS applied to the left motor cortex increases local GABA levels, indicating enhanced GABAergic activity, while not significantly affecting glutamate/glutamine levels, suggesting a specific mechanism of action for this stimulation technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. Stagg, CJ., Wylezinska, M., Matthews, PM., et al.[2022]

In a study involving 34 healthy female participants, the effectiveness of intermittent theta burst stimulation (iTBS) on reducing stress was linked to the resting-state functional connectivity (rsFC) between the left dorsolateral prefrontal cortex (DLPFC) and the caudal anterior cingulate cortex (ACC).

Participants with a stronger negative correlation in rsFC experienced a greater reduction in stress sensitivity after active iTBS, suggesting that individual brain connectivity patterns could help tailor and improve the treatment's effectiveness for stress-related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individual resting-state frontocingular functional connectivity predicts the intermittent theta burst stimulation response to stress in healthy female volunteers. de Wandel, L., Pulopulos, MM., Labanauskas, V., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8979658/

Clinical effects of continuous theta burst stimulation for ... The purpose of this study was to compare the clinical effects and α oscillations induced by cTBS versus 1 Hz rTMS as predictors of response.

2. sciencedirect.com sciencedirect.com/science/article/pii/S016503272401509X

Optimizing antidepressant benefits: Effect of theta burst ... This study explores whether individuals meeting minimum recommended physical activity levels demonstrate better responses to TBS compared to physically ...

3. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.123.042924

Continuous Theta-Burst Stimulation of the Contralesional ... Active cTBS was associated with better scores on the modified Rankin Scale at 3 months (OR, 0.2 [95% CI, 0.1–0.8]; P=0.0225) and with an 18 days ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2825296

Theta Burst Stimulation Protocols for Schizophrenia The primary outcome of this study was improvement in scores related to negative symptoms (Scale for the Assessment of Negative Symptoms [SANS] ...

5. link.springer.com link.springer.com/article/10.1007/s00221-025-07040-9

Testing the effectiveness of combined attention ... The aim of this feasibility study was the evaluation of the effectiveness of cTBS over the right DLPFC combined with Attention Modification Training (AMT) on ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3260517/

Safety of Theta Burst Transcranial Magnetic Stimulation Based on this review, TBS appears to be a safe and efficacious technique. However, given its novelty, it should be applied with caution.

7. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1446849/full

The efficacy and safety of continuous theta burst ... Preliminary findings have suggested that cTBS therapy may yield positive results in improving auditory hallucination and minimizing adverse ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032722006310

The functional connectivity predictor of therapeutic effect of ... cTBS intervention on bilateral SMA can significantly improve the symptoms of medicated OCD patients with moderate severity.