iTBS for Alcoholism

Overseen By Erin Deneke, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Nicholas Balderston, PhD

Disqualifiers: Neurological disorders, Seizures, Pacemaker, 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: 5

Duration: 1 week

42 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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

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

Research suggests that iTBS, a type of brain stimulation, may help reduce alcohol cravings and brain responses to alcohol cues, similar to its effects in treating depression. A study showed that iTBS can decrease drinking behavior in people with alcohol use disorder. ^{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 conditions like bipolar depression and treatment-resistant depression. ^{3 6 7 8 9}

How is iTBS treatment different from other treatments for alcoholism?

iTBS (Intermittent Theta Burst Stimulation) is a non-invasive brain stimulation technique that is quicker and potentially more tolerable than traditional methods, like repetitive transcranial magnetic stimulation (rTMS), and is being explored for its ability to reduce alcohol cravings by targeting specific brain areas. ^{1 2 3 9 10}

What is the purpose of this trial?

The two primary objectives of this study are to test whether intermittent theta-burst (iTBS) can affect behavioral change as compared to treatment as usual (TAU, sham) in individuals with alcohol use disorder (AUD) in inpatient substance use treatment. The secondary objective is to determine whether iTBS reduces the risk for relapse at four months compared to sham. It is hypothesized that individuals who receive iTBS treatment will show attenuated prefrontal cortex (PFC) CNS responses to alcohol related cues and reductions in risk-taking behavior and impulsivity as measured by PFC responses measured by functional near infrared spectroscopy (fNIRs). The proposed approach will be to measure the effect of iTBS treatment on PFC CNS response. Participants will be randomized to receive 5 days (4 x sessions/day x 600 pulses/session = 12,000 pulses) of iTBS or sham to the left dorsal lateral prefrontal cortex (dlPFC) while being exposed to alcohol cues five minutes prior to treatment and during treatment. The investigators will target the Beam/F3 scalp location and use the TMS Navigator Research Premium stereotaxic system for neuronavigation. PFC response data will be gathered using fNIRs measuring cue reactivity, risk-taking (Balloon Analog Risk Test), and impulsiveness (Go No Go task). The primary outcomes will be the mean changes in pre-post PFC response data gathered using the fNIRs sessions. The rationale for this approach is that TBS can be delivered over a shorter time frame than rTMS and may require fewer sessions, allowing for a better fit within a 28-day inpatient treatment stay.

Eligibility Criteria

This trial is for individuals with alcohol use disorder (AUD) who are currently in inpatient substance use treatment. Participants should be willing to undergo a type of brain stimulation therapy called iTBS or a sham treatment as part of the study.

Inclusion Criteria

Provision of signed and dated informed consent form

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

I am diagnosed with AUD and will be in residential treatment for at least 28 days.

Exclusion Criteria

I am not pregnant, planning to become pregnant, breastfeeding, and I am willing to use contraception.

I have undergone TMS therapy before.

I have a significant neurological disorder or history of seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive intermittent theta-burst stimulation (iTBS) or sham treatment for 5 days, with 4 sessions per day

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of cue reactivity, risk-taking, and impulsiveness

4 months

Treatment Details

Interventions

• iTBS

Trial Overview The study tests if intermittent theta-burst (iTBS) can change behavior and reduce relapse risk in AUD patients compared to usual treatments. It involves exposing participants to alcohol cues while receiving iTBS or sham treatments targeting the prefrontal cortex, measured by brain response.

Participant Groups

Group I: Active iTBS Experimental Treatment 1 Intervention

The intermittent theta burst (iTBS) will be delivered using the MagVenture MagPro X100 stimulator equipped with a Cool B-70 A/P (combined active \& sham) figure of eight coil. Treatment will be at 100% of MT. Treatment will be approximately 2 ½ minutes long. Each session will be 2-hours in length and consist of four treatments spaced 30 minutes apart. There will be a total of five sessions over the course of five to seven days.

Group II: Sham iTBS Placebo Group 1 Intervention

The B70 A/P coil is also equipped with an active sham electric stimulation (e-stim) system that delivers a small current pulse synchronous to the TMS pulse, titrated to match the TMS sensations. This pulse is similar in duration and distribution to the current induced by the TMS pulse . This pulse will be delivered to the scalp adjacent to the stimulation site via disposable low-profile webbed EEG electrodes filled with electrolytic gel. Electrodes will be connected to the e-stim system via one of two identical cables allowing the operator to deliver either real or sham electric stimulation. Cables will be labeled to match the corresponding coil side so that each session always includes either active TMS or active e-stim, but never both.

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?

Nicholas Balderston, PhD

Lead Sponsor

Trials

2

Recruited

240+

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 clinical trial with 50 individuals suffering from alcohol use disorder (AUD), continuous theta burst stimulation (TBS) to the medial prefrontal cortex significantly reduced drinking behavior and brain reactivity to alcohol cues for up to 3 months after treatment.

Participants receiving real TBS were 2.71 times more likely to stay in the study and 3.09 times more likely to remain sober compared to those receiving sham treatment, indicating the potential efficacy of TBS as a therapeutic intervention for AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medial Prefrontal Cortex Theta Burst Stimulation Improves Treatment Outcomes in Alcohol Use Disorder: A Double-Blind, Sham-Controlled Neuroimaging Study. McCalley, DM., Kaur, N., Wolf, JP., et al.[2023]

A randomized controlled trial involving 60 patients with alcohol use disorder is investigating the efficacy of intermittent theta burst stimulation (iTBS) on reducing cravings, targeting the left dorsolateral prefrontal cortex (DLPFC).

The study aims to determine if iTBS can effectively decrease craving levels, as measured by visual analogue scale (VAS) scores, and if successful, it could offer a tolerable and accessible treatment option for alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Intermittent Theta Burst Stimulation (iTBS) in Patients With Alcohol Use Disorder: Study Protocol for a Randomized Controlled Trial. Yuan, C., Su, H., Chen, T., et al.[2022]

Accelerated, high-dose intermittent theta burst stimulation (iTBS) showed promising results in treating highly treatment-resistant depression, with most patients achieving remission after treatment.

However, the effects were short-lived, as all patients experienced relapse within two weeks, indicating a need for improved treatment strategies that enhance the durability of the therapeutic response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is accelerated, high-dose theta burst stimulation a panacea for treatment-resistant depression? Caulfield, KA.[2021]

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]

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]

Intermittent theta burst stimulation (iTBS) was found to be safe for veterans with PTSD, even those with mild alcohol use disorder (AUD), although AUD patients reported more adverse events.

Patients with comorbid AUD who received active iTBS showed greater improvement in depression symptoms compared to those without AUD, while the presence of AUD did not affect changes in PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation in Veterans with Mild Alcohol Use Disorder. Bozzay, ML., Brigido, S., van 't Wout-Frank, M., et al.[2022]

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]

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 of 71 participants with Major Depressive Disorder who had limited response to high-frequency left-sided stimulation, subthreshold intensity intermittent theta-burst stimulation priming (iTBS-P) led to a greater reduction in depressive symptoms compared to suprathreshold intensity stimulation.

The results suggest that iTBS-P may work through homeostatic plasticity mechanisms, indicating that lower intensity stimulation could be more effective for clinical improvement in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder. Lee, JC., Corlier, J., Wilson, AC., et al.[2021]

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

Medial Prefrontal Cortex Theta Burst Stimulation Improves Treatment Outcomes in Alcohol Use Disorder: A Double-Blind, Sham-Controlled Neuroimaging Study. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The Effect of Intermittent Theta Burst Stimulation (iTBS) in Patients With Alcohol Use Disorder: Study Protocol for a Randomized Controlled Trial. [2022]

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

Is accelerated, high-dose theta burst stimulation a panacea for treatment-resistant depression? [2021]

5. United States 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). [2022]

6. France pubmed.ncbi.nlm.nih.gov

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation in Veterans with Mild Alcohol Use Disorder. [2022]

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

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

9. 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]

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

Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder. [2021]