Theta Burst Stimulation for Alcoholism

(CDiA-P4 Trial)

Overseen By Daphne Voineskos, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must be taking: Antidepressants, SUD agonists

Must not be taking: Benzodiazepines, Anticonvulsants

Disqualifiers: Unstable illness, Pregnancy, Dementia, 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: 20

Duration: 4 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if intermittent theta burst stimulation (iTBS), a type of brain stimulation, can assist individuals with alcohol use disorder (AUD) who also experience depressive symptoms. iTBS targets the prefrontal cortex, a brain area associated with decision-making and mood, potentially improving both AUD and depression. Participants will receive either real iTBS or a sham (fake) version to compare effects. The trial seeks individuals diagnosed with AUD and depression, who have not recently used other substances, and can maintain their current medications throughout the study. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance treatment options for AUD and depression.

Will I have to stop taking my current medications?

You will need to keep your current antidepressant medications and medications for alcohol use disorder the same during the study. If you are on SUD agonist therapies, you should continue taking them as managed by your clinical team.

What prior data suggests that theta burst stimulation is safe for treating alcohol use disorders?

Research has shown that intermittent theta burst stimulation (iTBS) is generally safe. Studies have found that iTBS has a safety record similar to other repetitive transcranial magnetic stimulation (rTMS) treatments. For instance, one study found that iTBS was as safe as other common rTMS methods used to treat alcohol use disorder. Another study with veterans showed that iTBS was safely used, even for those with both post-traumatic stress disorder (PTSD) and alcohol use disorder.

Overall, these findings suggest that iTBS is well-tolerated by different groups, with no major side effects reported. This should reassure prospective participants that a trial using iTBS might involve minimal risk. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Theta Burst Stimulation (TBS) is unique because it targets the brain's dorsolateral prefrontal cortex (DLPFC) using magnetic pulses. Unlike standard alcoholism treatments, which often involve medications like disulfiram or naltrexone to manage cravings and withdrawal, TBS is non-invasive and focuses on brain activity. Researchers are excited about TBS because it offers a novel approach by potentially altering the brain's neural pathways involved in addiction, aiming for faster and more targeted relief without the side effects associated with traditional medications.

What evidence suggests that theta burst stimulation could be an effective treatment for alcoholism?

Research has shown that intermittent theta burst stimulation (iTBS) may help people with alcohol use disorders (AUD). In this trial, participants will receive either active iTBS or a sham stimulation as a control. Some studies have found that people with AUD who received iTBS showed better symptom improvement than those who received a sham treatment. For example, one study found that iTBS applied to a specific brain area improved treatment outcomes in veterans with AUD. Another study found that patients experienced faster improvement in depression symptoms when treated with real iTBS. These findings suggest that iTBS could be a useful tool for managing AUD, especially for those also experiencing depression. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-59 with alcohol use disorder (AUD) and major depressive disorder (MDD), without psychotic symptoms. Participants must be able to consent, adhere to the study schedule, maintain current medications constant, and not have used problematic substances other than nicotine or caffeine in the last month. Exclusions include dementia, significant medical or neurological disorders, non-English speakers, pregnancy intention during the study period, ECT failure history, metal implants near head or specific medication that affects rTMS efficacy.

Inclusion Criteria

Patients do not exhibit problematic use of any substances (excluding nicotine and caffeine), including alcohol, for >1 month

I am willing and able to agree to treatment.

Patients have a Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) diagnosis of AUD based on the MINI

Exclusion Criteria

Patients have possible or probable dementia based on cognitive assessments

Patients have a concomitant major unstable medical illness

I have a condition or take medication that could lead to severe depression or affect my thinking.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 20 treatments of active or sham repetitive transcranial magnetic stimulation (rTMS) over 4 weeks

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Theta Burst Stimulation
• Sham Stimulation

Trial Overview

The trial tests intermittent theta burst stimulation (iTBS), a form of transcranial magnetic stimulation targeting the prefrontal cortex to treat AUD with coexisting depressive symptoms. It compares iTBS against sham stimulation—a placebo-like treatment—to evaluate its effectiveness on cognitive functions disrupted by both conditions.

How Is the Trial Designed?

Group I: Active Bilateral Active Control 1 Intervention

Bilteral TBS, applied as cTBS over the right DLPFC followed by iTBS over the left DLPFC

Group II: Sham Placebo Group 1 Intervention

Sham TBS

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

Approved in United States as iTBS for:

• Treatment-resistant depression

Approved in European Union as iTBS for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Published Research Related to This Trial

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]

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 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) 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 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]

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]

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