Theta Burst Stimulation for Alcoholism

(CDiA-P4 Trial)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

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

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The prefrontal cortex, although well established as an efficacious target for the treatment of major depressive disorder (MDD), has recently come into favour as a therapeutic target for alcohol use disorders (AUD). Depressive symptoms are also highly prevalent in individuals with AUD. A number of cognitive and psychological processes stemming from the prefrontal cortex, a common treatment target for repetitive transcranial magnetic stimulation (rTMS), are disrupted in both MDD and AUD. The proposed study will enhance the development of theta burst stimulation (TBS) as a new intervention for AUD in the context of depressive symptoms and uses integrated TMS-EEG to identify neurophysiological targets of executive dysfunction in this disorder.

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 data supports the effectiveness of this treatment for alcoholism?

Intermittent theta burst stimulation (iTBS) is a promising treatment for alcohol use disorder, as it has shown similar effectiveness to other established treatments for depression and has been suggested to reduce brain reactivity to alcohol cues, potentially decreasing drinking behavior. ^{1 2 3 4 5}

Is theta burst stimulation safe for humans?

Research shows that intermittent theta burst stimulation (iTBS) is generally safe and well-tolerated in humans, with no adverse events reported in studies involving patients with bipolar depression and treatment-resistant depression. ^{2 3 5 6 7}

How is the treatment Intermittent Theta Burst Stimulation (iTBS) different from other treatments for alcohol use disorder?

Intermittent Theta Burst Stimulation (iTBS) is a unique treatment for alcohol use disorder because it uses a non-invasive technique called repetitive transcranial magnetic stimulation (rTMS) to target specific brain areas, potentially reducing cravings and brain reactivity to alcohol cues. Unlike traditional rTMS, iTBS sessions are much shorter, lasting only about 3 minutes, which may improve patient comfort and adherence. ^{1 2 3 5 7}

Eligibility Criteria

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 screened positive for a Major Depressive Episode (MDE) based on the MINI without psychotic symptoms

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.

Trial Timeline

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

Treatment Details

Interventions

• Intermittent Theta Burst Stimulation (Behavioural Intervention)
• Sham Stimulation (Behavioural Intervention)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

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]

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]

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]

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) 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) 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]

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. 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]

3. 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]

4. 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]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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