Neuromodulation for Obsessive-Compulsive Disorder

Overseen By Robert Reinhart, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Boston University Charles River Campus

Disqualifiers: Bipolar, Psychotic disorders, Tourette, 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: Unknown

Duration: 5 days

90 Participants Needed

Trial Summary

What is the purpose of this trial?

Although multiple treatments for OCD exist, slow symptom decrease, high remission, and significant side effects for some OCD patients limit their efficacy. More research into the precise neural mechanisms and linked cognitive functions in OCD is also necessary. To address both concerns, this study by Dr. Reinhart and his team will test a new, non-invasive, and well-tolerated neuromodulation method for reducing OCD symptoms, based on reward-related rhythms of the orbitofrontal cortex (OFC; a brain region responsible for reward, decision making and other crucial functions that is affected by OCD). This proposal is based on highly encouraging preliminary data in both subsyndromal and treatment-resistant populations that shows rapid reductions in OCD behaviors that last at least 1-3 months. Using high-definition transcranial alternating current stimulation (HD-tACS) guided by EEG brain wave recordings, the study will test whether repetitive modulation of relevant rhythm activity in the OFC can lead to rapid (within five days) and sustainable (up to three months) OCD symptom reduction. This research aims to increase knowledge of OCD and development of effective treatment with minimal side effects.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that there have been no changes to your OCD medication or therapy in the last 3 months. This suggests you should continue your current treatment without changes.

What data supports the effectiveness of the treatment High Definition Transcranial Alternating Current Stimulation (HD-tACS) for Obsessive-Compulsive Disorder?

Research on a similar treatment, transcranial direct current stimulation (tDCS), shows it can reduce symptoms in patients with treatment-resistant OCD. For example, one study found a 26% reduction in symptoms after using tDCS, suggesting that non-invasive brain stimulation techniques like HD-tACS might also be effective. ^{1 2 3 4 5}

Is transcranial alternating current stimulation (tACS) safe for humans?

Research indicates that transcranial alternating current stimulation (tACS) is generally safe and well-tolerated in humans, with no severe adverse events reported in studies, including those involving people with major depressive disorder. Mild side effects like tinnitus (ringing in the ears) have been noted, but these are not serious. ^{6 7 8 9 10}

How is HD-tACS different from other treatments for OCD?

HD-tACS is a unique treatment for OCD because it uses alternating electrical currents to modulate brain activity non-invasively, targeting specific brain areas involved in OCD, unlike traditional medications or therapies that may not directly target these brain circuits. ^{4 11 12 13 14}

Eligibility Criteria

This trial is for adults with OCD who score at least 16 on the YBOCS, can consent to participate, and follow study rules. It's not for those with severe depression, pregnancy, metal head implants, electronic devices in body, vision issues despite correction, claustrophobia or neurological disorders like epilepsy.

Inclusion Criteria

I have been diagnosed with OCD.

Score of 16 or greater on the YBOCS

I am 18 years old or older.

Exclusion Criteria

I have severe depression.

Suicidal risk as determined by moderate or greater score on the Columbia Suicide Severity Rating Scale (C-SSRS)

Organic brain syndrome, mental retardation, or other potentially interfering cognitive dysfunction

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high-definition transcranial alternating current stimulation (HD-tACS) guided by EEG brain wave recordings to modulate orbitofrontal cortex activity

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• High Definition Transcranial Alternating Current Stimulation

Trial Overview The study tests a new non-invasive neuromodulation technique using HD-tACS guided by EEG to reduce OCD symptoms quickly (within five days) and sustainably (up to three months). The focus is on modulating brain rhythms in the OFC that are linked with reward and decision-making.

Participant Groups

Group I: Active HD-tACS Active Control 1 Intervention

HD-tACS of OFC

Group II: Sham HD-tACS Placebo Group 1 Intervention

HD-tACS of OFC

High Definition Transcranial Alternating Current Stimulation is already approved in United States for the following indications:

Approved in United States as HD-tACS for:

• Obsessive-compulsive disorder (OCD) - Research and experimental use

Who Is Running the Clinical Trial?

Boston University Charles River Campus

Lead Sponsor

Trials

125

Recruited

14,100+

Findings from Research

In a clinical trial involving 21 treatment-resistant OCD patients, cathodal transcranial direct current stimulation (tDCS) over the supplementary motor area showed a significant reduction in obsessive-compulsive symptoms after one month, with 24% of patients meeting the criteria for treatment response.

The treatment was well tolerated, with only mild side effects like tingling and skin redness reported, indicating that tDCS could be a safe and promising option for patients who do not respond to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating refractory obsessive-compulsive disorder with transcranial direct current stimulation: An open label study. Harika-Germaneau, G., Heit, D., Chatard, A., et al.[2021]

In a study of 32 patients with treatment-resistant obsessive-compulsive disorder (OCD), 28% showed at least a partial response to transcranial direct current stimulation (tDCS) after 10-20 sessions.

Among the responders, 25% had a significant improvement, suggesting that tDCS could be a beneficial treatment option for some individuals who do not respond to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for treatment-resistant obsessive-compulsive disorder-A large case series. Thamby, A., Seshachala, K., Sharma, L., et al.[2021]

In a study involving 21 patients with treatment-resistant OCD, transcranial direct current stimulation (tDCS) showed a significant reduction in OCD symptoms immediately after treatment compared to sham stimulation.

However, the effects of tDCS did not persist, as there were no significant differences in symptom reduction observed one and three months after the treatment, indicating that while tDCS may provide short-term relief, it does not lead to long-lasting improvements in OCD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in patients with obsessive compulsive disorder: A randomized controlled trial. Bation, R., Mondino, M., Le Camus, F., et al.[2020]

A case study of a patient with treatment-resistant OCD showed that 10 sessions of cathodal transcranial direct current stimulation (c-tDCS) over the left orbitofrontal cortex led to a 26% reduction in obsessive and compulsive symptoms, indicating potential efficacy.

The treatment was safe, with no adverse events reported, suggesting that c-tDCS could be a viable option for patients who do not respond to traditional OCD therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Cathodal Transcranial Direct Current Stimulation Over the Left Orbitofrontal Cortex in a Patient With Treatment-Resistant Obsessive-Compulsive Disorder. Mondino, M., Haesebaert, F., Poulet, E., et al.[2022]

A case study of a 33-year-old woman with treatment-resistant OCD showed that cathodal transcranial direct current stimulation (tDCS) over the presupplementary motor area (pre-SMA) led to a significant 30% reduction in OCD symptoms after 20 sessions, suggesting its potential as a treatment option.

The initial anodal stimulation worsened OCD symptoms, indicating that the pre-SMA may be hyperactive in OCD, and that inhibitory stimulation (cathodal) could be necessary to alleviate symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polarity-dependent effects of transcranial direct current stimulation in obsessive-compulsive disorder. D'Urso, G., Brunoni, AR., Anastasia, A., et al.[2022]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

In a pilot study involving 30 drug-naive adults with major depressive disorder, transcranial alternating current stimulation (tACS) at 77.5 Hz and 15 mA showed a significant remission rate of 10 out of 15 patients at week 8, compared to only 3 out of 15 in the sham group.

The tACS treatment was well-tolerated with no severe adverse events reported, indicating it is a safe and acceptable intervention for treating depressive symptoms in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A pilot study of transcranial alternating current stimulation in the treatment of drug-naive adult patients with major depressive disorder]. Wang, HX., Wang, K., Sun, ZC., et al.[2020]

Transcranial Direct Current Stimulation (tDCS) is generally considered safe, but there are concerns that it could lead to significant negative effects in healthy individuals.

The scientific community needs to be alerted about the potential risks of tDCS, emphasizing the importance of protecting healthy volunteers from possible harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. Boccard-Binet, S., Sen, A.[2021]

In a study involving 43 patients with treatment-resistant OCD, transcranial direct current stimulation (tDCS) significantly reduced OCD symptoms compared to sham treatment, with an average decrease in Y-BOCS scores of 6.68 points for active tDCS versus 2.84 points for sham.

While tDCS was effective in reducing OCD symptoms, it did not show superiority in alleviating symptoms of depression or anxiety, and both groups reported only mild adverse events, indicating a good safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of transcranial direct current stimulation as an add-on treatment for obsessive-compulsive disorder: a randomized, sham-controlled trial. Silva, RMFD., Brunoni, AR., Goerigk, S., et al.[2023]

This feasibility study involves 25 adults with OCD and aims to assess the acceptability and safety of transcranial direct current stimulation (tDCS) as a treatment, focusing on two stimulation sites: the orbitofrontal cortex (OFC) and the supplementary motor area (SMA).

The study will evaluate the effectiveness of tDCS on OCD symptoms and gather qualitative data on participants' experiences, which will help refine the methodology for a larger trial, indicating potential for tDCS as a self-administered intervention for OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and acceptability of transcranial stimulation in obsessive-compulsive symptoms (FEATSOCS): study protocol for a randomised controlled trial of transcranial direct current stimulation (tDCS) in obsessive-compulsive disorder (OCD). Cinosi, E., Adam, D., Aslan, I., et al.[2021]

Transcranial direct current stimulation (tDCS) is a promising non-invasive treatment for patients with treatment-resistant obsessive-compulsive disorder (OCD), as shown in a clinical trial design involving 44 participants.

In initial case reports, one patient experienced significant improvement in OCD symptoms after tDCS treatment, while another did not respond, indicating variability in treatment efficacy; however, tDCS was well tolerated overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for treatment-resistant obsessive-compulsive disorder: report on two cases and proposal for a randomized, sham-controlled trial. Silva, RM., Brunoni, AR., Miguel, EC., et al.[2022]

Neuromodulation techniques like deep brain stimulation, transcranial magnetic stimulation, and electroconvulsive therapy are emerging as promising treatments for obsessive-compulsive disorder (OCD), especially for patients who do not respond to standard therapies.

These treatments target specific brain circuits involved in OCD, such as the basal ganglia and cortico-striato-thalamo-cortical loops, suggesting a mechanistic approach to improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation for obsessive-compulsive disorder. Lapidus, KA., Stern, ER., Berlin, HA., et al.[2021]

Transcranial direct current stimulation (tDCS) shows potential as a treatment for obsessive-compulsive disorder (OCD), particularly with a montage that places the cathode over the pre-supplementary motor area, which may effectively target brain areas involved in OCD.

The study reviewed existing literature on repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS) for OCD, using computer modeling to suggest optimal electrode placements for future tDCS trials, although further empirical validation is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in obsessive-compulsive disorder: emerging clinical evidence and considerations for optimal montage of electrodes. Senço, NM., Huang, Y., D'Urso, G., et al.[2022]

References

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

Treating refractory obsessive-compulsive disorder with transcranial direct current stimulation: An open label study. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for treatment-resistant obsessive-compulsive disorder-A large case series. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in patients with obsessive compulsive disorder: A randomized controlled trial. [2020]

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

Efficacy of Cathodal Transcranial Direct Current Stimulation Over the Left Orbitofrontal Cortex in a Patient With Treatment-Resistant Obsessive-Compulsive Disorder. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Polarity-dependent effects of transcranial direct current stimulation in obsessive-compulsive disorder. [2022]

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

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]

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

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

8. China pubmed.ncbi.nlm.nih.gov

[A pilot study of transcranial alternating current stimulation in the treatment of drug-naive adult patients with major depressive disorder]. [2020]

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

Safety of transcranial direct current stimulation in healthy participants. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of transcranial direct current stimulation as an add-on treatment for obsessive-compulsive disorder: a randomized, sham-controlled trial. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Feasibility and acceptability of transcranial stimulation in obsessive-compulsive symptoms (FEATSOCS): study protocol for a randomised controlled trial of transcranial direct current stimulation (tDCS) in obsessive-compulsive disorder (OCD). [2021]

12. Brazil pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for treatment-resistant obsessive-compulsive disorder: report on two cases and proposal for a randomized, sham-controlled trial. [2022]

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

Neuromodulation for obsessive-compulsive disorder. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in obsessive-compulsive disorder: emerging clinical evidence and considerations for optimal montage of electrodes. [2022]