Ketamine for Obsessive-Compulsive Disorder

(MKET2 Trial)

Overseen By Carolyn I Rodriguez, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Psychotropic, Naltrexone, Ketamine

Disqualifiers: Pregnancy, Metal in body, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how ketamine can reduce symptoms of obsessive-compulsive disorder (OCD). Participants will be divided into two groups: one will receive ketamine with naltrexone, and the other will receive ketamine with a placebo (a non-active substance). The study aims to assess the treatments' effects on the brain using fMRI scans. Individuals diagnosed with OCD, who have not responded to standard treatments, and can follow specific study guidelines might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in OCD treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you must commit to medication study procedures, which might involve changes to your medication routine.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ketamine might quickly reduce symptoms of obsessive-compulsive disorder (OCD). Some studies found that patients experienced a significant decrease in symptoms soon after taking ketamine. However, the FDA has not yet approved ketamine specifically for treating OCD or any mental health condition. Scientists continue to study its safety and effectiveness for these issues.

In earlier research, most people tolerated ketamine well, though some experienced side effects. Common side effects include dizziness or feeling disconnected from reality, which usually do not last long. Since this study is in an early stage, it primarily focuses on assessing ketamine's safety for people with OCD. Participants should be aware of these possible side effects and discuss any concerns with the study team or their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using ketamine for Obsessive-Compulsive Disorder (OCD) because it offers a new approach compared to traditional options like SSRIs and cognitive-behavioral therapy. Ketamine works rapidly, potentially providing relief in just hours or days, unlike other treatments that can take weeks. It targets the brain's glutamate system, offering a fresh mechanism of action compared to the serotonin-focused strategies of current treatments. Additionally, when combined with naltrexone, ketamine might offer enhanced benefits, addressing OCD symptoms in a novel way.

What evidence suggests that ketamine might be an effective treatment for OCD?

Research has shown that ketamine can quickly reduce symptoms of OCD (Obsessive-Compulsive Disorder). One study reported a 49.7% decrease in OCD symptoms within the first hour of ketamine use. Another study found that ketamine led to rapid and lasting improvements in OCD symptoms compared to other treatments, with some patients experiencing complete or partial symptom reduction. This trial will test ketamine in combination with either naltrexone or a placebo to further evaluate its potential as a promising treatment for OCD. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Obsessive-Compulsive Disorder (OCD) who haven't improved after trying at least one standard treatment. Participants must agree to fast before sessions, not join other trials during this study, and commit to the medication procedures.

Inclusion Criteria

I agree to fast before sessions, not join other trials, and follow medication procedures.

I have tried at least one standard OCD treatment without success.

Meet the criteria for OCD diagnosis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single infusion of 0.5mg/kg of ketamine with either naltrexone or placebo, with fMRI scans before, during, and after infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in OCD symptoms using the YBOCS scale

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Naltrexone Pill
• Placebo pill

Trial Overview The study tests how ketamine affects OCD symptoms compared to a placebo. It also examines if blocking opioid receptors with naltrexone changes ketamine's effects. Patients are randomly given either ketamine or placebo, and some will receive naltrexone.

How Is the Trial Designed?

Group I: Ketamine + Naltrexone Experimental Treatment 2 Interventions

OCD patients in this arm will receive 0.5mg/kg of ketamine - one single infusion. fMRI will be acquired before, during, and after infusion. Oral naltrexone 50 mg will be administered before the infusion.

Group II: Healthy Volunteers Active Control 1 Intervention

Healthy volunteers will have one fMRI scan visit.

Group III: Ketamine + Placebo Placebo Group 2 Interventions

OCD patients in this arm will receive 0.5mg/kg of ketamine - one single infusion. fMRI will be acquired before, during, and after infusion. An oral inactive placebo will be administered before the infusion.

Ketamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

S-ketamine significantly reduces compulsive behavior in the marble-burying test, suggesting its potential anti-compulsive effects in OCD, without affecting general locomotor activity.

The anti-compulsive effect of S-ketamine is linked to the activation of AMPA receptors and involves the ventromedial orbitofrontal cortex (vmOFC), indicating a specific mechanism of action distinct from its antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S-ketamine reduces marble burying behaviour: Involvement of ventromedial orbitofrontal cortex and AMPA receptors. Tosta, CL., Silote, GP., Fracalossi, MP., et al.[2019]

Oral S-ketamine was successfully used as a maintenance treatment for a patient with severe depression who did not respond to electroconvulsive therapy and deep brain stimulation, highlighting its potential efficacy in treatment-resistant cases.

The patient also had comorbid psychotic and obsessive-compulsive symptoms, suggesting that S-ketamine may be beneficial for individuals with complex mental health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral S-ketamine effective after deep brain stimulation in severe treatment-resistant depression and extensive comorbidities. Veraart, JKE., Kamphuis, J., Schlegel, M., et al.[2021]

Ketamine, while effective as a rapid antidepressant in treatment-resistant depression, showed no sustained benefits for obsessive-compulsive disorder (OCD) in a small trial of 10 subjects, with only some experiencing acute antidepressant effects.

Concerns arose regarding delayed-onset dysphoria and increased anxiety or suicidal thoughts in patients with OCD and other psychiatric issues, highlighting the need for caution and further research before using ketamine off-label in such cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two cases of delayed-onset suicidal ideation, dysphoria and anxiety after ketamine infusion in patients with obsessive-compulsive disorder and a history of major depressive disorder. Niciu, MJ., Grunschel, BD., Corlett, PR., et al.[2022]

Oral ketamine has shown effectiveness in treating severe depression, including treatment-resistant cases and those with suicidal ideation, based on various studies including randomized controlled trials with doses ranging from 0.25 to 7 mg/kg.

Despite its lower bioavailability (20%-25% reaching the bloodstream), oral ketamine is well tolerated and can be adjusted for individual needs, making it a practical option for depression treatment alongside conventional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. Andrade, C.[2019]

Ketamine and esketamine show promise in treating disorders within the obsessive-compulsive spectrum, such as OCD, eating disorders (ED), and substance use disorders (SUD), due to their effects on glutamatergic neurotransmission, which is dysregulated in these conditions.

Despite encouraging results from numerous small studies, there is still a lack of solid evidence supporting the long-term efficacy and safety of ketamine and esketamine for these disorders, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potentials of Ketamine and Esketamine in Obsessive-Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature. Martinotti, G., Chiappini, S., Pettorruso, M., et al.[2021]

In a 10-week clinical trial with 34 children and adolescents, N-Acetylcysteine (NAC) significantly improved symptoms of obsessive-compulsive disorder (OCD) when used alongside the SSRI citalopram, as indicated by a notable decrease in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores.

NAC was well tolerated with no serious adverse effects reported, suggesting it is a safe adjuvant treatment for enhancing the efficacy of SSRIs in managing OCD in young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of N-Acetylcysteine Augmentation on Obsessive Compulsive Disorder: A Multicenter Randomized Double Blind Placebo Controlled Clinical Trial. Ghanizadeh, A., Mohammadi, MR., Bahraini, S., et al.[2020]

In a trial involving 10 subjects with treatment-refractory OCD, ketamine infusion did not lead to significant improvements in OCD symptoms within the first 3 days, with less than 12% reduction observed.

However, 4 out of 7 patients with comorbid depression did show a rapid antidepressant response, indicating that while ketamine may help with depression, its effects on OCD symptoms were minimal and did not persist after the initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ketamine in treatment-refractory obsessive-compulsive disorder. Bloch, MH., Wasylink, S., Landeros-Weisenberger, A., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35267254/

Ketamine in the Treatment of Obsessive-Compulsive ... Reported data have shown a potential for fast onset of action and good tolerability of ketamine for OCD, even though the principal studies used only single- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05577585

Study Details | NCT05577585 | Ketamine in OCD: Efficacy ... There will be a change of severity of obsessive and compulsive symptoms seven days after ketamine infusion compared to midazolam infusion as measured with the ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1876201820302951

Clinical utility of repeated intravenous ketamine treatment ... One patient showed a dramatic response (a drop in the YBOCS to '0') and two patients showed a partial response (25–35 % reduction in the YBOCS). Eleven patients ...

4. jnnp.bmj.com jnnp.bmj.com/content/92/8/A10.1

reviewing effects of ketamine in OCD Combined, OCD scores decline by approximately 49.7% during the first hour following intravenous ketamine administration.

5. biologicalpsychiatryjournal.com biologicalpsychiatryjournal.com/article/S0006-3223(23)00292-5/fulltext

35. Efficacy of Ketamine in Unmedicated Adults With OCD Ketamine demonstrated rapid and durable OCD symptom improvement compared to the active control condition. By using an optimized active placebo design to control ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11760645/

Ketamine for treatment-resistant obsessive-compulsive disorder Blinded safety data were reviewed during the study by an independent Data Safety Monitoring Board and this resulted in the change in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01100255

Pilot Study of Ketamine in Adults With Obsessive ... In this study investigators are studying the effects of a drug called ketamine on the symptoms of Obsessive-compulsive disorder (OCD).

8. fda.gov fda.gov/drugs/human-drug-compounding/fda-warns-patients-and-health-care-providers-about-potential-risks-associated-compounded-ketamine

FDA warns about compounded ketamine for psychiatric ... Ketamine is not FDA approved for the treatment of any psychiatric disorder, and additional clinical studies are needed to adequately investigate ...

9. med.stanford.edu med.stanford.edu/stanmed/2017summer/carolyn-rodriguez-ketamine-OCD

The pros and cons of ketamine - Stanford Medicine In those patients who were given ketamine, the effect was immediate. Patients reported dramatic decreases in their obsessive-compulsive symptoms midway through ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8794478/

Ketamine Augmentation of Exposure Response Prevention ... Differentiating between obsessions and delusions can be difficult; thus, ketamine protocols should be used with caution in cases of OCD with psychotic features.