Obsessive-compulsive DisorderPhase 2NCT01349231
Ketamine Infusion for Obsessive-Compulsive Disorder
A Phase 2 study testing ketamine in people with Obsessive-compulsive Disorder, run by Yale University at 1 site in United States.
Trial summary
Roughly one-third of patients with obsessive-compulsive disorder (OCD) do not experience significant clinical benefit from first-line interventions such as pharmacotherapy with selective serotonin reuptake inhibitors (SSRI) or cognitive behavioral therapy (CBT). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Obsessive-compulsive Disorder
- What is being tested?
- ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Dec 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult between the ages of 18 and 65 years.
- Meet DSM IV criteria for obsessive-compulsive disorder by structured clinical interview (SCID) and have a Y-BOCS score >24.
- Have treatment-refractory OCD. Have Y-BOCS>24 despite two SSRI trials of adequate dose and duration and been offered prior CBT treatment.
- Stable psychiatric medications. Subjects must have had stable doses of all psychiatric medications for the month prior to treatment and have been on stable doses of SSRI and clomipramine for at least 2 months prior to study enrollment.
- Medically and neurologically healthy.
- Able to provide written informed consent according to the Yale HIC guidelines.
Who cannot join
- Lifetime history of substance dependence (other than nicotine and caffeine)
- Suicide attempt or suicidal ideation requiring psychiatric hospitalization in the previous 6 months
- Being Pregnant
- Known hypersensitivity to ketamine
Trial locations and contacts
1 site in 1 country.
United States1 site
Connecticut Mental Health Center/ YNHH
New Haven, Connecticut, 06520
About this study
Roughly one-third of patients with obsessive-compulsive disorder (OCD) do not experience significant clinical benefit from first-line interventions such as pharmacotherapy with selective serotonin reuptake inhibitors (SSRI) or cognitive behavioral therapy (CBT). Furthermore, OCD patients typically experience the full treatment benefits of first-line interventions only after a time-lag of two to three months. Inadequate symptom relief and delay of symptom relief from first-line treatments are sources of substantial morbidity and decreased quality of life in OCD patients. Converging lines of evidence from neuroimaging, genetic and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of OCD.
The investigators are conducting an open, uncontrolled study of ketamine in treatment-refractory OCD. Ketamine is a potent antagonist of the N-methyl-D-aspartate (NMDA) receptor and has been demonstrated to have rapid anti-depressant effects in patients with Major Depressive Disorder. The investigators have additionally provided evidence for rapid improvement of comorbid OCD and trichotillomania after ketamine infusion in a depressed woman.
Failure of symptom relief and delay of symptom relief from first-line treatments are a source of substantial morbidity and decreased quality of life in OCD patients. Ketamine represents the possibility to provide rapid symptom relief to OCD patients and may provide the mechanism for future drug development to treat OCD more rapidly and effectively.
Read the detailed description
Roughly one-third of patients with obsessive-compulsive disorder (OCD) fail to experience significant clinical benefit from first-line interventions such as pharmacotherapy with selective serotonin reuptake inhibitors (SSRI) or cognitive behavioral therapy (CBT). Antipsychotic augmentation is the only pharmacological strategy for treatment-refractory OCD with demonstrated efficacy in multiple double-blind trials (2). Antipsychotic augmentation only benefits around 1 in 3 treatment-refractory OCD. Furthermore, OCD patients typically experience the full treatment benefits of first-line interventions only after a time-lag of two to three months. Failure of symptom relief and delay of symptom relief from first-line treatments are sources of substantial morbidity and decreased quality of life in OCD patients.
Converging lines of evidence from neuroimaging, genetic and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of OCD. In Magnetic Resonance Spectroscopy studies elevated concentrations of glutamate and related compounds have been demonstrated in the caudate nucleus and orbitofrontal cortex of OCD patients compared to normal controls. In genetic studies, single nucleotide polymorphisms within the glutamate transporter gene SLC1A1 have been associated with the diagnosis of OCD. Open-label, pharmacological treatment studies have suggested that glutamate modulating agents such as riluzole, n-acetylcysteine and memantine may be effective in the treatment of OCD.
Ketamine is a potent antagonist of the N-methyl-D-aspartate (NMDA) receptor, a major type of glutamate receptor in the brain. In a placebo-controlled study completed at Yale a single dose of ketamine (0.5 mg/kg, intravenously) had rapid antidepressant effects in depressed patients. In these subjects ketamine infusion produced mild psychotomimetic symptoms and euphoria that dissipated within 120 minutes, while the antidepressant effects of ketamine infusion emerged over the first 180 minutes and persisted over 72 hours. Fifty percent of depressed patients receiving ketamine were treatment responders at Day 3 compared to 12.5% in the placebo infusion group. These results have been replicated in a recent double-blind study performed at NIMH and a third unpublished study conducted by members of our group at Yale.
Our goal is to conduct an open-label study in treatment-refractory OCD to determine if ketamine may be an effective acute anti-obsessional agent.
- Conditions
- Obsessive-compulsive Disorder
- Being tested
- ketamine
- Keywords
- obsessive-compulsive disorder, ketamine, glutamate
- Medical subject headings
- Obsessive-Compulsive Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ketamineDrug
Ketamine (a single 0.5mg intravenously over 40 minutes).
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Ketamine will be given at a dose of 0.5mg/kg over 40 minutes. This dose is identical to that used in previous anti-depressant studies of ketamine. Receives: Drug: ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
OCD Severity
We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 1 day following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.
Measured: Baseline and 1 day after ketamine infusion
OCD Severity
We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 2 days following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.
Measured: Baseline and 2 days following infusion
OCD Severity
We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 3 days following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.
Measured: Baseline and 3 days following infusion
Secondary outcomes (1)
Depression Symptoms
We will examine change from baseline in Hamilton Rating Scale for Depression (HRDS) ratings of depression severity at day 1-3 following a single ketamine infusion. The HRDS assesses severity of, and change in, depressive symptoms. The HRDS is a 21 item scale with scores ranging from 0-66. The higher the score, the more severe the depression.
Measured: Baseline, Day 1, Day 2, and Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2011 (estimated)
- Study startFeb 2009
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Obsessive-compulsive DisorderStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Responsible party
- Sponsor
- Investigators
- Michael H Bloch, MD, MS, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01349231
- Sponsor's protocol ID
- 0901004660
- Status last verified
- May 2014
- First submitted
- 9 Apr 2011
- Last updated
- 9 Jun 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Niciu MJ, Grunschel BD, Corlett PR, Pittenger C, Bloch MH. 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. J Psychopharmacol. 2013 Jul;27(7):651-4. doi: 10.1177/0269881113486718. Epub 2013 May 15.
PubMed 23676198
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketamine Infusion for Obsessive-Compulsive Disorder
- ClinicalTrials.gov ID
- NCT01349231
- Acronym / sponsor ID
- 0901004660
- Conditions
- Obsessive-compulsive Disorder
- Keywords
- obsessive-compulsive disorder, ketamine, glutamate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Study start
- Feb 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 6 May 2011 (estimated)
- Results
- Posted 9 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Roughly one-third of patients with obsessive-compulsive disorder (OCD) do not experience significant clinical benefit from first-line interventions such as pharmacotherapy with selective serotonin reuptake inhibitors (SSRI) or cognitive behavioral therapy (CBT). Furthermore, OCD patients typically experience the full treatment benefits of first-line interventions only after a time-lag of two to three months. Inadequate symptom relief and delay of symptom relief from first-line treatments are sources of substantial morbidity and decreased quality of life in OCD patients. Converging lines of evidence from neuroimaging, genetic and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of OCD.
The investigators are conducting an open, uncontrolled study of ketamine in treatment-refractory OCD. Ketamine is a potent antagonist of the N-methyl-D-aspartate (NMDA) receptor and has been demonstrated to have rapid anti-depressant effects in patients with Major Depressive Disorder. The investigators have additionally provided evidence for rapid improvement of comorbid OCD and trichotillomania after ketamine infusion in a depressed woman.
Failure of symptom relief and delay of symptom relief from first-line treatments are a source of substantial morbidity and decreased quality of life in OCD patients. Ketamine represents the possibility to provide rapid symptom relief to OCD patients and may provide the mechanism for future drug development to treat OCD more rapidly and effectively.
Detailed description
Roughly one-third of patients with obsessive-compulsive disorder (OCD) fail to experience significant clinical benefit from first-line interventions such as pharmacotherapy with selective serotonin reuptake inhibitors (SSRI) or cognitive behavioral therapy (CBT). Antipsychotic augmentation is the only pharmacological strategy for treatment-refractory OCD with demonstrated efficacy in multiple double-blind trials (2). Antipsychotic augmentation only benefits around 1 in 3 treatment-refractory OCD. Furthermore, OCD patients typically experience the full treatment benefits of first-line interventions only after a time-lag of two to three months. Failure of symptom relief and delay of symptom relief from first-line treatments are sources of substantial morbidity and decreased quality of life in OCD patients.
Converging lines of evidence from neuroimaging, genetic and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of OCD. In Magnetic Resonance Spectroscopy studies elevated concentrations of glutamate and related compounds have been demonstrated in the caudate nucleus and orbitofrontal cortex of OCD patients compared to normal controls. In genetic studies, single nucleotide polymorphisms within the glutamate transporter gene SLC1A1 have been associated with the diagnosis of OCD. Open-label, pharmacological treatment studies have suggested that glutamate modulating agents such as riluzole, n-acetylcysteine and memantine may be effective in the treatment of OCD.
Ketamine is a potent antagonist of the N-methyl-D-aspartate (NMDA) receptor, a major type of glutamate receptor in the brain. In a placebo-controlled study completed at Yale a single dose of ketamine (0.5 mg/kg, intravenously) had rapid antidepressant effects in depressed patients. In these subjects ketamine infusion produced mild psychotomimetic symptoms and euphoria that dissipated within 120 minutes, while the antidepressant effects of ketamine infusion emerged over the first 180 minutes and persisted over 72 hours. Fifty percent of depressed patients receiving ketamine were treatment responders at Day 3 compared to 12.5% in the placebo infusion group. These results have been replicated in a recent double-blind study performed at NIMH and a third unpublished study conducted by members of our group at Yale.
Our goal is to conduct an open-label study in treatment-refractory OCD to determine if ketamine may be an effective acute anti-obsessional agent.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: ketamineKetamine will be given at a dose of 0.5mg/kg over 40 minutes. This dose is identical to that used in previous anti-depressant studies of ketamine. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult between the ages of 18 and 65 years.
- Meet DSM IV criteria for obsessive-compulsive disorder by structured clinical interview (SCID) and have a Y-BOCS score >24.
- Have treatment-refractory OCD. Have Y-BOCS>24 despite two SSRI trials of adequate dose and duration and been offered prior CBT treatment.
- Stable psychiatric medications. Subjects must have had stable doses of all psychiatric medications for the month prior to treatment and have been on stable doses of SSRI and clomipramine for at least 2 months prior to study enrollment.
- Medically and neurologically healthy.
Key exclusion criteria (4 listed)
- Lifetime history of substance dependence (other than nicotine and caffeine)
- Suicide attempt or suicidal ideation requiring psychiatric hospitalization in the previous 6 months
- Being Pregnant
- Known hypersensitivity to ketamine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ketamineKetamine (a single 0.5mg intravenously over 40 minutes). | Drug | Ketamine |
Primary outcome
OCD Severity
Time frame: Baseline and 1 day after ketamine infusion
We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 1 day following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.
OCD Severity
Time frame: Baseline and 2 days following infusion
We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 2 days following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.
OCD Severity
Time frame: Baseline and 3 days following infusion
We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 3 days following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.
1 secondary outcome
Depression Symptoms
Time frame: Baseline, Day 1, Day 2, and Day 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23676198Niciu MJ, Grunschel BD, Corlett PR, Pittenger C, Bloch MH. 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. J Psychopharmacol. 2013 Jul;27(7):651-4. doi: 10.1177/0269881113486718. Epub 2013 May 15.
- Yale OCD Research ClinicLink provided by the sponsor.
Related trials for Obsessive-compulsive Disorder
Recruiting
Focused Ultrasound for Behavioral Health
Depression, Anxiety
Not yet recruiting
Linear Accelerator Radiosurgical Anterior Capsulotomy With Task-based fMRI Identification of PERSonalized and PrEdictiVE Biomarkers of REsponse in Treatment-Refractory Obsessive-Compulsive Disorder (PERSEVERE Trial)
Treatment-refractory Obsessive-compulsive Disorder (trOCD)
Recruiting
tDCS Associated With Symptom Provocation in the Management of Patients With Resistant Obsessive Compulsive Disorder
Obsessive-Compulsive Disorder
Recruiting
Mindfulness Intervention for Psychological and Family Dynamics in Children With Body-Focused Repetitive Behaviors
Mindfulness Skills, Psychosocial Education
RecruitingPhase 2
SONATA Dose Duration LIFU for OCD
Obsessive - Compulsive Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael H Bloch, MD, MS principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ketamine in people with Obsessive-compulsive Disorder, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
OCD Severity (time frame: Baseline and 1 day after ketamine infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01349231, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2014.