Obsessive Compulsive Disorder
Conditions
Brief summary
The purpose of this study is to test the efficacy of 1-Hz repetitive transcranial magnetic stimulation (TMS) over the pre-supplementary motor area as a treatment for obsessive compulsive disorder. Additionally, this study aims to identify the mechanisms of action of TMS and potential biomarkers and predictors of treatment response.
Detailed description
This treatment study examines the use of transcranial magnetic stimulation (TMS) in treating people with OCD and investigates what areas of the brain are involved during emotional learning. TMS is a noninvasive method in which a magnetic "coil" is placed near an individual's head and delivers small magnetic pulses into the brain, which produce small electrical currents in the brain, stimulating brain cells that may relieve OCD symptoms. TMS has been FDA approved since 2008 and Health Canada approved since 2002 as a treatment for depression. Our hope is to demonstrate that TMS is a successful treatment option for individuals struggling with OCD symptoms, and to identify the specific areas of the brain that are targeted through TMS. Patients will be randomized (like the flip of a coin) to one of two groups: 6 weeks of daily active TMS, or 6 weeks of daily placebo (sham) TMS sessions. During phase I, participation in this study will last about 8 weeks and patients will be asked to make about 36 visits to our clinics at the MGH main campus and the MGH Charlestown Navy Yard campus. Patients will also participate in MRI scanning sessions and clinical assessments. If patients' symptoms do not improve after phase I, they will be invited to participate in phase II. During phase II, patients receive 30 active TMS sessions over 6 weeks, as well as MRI scans and clinical assessments. Part of the MRI scanning sessions will include participating in a task that uses mild, half-second electric shocks to fingers. The electric current will be generated from a 9V battery (e.g., battery in a smoke alarm), and is much less annoying than a static shock. In order to set the level of the current to be used during the study, we will begin at a level below what patients will be able to feel, and then increase in gradual steps with permission. Patients will be asked to stop the increase at a level of the current that they find highly annoying but not painful. The level of current that patients select during this trial procedure, and no higher level, will be used during the study so that they will not receive any painful electric shocks. The purpose of the electric shock is to create a situation in which emotional learning may occur. Patients will receive no more than ten of these electric shocks. Compensation is provided for clinical assessments and MRI scan sessions.
Interventions
DEVICETranscranial Magnetic Stimulation
Transcranial magnetic stimulation uses a rapidly changing magnetic field to induce current in brain tissue non-invasively. It is common procedure in both clinical and research settings, and it has well established guidelines for safe an ethical use which maximize safety for all subjects.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. 18-65 years of age. 2. Proficient in English. 3. A diagnosis of primary OCD (as determined by SCID). 4. Yale-Brown Obsessive Compulsive Scale total score ≥ 16. 5. Normal (or corrected) vision. 6. Stable medication regimen or medication free for ≥ 12 weeks prior to study; benzodiazepine free ≥ 2 weeks. 7. Right-handed (Edinburgh Handedness Inventory - Short Form total score ≥ 61) 8. Able to give informed consent.
Exclusion criteria
1. Current or history of neurologic or psychiatric disease (e.g., mental retardation, dementia, brain damage, or other cognitive impairment) that would interfere with ability to engage in TMS 2. Psychopathology not appropriate for the treatment (e.g., manic episode or psychosis) 3. Substance abuse or dependence that is current or within the last six months or use of an illicit drug that is not prescribed, as indicated by a urine drug screen and/or clinical inference. 4. Use of benzodiazepines or anticonvulsants within 2 weeks prior to study (to be ruled out by a urine drug screen). 5. Use of Tricyclic Antidepressants (e.g. Clomipramine). 6. Use of other psychotropic medications (e.g., SSRIs) will be allowed provided the dose has been stable for \> 12 weeks. 7. Documented resistance to 4 or more valid pharmacological trials of 2 or more different medication classes (e.g. SSRIs and TCAs). 8. Previous exposure to TMS. 9. Major/chronic medical conditions. 10. History of head injury resulting in prolonged loss of consciousness and/or neurological sequelae. 11. Prior neurosurgical procedure. 12. Metal in the body, metal injury to the eyes. 13. History of seizures. 14. Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, or ventriculo-peritoneal shunt 15. Pregnancy; breastfeeding or nursing; for women of childbearing a pregnancy test (to be ruled out by urine β-HCG) will be conducted prior to study. 16. Currently in Cognitive Behavioral Therapy (CBT). 17. Diagnosis of primary sleep disorder such as primary insomnia, narcolepsy, sleep apnea, shift work sleep disorder and others. Sleep disorders such as insomnia or hypersomnia that are secondary to depression or OCD are permitted.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Obsessive Compulsive Symptoms as Measured by Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | Change in YBOCS from baseline (week 0) to post-treatment (week 6), assessed every 2 weeks. Followup phase data was measured at week 18. | The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is the gold-standard, semi-structured clinician-administered assessment of OCD symptom severity. It contains 10 items ranging from 0 (no symptoms) to 4 (extreme symptoms), yielding a total possible score range from 0 to 40. Higher scores indicate more severe OCD symptom severity. We compared the efficacy of TMS to Sham in reducing OCD symptom severity over a 6-week period. Efficacy was again compared in the follow-up phase of the study in from week 6 to week 18. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Obsessive Compulsive Beliefs as Measured by Obsessive-Compulsive Beliefs Questionnaire (OBQ) | Change in OBQ from baseline (week 0) to post-treatment (week 6), assessed every 2 weeks. Followup phase data was measured at week 18. | The Obsessive-Compulsive Beliefs Questionnaire (OBQ) is a patient-rated assessment of beliefs considered important in the development and maintenance of obsessive-compulsive disorder (OCD). It contains 44 items ranging from 1 (disagree very much) to 7 (agree very much) across 3-4 thought domains, yielding a total possible score range from 44 to 308. Higher scores indicate more strongly held OCD-related beliefs. We compared the efficacy of TMS to Sham in reducing OCD beliefs over a 6-week period. Efficacy was again compared in the follow-up phase of the study in from week 6 to week 18. |
| Total Number of Obsessive Symptoms is Reduced as Measured by Obsessive-Compulsive Inventory Questionnaire (OCI)-Revised | Change in OCI from baseline (week 0) to post-treatment (week 6), assessed every 2 weeks. Followup phase data was measured at week 18. | The Obsessive Compulsive Inventory-Revised (OCI-R) is a self-report questionnaire that measures OCD symptoms across 6 sub-scales including washing, checking, neutralizing, obsessing, ordering and hoarding. It contains 18 items ranging from 0 (not at all) to 4 (extremely), yielding a total possible score range from 0 to 72. Higher scores indicate more severe OCD symptoms. We compared the efficacy of TMS to Sham in reducing inventory of obsessive symptoms over a 6-week period. Efficacy was again compared in the follow-up phase of the study in from week 6 to week 18. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJoan A Camprodon, MD, MPH, PhD
Massachusetts General Hospital
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Transcranial Magnetic Stimulation (TMS) Treatment In this arm subjects will receive real, active TMS with a standard, water-cooled, figure-8 shaped TMS coil.
Transcranial Magnetic Stimulation: Transcranial magnetic stimulation uses a rapidly changing magnetic field to induce current in brain tissue non-invasively. It is common procedure in both clinical and research settings, and it has well established guidelines for safe an ethical use which maximize safety for all subjects. See attached Rossi et. al. 2009 as a reference to safety guidelines for TMS. | 15 |
| Sham-TMS Treatment This arm serves as the sham/placebo control. In TMS a sham coil is used to create a sensory experience which is similar to active TMS, but in which the magnetic field is blocked by a metal shield built into the coil.
Transcranial Magnetic Stimulation: Transcranial magnetic stimulation uses a rapidly changing magnetic field to induce current in brain tissue non-invasively. It is common procedure in both clinical and research settings, and it has well established guidelines for safe an ethical use which maximize safety for all subjects. See attached Rossi et. al. 2009 as a reference to safety guidelines for TMS. | 11 |
| Total | 26 |
Baseline characteristics
| Characteristic | Active Transcranial Magnetic Stimulation (TMS) Treatment | Sham-TMS Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 11 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 7 Participants | 20 Participants |
| Region of Enrollment United States | 15 participants | 11 participants | 26 participants |
| Sex: Female, Male Female | 9 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 11 | 0 / 16 |
| other Total, other adverse events | 6 / 15 | 1 / 11 | 3 / 16 |
| serious Total, serious adverse events | 0 / 15 | 0 / 11 | 0 / 16 |
Outcome results
Primary
Obsessive Compulsive Symptoms as Measured by Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is the gold-standard, semi-structured clinician-administered assessment of OCD symptom severity. It contains 10 items ranging from 0 (no symptoms) to 4 (extreme symptoms), yielding a total possible score range from 0 to 40. Higher scores indicate more severe OCD symptom severity. We compared the efficacy of TMS to Sham in reducing OCD symptom severity over a 6-week period. Efficacy was again compared in the follow-up phase of the study in from week 6 to week 18.
Time frame: Change in YBOCS from baseline (week 0) to post-treatment (week 6), assessed every 2 weeks. Followup phase data was measured at week 18.
Population: Number Analyzed in Row Differs Due to Missing/Incomplete Data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Transcranial Magnetic Stimulation (TMS) Treatment | Obsessive Compulsive Symptoms as Measured by Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | Week 0 | 23.9 score on a scale | Standard Deviation 4.2 |
| Active Transcranial Magnetic Stimulation (TMS) Treatment | Obsessive Compulsive Symptoms as Measured by Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | Week 6 | 23.23 score on a scale | Standard Deviation 4.4 |
| Active Transcranial Magnetic Stimulation (TMS) Treatment | Obsessive Compulsive Symptoms as Measured by Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | Week 18 | 23.5 score on a scale | Standard Deviation 3.5 |
| Sham-TMS Treatment | Obsessive Compulsive Symptoms as Measured by Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | Week 0 | 23.1 score on a scale | Standard Deviation 4.1 |
| Sham-TMS Treatment | Obsessive Compulsive Symptoms as Measured by Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | Week 6 | 20.6 score on a scale | Standard Deviation 5.5 |
| Sham-TMS Treatment | Obsessive Compulsive Symptoms as Measured by Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | Week 18 | 17.0 score on a scale | Standard Deviation 8.2 |
Secondary
Obsessive Compulsive Beliefs as Measured by Obsessive-Compulsive Beliefs Questionnaire (OBQ)
The Obsessive-Compulsive Beliefs Questionnaire (OBQ) is a patient-rated assessment of beliefs considered important in the development and maintenance of obsessive-compulsive disorder (OCD). It contains 44 items ranging from 1 (disagree very much) to 7 (agree very much) across 3-4 thought domains, yielding a total possible score range from 44 to 308. Higher scores indicate more strongly held OCD-related beliefs. We compared the efficacy of TMS to Sham in reducing OCD beliefs over a 6-week period. Efficacy was again compared in the follow-up phase of the study in from week 6 to week 18.
Time frame: Change in OBQ from baseline (week 0) to post-treatment (week 6), assessed every 2 weeks. Followup phase data was measured at week 18.
Population: Number Analyzed in Row Differs Due to Missing/Incomplete Data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Transcranial Magnetic Stimulation (TMS) Treatment | Obsessive Compulsive Beliefs as Measured by Obsessive-Compulsive Beliefs Questionnaire (OBQ) | Week 0 | 186.53 score on a scale | Standard Deviation 53.29 |
| Active Transcranial Magnetic Stimulation (TMS) Treatment | Obsessive Compulsive Beliefs as Measured by Obsessive-Compulsive Beliefs Questionnaire (OBQ) | Week 6 | 190.60 score on a scale | Standard Deviation 63.55 |
| Active Transcranial Magnetic Stimulation (TMS) Treatment | Obsessive Compulsive Beliefs as Measured by Obsessive-Compulsive Beliefs Questionnaire (OBQ) | Week 18 | 220.00 score on a scale | Standard Deviation 73.54 |
| Sham-TMS Treatment | Obsessive Compulsive Beliefs as Measured by Obsessive-Compulsive Beliefs Questionnaire (OBQ) | Week 0 | 178.91 score on a scale | Standard Deviation 33.15 |
| Sham-TMS Treatment | Obsessive Compulsive Beliefs as Measured by Obsessive-Compulsive Beliefs Questionnaire (OBQ) | Week 6 | 180.30 score on a scale | Standard Deviation 36.9 |
| Sham-TMS Treatment | Obsessive Compulsive Beliefs as Measured by Obsessive-Compulsive Beliefs Questionnaire (OBQ) | Week 18 | 147.00 score on a scale | Standard Deviation 89.1 |
Secondary
Total Number of Obsessive Symptoms is Reduced as Measured by Obsessive-Compulsive Inventory Questionnaire (OCI)-Revised
The Obsessive Compulsive Inventory-Revised (OCI-R) is a self-report questionnaire that measures OCD symptoms across 6 sub-scales including washing, checking, neutralizing, obsessing, ordering and hoarding. It contains 18 items ranging from 0 (not at all) to 4 (extremely), yielding a total possible score range from 0 to 72. Higher scores indicate more severe OCD symptoms. We compared the efficacy of TMS to Sham in reducing inventory of obsessive symptoms over a 6-week period. Efficacy was again compared in the follow-up phase of the study in from week 6 to week 18.
Time frame: Change in OCI from baseline (week 0) to post-treatment (week 6), assessed every 2 weeks. Followup phase data was measured at week 18.
Population: Number Analyzed in Row Differs Due to Missing/Incomplete Data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Transcranial Magnetic Stimulation (TMS) Treatment | Total Number of Obsessive Symptoms is Reduced as Measured by Obsessive-Compulsive Inventory Questionnaire (OCI)-Revised | Week 0 | 26.27 score on a scale | Standard Deviation 11.21 |
| Active Transcranial Magnetic Stimulation (TMS) Treatment | Total Number of Obsessive Symptoms is Reduced as Measured by Obsessive-Compulsive Inventory Questionnaire (OCI)-Revised | Week 6 | 31.00 score on a scale | Standard Deviation 12.32 |
| Active Transcranial Magnetic Stimulation (TMS) Treatment | Total Number of Obsessive Symptoms is Reduced as Measured by Obsessive-Compulsive Inventory Questionnaire (OCI)-Revised | Week 18 | 30.50 score on a scale | Standard Deviation 10.61 |
| Sham-TMS Treatment | Total Number of Obsessive Symptoms is Reduced as Measured by Obsessive-Compulsive Inventory Questionnaire (OCI)-Revised | Week 0 | 31.20 score on a scale | Standard Deviation 14.05 |
| Sham-TMS Treatment | Total Number of Obsessive Symptoms is Reduced as Measured by Obsessive-Compulsive Inventory Questionnaire (OCI)-Revised | Week 6 | 24.70 score on a scale | Standard Deviation 11.4 |
| Sham-TMS Treatment | Total Number of Obsessive Symptoms is Reduced as Measured by Obsessive-Compulsive Inventory Questionnaire (OCI)-Revised | Week 18 | 15.50 score on a scale | Standard Deviation 19.09 |