Development of Adaptive Deep Brain Stimulation for OCD
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|ClinicalTrials.gov Identifier: NCT03457675|
Recruitment Status : Recruiting
First Posted : March 7, 2018
Last Update Posted : January 17, 2019
|First Submitted Date ICMJE||August 14, 2017|
|First Posted Date ICMJE||March 7, 2018|
|Last Update Posted Date||January 17, 2019|
|Actual Study Start Date ICMJE||July 11, 2018|
|Estimated Primary Completion Date||June 2022 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT03457675 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Rating OCD Symptom Severity [ Time Frame: Baseline to 30 days ]
measured after closed-loop stimulation
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Development of Adaptive Deep Brain Stimulation for OCD|
|Official Title ICMJE||Development of Adaptive Deep Brain Stimulation (aDBS) for the Treatment of Intractable OCD: Phase Ia Using Activa PC+S|
This research study is for participants that have been diagnosed with intractable Obsessive -compulsive disorder (OCD). OCD is a persistent and oftentimes disabling disorder marked by unwanted and distressing thoughts (obsessions) and irresistible repetitive behaviors. OCD affects 2-3% of the US population, and is responsible for substantial functional impairment and increased risk of early death.
The only established first-line treatments for OCD are cognitive-behavioral therapy (CBT) with exposure/response prevention and certain medications. About 30-40% of patients fail to respond and few experience complete symptom resolution. Up to 25% of patients have difficulty tolerating CBT and the risk of relapse after therapies remains large. For the most severe cases, neurosurgery (surgery in the brain), has long been the option of last resort.
In this study the investigators want develop an adaptive Deep Brain Stimulation (aDBS) system to use in subjects with intractable (hard to control) OCD. Deep brain stimulation remains investigational for OCD patients and is not considered standard therapy. DBS involves the surgical implantation of leads and electrodes into specific areas of the brain, which are thought to influence the disease. A pack implanted in the chest, called the neurotransmitter, keeps the electrical current coursing to the brain through a wire that connects the neurotransmitter and electrodes. It is believed deep brain stimulation may restore balance to dysfunctional brain circuitry implicated in OCD. The goal of this study is to enhance current approaches to DBS targeting in the brain and to use a novel approach to find a better and more reliable system for OCD treatment.
Phase Ia is to gather data to eventually develop a prototype adaptive DBS system for intractable OCD that uses signals from the brain to automatically adjust the DBS stimulation factors. The overall goal is to improve symptom management and reduce stimulation-induced behavioral side effects.
Potential participants will be referred to our program by their treating clinicians, who will be made aware of our study through direct clinician-clinician letters and emails. Subjects may also learn of the study through consumer advocacy groups such as the International OCD Foundation (IOCDF), local non-profit organizations and local support group meetings and through the normals avenues that they share information.
A subject is considered enrolled upon signing informed consent, deemed eligible to be screened by the investigator. Decision-making capacity, which includes understanding, appreciation, reasoning and ability to express a choice, will be assessed as part of the informed consent process. The informed consent process will include discussions with the patient's family and referring clinician. Medical records will be carefully reviewed to determine adequacy of past treatments including CBT.
Potential subjects meeting inclusion/exclusion criteria and willing to participate in the study as demonstrated by signing the informed consent will be enrolled in the study and undergo screening.
After the participant signs the required documents, he/she will undergo two baseline evaluations spaced over an approximate 1 month period. Diagnostic and screening ratings are completed, followed by complete medical, neurological and neurosurgical evaluations. The raters will be trained and certified in the use of the clinician-administered scales of the study. The purpose of the screening evaluations is to demonstrate that subject is in a stable clinical situation including a stable medical regimen, and are severely symptomatic. If this is the case, and they continue to meet inclusion/exclusion criteria, the participant will proceed to treatment (surgery to implant the DBS system. Final selection of candidates will be made by consensus of the multi-disciplinary investigator team ("Project Advisory Committee").
Subjects treated in Phase 1a will undergo a single stage DBS surgery, in which bilateral deep brain leads will be implanted under conscious sedation, followed by implantation of a single Implantable NeuroStimulator (INS), Activa PC+S, under general anesthesia.
The subject will return to clinic about 2 weeks post-surgery for their post-surgical psychiatric symptom baseline and recording visit (Visit 5). Programming of the DBS device will occur at Visit 6, 1 week later.
The subject will return to clinic every 2 weeks for the first 2 months following the system activation. Each visit will last about 3-4 hours and will include clinician administered assessments, self-rated assessments, recordings and tasks to be performed.
Post-surgical 1.5 rs-fMRI scans will also be performed according to Medtronic standard post-implant MRI guidelines for deep brain stimulation systems to ensure safety.
Participants will be asked to keep their current medications constant for the first 6 months post-surgery. However, clinical circumstances which mandate changes will be allowed and notated should this occur.
The Provocation OC task (Provoc) and the Trier Social Stress Test (TSST) will be used to start OC-related distress and distress unrelated to OCD (e.g., performance anxiety), respectively. Three sessions will be videotaped with Automated Facial Affect Recognition (AFAR) system concurrent to recording of local field potentials (LFPs) from VS and scalp electroencephalography (EEG).
Starting at Month 7, subjects will receive a two-month (15 session) cognitive behavioral therapy (CBT) course where exposure and response prevention (ERP) for OCD will be delivered. Subjects already receiving stable CBT will be allowed to continue it during the study. Instead, we have developed standardized instructions to encourage exposure and resist compulsions (ERP) during this portion of the trial. Participants will be encouraged at study visits to actively confront OC triggers while refraining from ritual engagement. Subjects, especially those who are still habitually avoiding, will be given the opportunity to derive maximal clinical benefit by receiving a two-month "refresher" course of CBT prior to entering the double-blind discontinuation phase at 9 months.
Double Blinded Discontinuation:
The purpose of the one-month blinded discontinuation period is to confirm clinical benefit. At the end of month 8, subjects will enter a one-month delayed onset withdrawal period in which the subject and Independent Evaluators are blinded to timing of discontinuation. The decision whether to reinstate active DBS at the end of the discontinuation will be based on clinical considerations in discussion with the subject and significant others. The benefits and discomforts will be carefully weighed in arriving at a long-term plan. Escape criteria will include withdrawing consent or significant clinical deterioration warranting unblinding or reinstatement of treatment. Following exit from the discontinuation period, treatment will recommence as clinically indicated, including stimulation resumption or continued observation with the device off.
Monthly Programming/Classification/Evaluation Visits until End of Study (EOS):
Months 10-18 (Visits 20-28) - Following exit from the discontinuation phase based on clinical indication, treatment will recommence as clinically indicated around Month 10, including stimulation resumption or continued observation with device off. Refining state classifications and testing machine learning will continue, if stimulation is reinstated. Subjects that participated in the discontinuation phase will be considered off-treatment once Month 18 visit (Visit 298) has occurred.These visits will take place monthly for 9 months. Each visit will last approximately 3-4 hours.
After the 18 months of the study, the device will remain implanted in those subjects who are doing well clinically. For subjects who are not responsive, it will be explanted, if the surgical risks of explantation are deemed acceptable by the treatment team. The follow-up management will be arranged on a case-by-case basis, depending on geographic location and desires of the subject, and DBS therapy management by our team will be guaranteed for at least two years if subjects continue to receive DBS therapy and do not arrange alternative management during that period. Attempts will be made to collect all device-related adverse events in all willing participants at 6-month intervals after they exit the currently proposed study.
Subject participation is anticipated to continue for a minimum of 18 months.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Not Applicable|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
At the end of month 8 after DBS implant, all subjects will enter a one-month delayed onset withdrawal period in which the subject and Independent Evaluators are blinded to timing of discontinuation. See description below.Masking: Double (Participant, Outcomes Assessor)
In all cases, the sequence will be as follows in one-week segments: 100% Active, 50% Active, Sham and Sham. Subjects will be seen weekly. Amplitude will be reduced by 50% at start of week 2 and turned off at start of week 3. Subjects will be told that DBS will be discontinued at some point during the 4 weeks. The purpose of the 50% initial reduction is to minimize rebound effects. The programmer (not the PI in this case) will be open to the design and perform "sham" activation. Relapse is defined as a 25% increase of the Y-BOCS over two consecutive visits compared to discontinuation baseline.Primary Purpose: Treatment
|Condition ICMJE||Obsessive-Compulsive Disorder|
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||June 2023|
|Estimated Primary Completion Date||June 2022 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||21 Years to 70 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||Yes|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT03457675|
|Other Study ID Numbers ICMJE||H40255
1UH3NS100549 ( U.S. NIH Grant/Contract )
49340 ( Other Grant/Funding Number: BCM ID )
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||
|Responsible Party||Wayne Goodman MD, Baylor College of Medicine|
|Study Sponsor ICMJE||Baylor College of Medicine|
|PRS Account||Baylor College of Medicine|
|Verification Date||January 2019|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP