Glucose Consumption During Deep Brain Stimulation With Functional [18F]FDG-Brain-PET in Obsessive-Compulsive Disorder

Study Overview
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Brief Summary
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The purpose of this randomized, sham-controlled study is to evaluate the effectiveness of DBS therapy in individuals suffering from severe OCD and to investigate DBS treatment with functional [18F]FDG-Brain-PET.

Detailed Description
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The overall planned study duration per subject is 36 weeks, whereby inclusion is timepoint zero and implantation of DBS will be conducted during the first four study weeks. Patients will then undergo an 8-week open-label active DBS treatment phase followed by a 12-week double blind active or sham treatment and finally a 12-week crossover period with the inverse (active/sham) treatment with at least biweekly study visits. Patients as well as patient handling study psychiatrists will be blinded to active/sham. In case of unbearable aggravation of the symptoms during sham, the sham-period will be shortened to a tolerable length. After maximal 38 weeks all study procedures will be completed, and active DBS treatment will be maintained as long as clinically necessary.

Official Title
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Glucose Consumption During Deep Brain Stimulation With Functional [18F]FDG-Brain-PET in Obsessive-Compulsive Disorder

Conditions
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Obsessive-Compulsive Disorder, Psychiatric Disorder

Intervention / Treatment
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* Device: Implantation of a DBS therapy system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a score of 25 or higher on the Yale-Brown Obsessive Compulsive Scale previous failure to respond to at least two medication trials with serotonin reuptake inhibitors at or, if tolerated, beyond the FDA maximum recommended dose for a minimum duration over at least ten weeks each. at least one trial with tricyclic medication at or, if tolerated, beyond the FDA maximum recommended dose for a minimum duration over at least ten weeks each. at least one trial of augmentation with antipsychotic medication, lithium, a benzodiazepine or buspirone at least on trial of psychotherapy (cognitive behavioral therapy or comparable techniques) for at least 20 sessions ability to provide written informed consent Exclusion Criteria: any history of current or past psychotic disorder a manic episode within the preceding three years any current clinically significant medical or neurological disorder, that is a contraindication against DBS any disease that could lead to an altered glucose reactivity (e.g. diabetes) any clinically significant preoperative MRI abnormality or inability to undergo presurgical MRI current or unstable remitted substance abuse or dependence except nicotine pregnancy or high risk of becoming pregnant during study duration (desire to have children) and refusal to utilize a proper method of contraception Any current severe personality disorder except comorbid anankastic personality disorder Inability to follow the study protocol or adhere to operational requirements Current and unstable suicidality

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: After 8 weeks of open label DBS optimization and treatment, randomization to 12 weeks active or 12 weeks sham DBS treatment followed by a crossover switch at study week 24 to the opposing condition.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Subjects in this arm will receive active stimulation.<br>The Medtronic DBS system will be implanted in subjects in both study arms. Stimulation will vary depending on the study arm assignment. All subjects will receive therapeutic settings at the end of the blinded period. | Device: Implantation of a DBS therapy system<br>* The system is called Reclaim DBS Therapy for OCD und is marketed by Medtronic (Minneapolis, Minnesota). It has a HDE status by the FDA. The system consists of two quadripolar electrodes (Medtronic Reclaim DBS) as well as a generator (Medtronic Activa PC), which will be implanted into a subcutaneous pocket below the clavicula.<br>|
| Sham Comparator: Subjects in this arm will receive sham stimulation with DBS being turned off.<br>The Medtronic DBS system will be implanted in subjects in both study arms. Stimulation will vary depending on the study arm assignment. All subjects will receive therapeutic settings at the end of the blinded period. | Device: Implantation of a DBS therapy system<br>* The system is called Reclaim DBS Therapy for OCD und is marketed by Medtronic (Minneapolis, Minnesota). It has a HDE status by the FDA. The system consists of two quadripolar electrodes (Medtronic Reclaim DBS) as well as a generator (Medtronic Activa PC), which will be implanted into a subcutaneous pocket below the clavicula.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of metabolic rates of glucose response pattern | Change of metabolic rates of glucose response pattern | fPET measurements will take place in Week 4 and Week 5 of the trial. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of association between metabolic (change in glucose consumption - PET), structural (white matter pathways - DTI) and functional connectivity (resting state fMRI - functional connectivity patterns) | Combination of [18F]FDG-PET data with DTI and resting state fMRI data | Data acquisition will take place during screening and in the first 5 weeks of the study. | 
| Change in YBOCS scores by active DBS treatment and sham treatment | Comparison of YBOCS scores during active and sham treatment | Week 1 to 38 | 
| Correlation of metabolic (change in glucose consumption) and connectivity measures (white matter pathways) with clinical outcomes (YBOCS) and neuropsychological tests (SSRT, n-back, WCST) | YBOCS will serve as a marker for clinical outcome | Data acquisition will take place during screening and in Week 1 to Week 38 of the study. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FDG-PET, Deep Brain Stimulation, Brain Glucose Consumption