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

Not Applicable

Recruiting

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Subjects in this arm will receive active stimulation.	Implantation of a DBS therapy system	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.
Subjects in this arm will receive sham stimulation with DBS being turned off.	Implantation of a DBS therapy system	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.

Primary Outcome Measures

Name	Time	Method
Change of metabolic rates of glucose response pattern	fPET measurements will take place in Week 4 and Week 5 of the trial.	Change of metabolic rates of glucose response pattern

Secondary Outcome Measures

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

Locations (1): Medical University of Vienna, Department of Psychiatry and Psychotherapy
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Vienna, Austria