ARITEP: Serotonin Control of Impulsivity in Tourette Disorder
Study Details
Study Description
Brief Summary
Tourette disorder (TD) is a neurodevelopmental disorder characterized by motor and vocal tics. It is often associated with multiple psychiatric comorbidities involving a high degree of impulsivity such as obsessive-compulsive disorders (OCD), attention-deficit hyperactivity disorders (ADHD), and intermittent explosive disorders (IED). Although a substantial body of clinical studies have emphasized the role of the dopamine system in motor symptoms, little is known about how the serotonergic (5-HT) system modulate both cognitive and affective abilities in TD. Several lines of evidence suggest that different 5-HT receptor subtypes may constitute a crucial factor in the development and maintenance of different symptoms. Because abnormal 5-HT2A receptor bindings have been reported in patients with TD and aripiprazole (drug of first choice) is a 5-HT2A antagonist, we hypothesize that 5-HT2A receptors may play an important role in regulating psychiatric symptoms in TD such as those characterized by impulsive behaviors. To investigate the involvement of 5-HT2A receptors in TD, we propose to perform a multimodal imaging study with 20 adult patients (ON and OFF treatment). Neuroimaging data will be collected with a hybrid system that simultaneously combines the positron emission tomography (PET) and the functional magnetic resonance imaging (fMRI). A highly selective PET radiotracer ([18F]-altanserin) will map 5-HT2A receptor bindings in the whole brain, while fMRI will provide detail information regarding the altered brain activities.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Tourette disorder 20 mixt adult patients with TD. Patients will be recruited if a current treatment by aripiprazole (5-15 mg) is already scheduled before the study. |
Drug: Administration of a PET radiotracer
A highly selective 5-HT2A receptor ligand ([18F]-altanserin) will be injected to patients before each PET scan. The IV injection in the arm (via a catheter) will be performed in continue during a period of 2 hours in the imaging centre (CERMEP) before the acquisition. The dose will be 2,6 MBq/kg +/- 10 % depending the prescription of the nuclear medicine.
Patients will be evaluated twice, one time free of neuroleptic treatment and a second time during stable chronic treatment by neuroleptic.
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Outcome Measures
Primary Outcome Measures
- Correlation coefficients between receptor-specific imaging data (PET) and scores of impulsivity measured by the Barratt scale (BIS11). [As the analysis requires a complex imaging processing, this outcome measure will be assessed in the year following the acquisition.]
Correlation coefficients between changes in the binding potential (BPND) of [18F]-altanserin measured voxel-by-voxel in the whole brain and the evolution of scores BIS11 in TD patients.
Secondary Outcome Measures
- Correlation coefficients between receptor-specific imaging data (PET) and other clinical/behavioral scores. [As the analysis requires a complex imaging processing, this outcome measure will be assessed in the year following the acquisition.]
Correlation coefficients between changes in the binding potential (BPND) of [18F]-altanserin measured voxel-by-voxel in the whole brain and the evolution of other clinical scores and task performance of TD patients.
- Correlation coefficients between functional imaging data (fMRI) and scores of impulsivity measured by the Barratt scale (BIS11). [As the analysis requires a complex imaging processing, this outcome measure will be assessed in the year following the acquisition.]
Correlation coefficients between changes in the BOLD signal measured voxel-by-voxel in the whole brain and the evolution of scores BIS11 in TD patients.
- Correlation coefficients between functional imaging data (fMRI) and other clinical/behavioral scores. [As the analysis requires a complex imaging processing, this outcome measure will be assessed in the year following the acquisition.]
Correlation coefficients between changes in the BOLD signal measured voxel-by-voxel in the whole brain and the evolution of other clinical scores and task performance of TD patients.
Eligibility Criteria
Criteria
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Inclusion Criteria * :
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Male or Female
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Diagnosed with a Tourette Disorder following the DSM-5
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Age between 18-65 years
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Member of a social security scheme in France
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Freely-given informed consent to participate to this study (written form)
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With a current treatment by aripiprazole already scheduled
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With Tics compatible with TEP/fMRI exams
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Having (for women only) effective contraception throughout participation in the study.
Exclusion Criteria * :
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Male or Female
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A serious not controlled psychiatric comorbidity
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A serious, evolving or debilitating pathology with a potential influence on the study
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Drug-taking with serotonergic effects (e.g., amphetamine, cocaine, MDMA, SSRIs, mianserin)
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Contraindication for fMRI and PET (e.g., pacemaker, ferromagnetic implant, claustrophobia)
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Women breastfeeding
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Protected or restricted person (administratively or in judicial terms)
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Participants to another study with radiations or radiotracers since less of one year, participants to a concomitant study
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Do not speak french
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Service de neurologie C Hôpital neurologique Pierre Wertheimer/GHE Hospices Civils de Lyon | Bron | France | 69677 | |
2 | Centre de Référence Syndrome Gilles de la Tourette Département de Neurologie Pôle des Maladies du Système Nerveux Hôpital de la Pitié-Salpêtrière | Paris | France | 75013 |
Sponsors and Collaborators
- Hospices Civils de Lyon
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 69HCL22_0683