Investigations of the Pathophysiology of Gilles de la Tourette Syndrome. Part 2: 7T MRI

NCT05233306 | Completed

• 1 other identifier: PETMR_GTS_2-7T-MRI
• Study Type: observational
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

Gilles de la Tourette syndrome (GTS; also known as Tourette syndrome) is a congenital neuropsychiatric disorder. Characteristic symptoms are so-called tics-rapid, repetitive movements (motor tics) or vocalizations (vocal tics) that start suddenly without any apparent purpose. Previous research supports the hypothesis of defective regulation (dysregulation) of the dopaminergic system, with particular discussion of dysfunction of tonic/phasic dopamine release or dopaminergic hyperinnervation. Moreover, given the complex interaction of different neurotransmitters, especially in the basal ganglia, it can be assumed that abnormal dopaminergic transmission also affects other transmitter systems, such as glutamate (Glu) or γ-aminobutyrate (GABA). Furthermore, recent results suggest an abnormality in cerebral iron metabolism in GTS. Since iron is accumulated in dopamine vesicles and plays a central role in dopamine synthesis, this observation may also be related to dysfunction of the dopaminergic system. Therefore, in this multimodal study, the investigators aim to combine positron emission tomography (PET), magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS) methods comparing patients with GTS and a control cohort. In Part 2 of this study, MRI and MRS at 7 Tesla are employed to investigate (i) the concentrations of Glu, glutamine and GABA in the corpus striatum and the cortex cingularis anterior and (ii) the subcortical iron concentration.

Conditions

Gilles de la Tourette Syndrome; Tourette Syndrome

Keywords

magnetic resonance imaging; magnetic resonance spectroscopy

Outcome Measures

Primary Outcomes (5)

• Subcortical magnetic susceptibility as brain iron proxy

  Iron stores in subcortical structures are changed in GTS patients

  Susceptibility is measured through study completion, an average of 6 months

• Effective transverse relaxation rate, R2*, as brain iron proxy

  R2\* in subcortical structures is changed in GTS patients

  R2* is measured through study completion, an average of 6 months

• Concentration of glutamate (Glu) and glutamate plus glutamine (Glx)

  Glu and Glx levels are changed in GTS patients in striatum and cingulate cortex

  Glu and Glx are measured through study completion, an average of 6 months

• Concentration of glutamine (Gln)

  Gln levels are changed in GTS patients in striatum and cingulate cortex

  Gln is measured through study completion, an average of 6 months

• Concentration of γ-aminobutyrate (GABA)

  GABA levels are changed in GTS patients in striatum and cingulate cortex

  GABA is measured through study completion, an average of 6 months

Secondary Outcomes (1)

• Plasma ferritin level

  A plasma sample is analyzed through study completion, an average of 6 months

Study Arms (2)

GTS patient group

Cohort of adult GTS patients, males and females, age range 18 to 50 years

Device: MRI scanner (7 Tesla)

Control group

Cohort of healthy control subjects, males and females, age range 18 to 50 years

Device: MRI scanner (7 Tesla)

Interventions

MRI scanner (7 Tesla) DEVICE

MRI and MRS examination at 7 Tesla; protocol duration of approx. 75 min

Control group; GTS patient group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

GTS group selected from primary care clinic and by advertisement in GTS patient organizations Control group selected from database of the MPI and advertisement

You may qualify if:

• GTS according to DSM-IV-TR criteria
• mild or moderate tics
• drug-free for a minimum of 4 weeks prior to the exam

You may not qualify if:

• severe tics of the head and/or face
• psychiatric medication within 4 weeks prior to the exam
• consumption of alcohol during 24 hours prior to the exam
• consumption of cannabis during 24 hours prior to the exam
• pregnancy
• general contra-indications for MRI exams
• Control Group:
• no known neurological or psychiatric disease
• psychiatric medication within 4 weeks prior to the exam
• consumption of alcohol during 24 hours prior to the exam
• consumption of cannabis during 24 hours prior to the exam
• pregnancy
• general contra-indications for MRI exams

Sponsors & Collaborators

• Max Planck Institute for Human Cognitive and Brain Sciences: lead
• Hannover Medical School: collaborator
• Leipzig University Medical Center: collaborator

Study Sites (1)

Max Planck Institute for Human Cognitive and Brain Sciences

Leipzig, 04103, Germany

Location

Related Publications (19)

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  PMID: 27601976 BACKGROUND

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  PMID: 11830757 BACKGROUND

• Draper A, Stephenson MC, Jackson GM, Pepes S, Morgan PS, Morris PG, Jackson SR. Increased GABA contributes to enhanced control over motor excitability in Tourette syndrome. Curr Biol. 2014 Oct 6;24(19):2343-7. doi: 10.1016/j.cub.2014.08.038. Epub 2014 Sep 25.

  PMID: 25264251 BACKGROUND

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• Kaller S, Rullmann M, Patt M, Becker GA, Luthardt J, Girbardt J, Meyer PM, Werner P, Barthel H, Bresch A, Fritz TH, Hesse S, Sabri O. Test-retest measurements of dopamine D1-type receptors using simultaneous PET/MRI imaging. Eur J Nucl Med Mol Imaging. 2017 Jun;44(6):1025-1032. doi: 10.1007/s00259-017-3645-0. Epub 2017 Feb 14.

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  PMID: 14673893 BACKGROUND

• Larsen B, Olafsson V, Calabro F, Laymon C, Tervo-Clemmens B, Campbell E, Minhas D, Montez D, Price J, Luna B. Maturation of the human striatal dopamine system revealed by PET and quantitative MRI. Nat Commun. 2020 Feb 12;11(1):846. doi: 10.1038/s41467-020-14693-3.

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  PMID: 22577221 BACKGROUND

• Maia TV, Conceicao VA. Dopaminergic Disturbances in Tourette Syndrome: An Integrative Account. Biol Psychiatry. 2018 Sep 1;84(5):332-344. doi: 10.1016/j.biopsych.2018.02.1172. Epub 2018 Mar 9.

  PMID: 29656800 BACKGROUND

• Mink JW. Basal ganglia dysfunction in Tourette's syndrome: a new hypothesis. Pediatr Neurol. 2001 Sep;25(3):190-8. doi: 10.1016/s0887-8994(01)00262-4.

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• Moller HE, Bossoni L, Connor JR, Crichton RR, Does MD, Ward RJ, Zecca L, Zucca FA, Ronen I. Iron, Myelin, and the Brain: Neuroimaging Meets Neurobiology. Trends Neurosci. 2019 Jun;42(6):384-401. doi: 10.1016/j.tins.2019.03.009. Epub 2019 Apr 29.

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• Okubo Y, Suhara T, Suzuki K, Kobayashi K, Inoue O, Terasaki O, Someya Y, Sassa T, Sudo Y, Matsushima E, Iyo M, Tateno Y, Toru M. Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature. 1997 Feb 13;385(6617):634-6. doi: 10.1038/385634a0.

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• Singer HS. Treatment of tics and tourette syndrome. Curr Treat Options Neurol. 2010 Nov;12(6):539-61. doi: 10.1007/s11940-010-0095-4.

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• Singer HS, Morris C, Grados M. Glutamatergic modulatory therapy for Tourette syndrome. Med Hypotheses. 2010 May;74(5):862-7. doi: 10.1016/j.mehy.2009.11.028. Epub 2009 Dec 21.

  PMID: 20022434 BACKGROUND

• Tinaz S, Belluscio BA, Malone P, van der Veen JW, Hallett M, Horovitz SG. Role of the sensorimotor cortex in Tourette syndrome using multimodal imaging. Hum Brain Mapp. 2014 Dec;35(12):5834-46. doi: 10.1002/hbm.22588. Epub 2014 Jul 15.

  PMID: 25044024 BACKGROUND

• Yoon DY, Gause CD, Leckman JF, Singer HS. Frontal dopaminergic abnormality in Tourette syndrome: a postmortem analysis. J Neurol Sci. 2007 Apr 15;255(1-2):50-6. doi: 10.1016/j.jns.2007.01.069. Epub 2007 Mar 6.

  PMID: 17337006 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

MeSH Terms

Conditions

Tourette Syndrome

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tic Disorders; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Harald E Möller, PhD

  Max Planck Institute for Human Cognitive and Brain Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2022
• First Posted: February 10, 2022
• Study Start: January 27, 2022
• Primary Completion: April 6, 2023
• Study Completion: July 7, 2023
• Last Updated: March 29, 2024

Record last verified: 2024-03

Locations

DE (1)