Sensorimotor Integration in Monogenic Parkinson-dystonia Syndromes

NCT05713721 | Unknown

• 1 other identifier: MJFF-022062
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Hereditary Parkinson and dystonia syndromes are rare, as are people who carry the predisposition for Parkinson or dystonia but do not have symptoms. It is particularly important to study these people because they are a good model for understanding the development of common non-hereditary Parkinson's and dystonia. To do this, the investigators want to look at how the brain works and how different areas of the brain communicate with each other. The investigators want to identify differences in brain regions connecting perception and action between mutation carriers that develop clinical symptoms and those who stay healthy in different subgroups of inherited Parkinson-dystonia syndromes. Mutation carriers with and without symptoms of three different inherited Parkinson-dystonia syndromes will be investigated at their homes with the help of a mobile examination unit. To detect even subtle signs, which the mutation carriers might not even be aware of, the investigators will use a detailed video-based and -documented movement examination and a non-invasive magnetic stimulation technique that investigates how a sensory, i.e., electrical stimulus can influence the motor response in a hand muscle. Our study will allow the investigators, on the one hand, to define specific markers that protect some mutation carriers from having clinical symptoms and, on the other hand, to identify neurophysiological characteristics that all mutation carriers share whether or not they have clinical symptoms. These are important information for a better understanding of the basis of these disorders and for the development of new treatment strategies, which can also be transferred to genetically-undefined Parkinson's and dystonia syndromes. Through this study, large groups of mutation carriers that have received an in-depth clinical and neurophysiological examination and can be investigated longitudinally in future studies will be build up.

Conditions

Parkinson; Dystonia; DYT3; DYT5; PINK1 Gene Deletion; Dystonia, Familial

Keywords

Dystonia; Parkinson's; Parkinson-dystonia; GCH1; Parkin; PINK1; TAF1; XDP; X-linked Dystonia-Parkinsonism

Outcome Measures

Primary Outcomes (4)

• Contrast sensorimotor integration in patients with three different monogenic Parkinson-dystonia syndromes.

  Transcranial magnetic stimulation (short-latency afferent inhibition)

  Two timepoints (if applicable): With chronic dopaminergic medication vs. 24h drug withdrawal OR before and after deep brain stimulation implantation

• Define whether asymptomatic mutation carriers show abnormalities in sensorimotor integration and clinical signs of Parkinson and dystonia upon video examination.

  Video based clinical examination

  One timepoint

• Correlate clinical symptom severity with changes in sensorimotor integration.

  Transcranial magnetic stimulation (short-latency afferent inhibition) and Video based clinical examination

  Two timepoints (patients) or one timepoint (asymptomatic mutation carriers and healthy control participants)

• Evaluate treatment effects on sensorimotor integration, e.g., for PARK-Parkin/PARK-PINK1 and DYT/PARK-GCH1 chronic dopaminergic medication and for DYT/PARK-TAF1 deep brain stimulation effects.

  Transcranial magnetic stimulation (short-latency afferent inhibition)

  Two timepoints (if applicable): With chronic dopaminergic medication vs. 24h drug withdrawal OR before and after deep brain stimulation implantation

Study Arms (7)

SMC DYT/PARK-TAF1

Symptomatic mutation carriers (SMC) of the TAF1 gene, which is associated with X-linked Dystonia-Parkinsonism, will be examined.

Device: Transcranial magnetic stimulation (TMS); Other: Video-based clinical examination; Other: 24 hours drug withdrawal of dopaminergic medication; Other: Evaluation of deep brain stimulation

AMC DYT/PARK-TAF1

Asymptomatic mutation carriers (AMC) of the TAF1 gene will be examined.

Device: Transcranial magnetic stimulation (TMS); Other: Video-based clinical examination

SMC DYT/PARK-GCH1

Symptomatic mutation carriers (SMC) of the GCH1 gene, which is associated with dopa-responsive Dystonia, will be examined.

Device: Transcranial magnetic stimulation (TMS); Other: Video-based clinical examination; Other: 24 hours drug withdrawal of dopaminergic medication

AMC DYT/PARK-GCH1

Asymptomatic mutation carriers (AMC) of the GCH1 gene will be examined.

Device: Transcranial magnetic stimulation (TMS); Other: Video-based clinical examination

SMC PARK-Parkin/PARK-PINK1

Symptomatic mutation carriers (SMC) of the Parkin or PINK1 genes, which is associated with Parkinsonism, will be examined.

Device: Transcranial magnetic stimulation (TMS); Other: Video-based clinical examination; Other: 24 hours drug withdrawal of dopaminergic medication

AMC PARK-Parkin/PARK-PINK1

Asymptomatic mutation carriers (SMC) of the Parkin or PINK1 genes will be examined.

Device: Transcranial magnetic stimulation (TMS); Other: Video-based clinical examination

Control group

A healthy control group will be examined.

Device: Transcranial magnetic stimulation (TMS); Other: Video-based clinical examination

Interventions

Transcranial magnetic stimulation (TMS) DEVICE

TMS over the left primary motor cortex will be performed. To investigate sensorimotor integration, an electrical stimulus on the right index finger will precede the TMS pulse.

AMC DYT/PARK-GCH1; AMC DYT/PARK-TAF1; AMC PARK-Parkin/PARK-PINK1; Control group; SMC DYT/PARK-GCH1; SMC DYT/PARK-TAF1; SMC PARK-Parkin/PARK-PINK1

Video-based clinical examination OTHER

A standardized neurological examination will be performed and video taped. The videos will be rated by movement disorder specialists, wo are blinded for the symptom and mutation status of the participants.

AMC DYT/PARK-GCH1; AMC DYT/PARK-TAF1; AMC PARK-Parkin/PARK-PINK1; Control group; SMC DYT/PARK-GCH1; SMC DYT/PARK-TAF1; SMC PARK-Parkin/PARK-PINK1

24 hours drug withdrawal of dopaminergic medication OTHER

Examinations will be done under chronic dopaminergic treatment and after a 24 hours dopaminergic drug withdrawal.

SMC DYT/PARK-GCH1; SMC DYT/PARK-TAF1; SMC PARK-Parkin/PARK-PINK1

Evaluation of deep brain stimulation OTHER

Examinations will be done before and after implantation of deep brain stimulation (clinically optimal stimulation vs. switched off stimulation)

SMC DYT/PARK-TAF1

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We will include symptomatic and asymptomatic carriers of pathogenic variants in the Parkin, PINK1, GCH1, or TAF1 gene, and sex- and age-matched healthy controls.

You may qualify if:

• Pathogenic Parkin, PINK1, GCH1, or TAF1 gene variant
• Age \>18 years
• Informed consent
• No movement disorder
• Age \>18 years
• Informed consent
• No medication with influences on the central nervous system

You may not qualify if:

• Age \<18 years
• Pregnancy
• Epilepsy
• Medication that reduces the seizure threshold

Sponsors & Collaborators

• University Hospital Schleswig-Holstein: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (1)

Institute of Systems Motor Science Lübeck

Lübeck, Schleswig-Holstein, 23562, Germany

RECRUITING

MeSH Terms

Conditions

Dystonia; Dystonic Disorders; Parkinson Disease; Dystonia 3, Torsion, X-Linked

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Movement Disorders; Central Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Anne Weissbach, MD

  Institute of Systems Motor Science

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Weissbach, MD

CONTACT

+49 451 3101 8219; anne.weissbach@neuro.uni-luebeck.de

Feline Hamami, M. Sc.

CONTACT

+49 451 3101 8218; feline.hamami@neuro.uni-luebeck.de

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 27, 2023
• First Posted: February 6, 2023
• Study Start: January 1, 2023
• Primary Completion: June 30, 2024
• Study Completion: December 31, 2024
• Last Updated: June 23, 2023

Record last verified: 2023-06

Locations

DE (1)