Sensorimotor Integration in Monogenic Parkinson-dystonia Syndromes (SensoMo-PD)

June 21, 2023 updated by: Anne Weißbach, University Hospital Schleswig-Holstein

SensoMo-PD: Sensorimotor Integration in Monogenic Parkinson-dystonia Syndromes

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Monogenic Parkinson-dystonia syndromes are rare but very valuable model disorders for genetically undefined syndromes, as their genetic cause, i.e., pathogenic gene variants, have been identified. For certain subtypes, even the neuroanatomical basis was discovered. Despite the different genetic and anatomical characteristics, a strong clinical overlap was reported between PARK-Parkin/PARK-PINK1, DYT/PARK-GCH1, and DYT/PARK-TAF1.

Interestingly, previous research in these different Parkinson-dystonia syndromes suggests a distinct pattern of neurophysiological alterations within the primary motor and premotor-motor network for each syndrome. Even asymptomatic, heterozygous mutation carriers, show abnormalities within neurophysiological and in addition, functional, metabolic, and structural imaging studies.

In general, a better clinical and neurophysiological evaluation of asymptomatic compared to symptomatic mutation carriers and healthy controls across subgroups is warranted. However, the number of mutation carriers per subgroup is limited and some are unable to travel to Lübeck to participate in research. To increase the participant size, in addition to the examination in our neurophysiological laboratory, the investigators want to visit and investigate some mutation carriers in their home environment with a mobile examination unit. In this regard, the transcranial magnetic stimulation paradigm of short-latency afferent inhibition (SAI) is of great interest as it can reliably capture the effects of sensory input (median nerve stimulation) on motor output (MEP amplitude) without complex neuronavigation. Additionally, a video-based clinical examination will be performed, which will be rated offline in a blinded fashion by movement disorder specialists to correlate SAI with symptom severity.

Therefore, the proposed project will, for the first time, allow a direct comparison of sensorimotor integration deficits in correlation to clinical signs between three different monogenic Parkinson-dystonia syndromes. Furthermore, contrasting the findings between asymptomatic and symptomatic mutation carriers will help, on the one hand, to draw conclusions on potential protective markers, and on the other hand, to identify neurophysiological endophenotypes. Furthermore, successful completion of the project will generate clinically well-defined monogenic subgroups with particular sensorimotor abnormalities, who can serve as model disorders in further research projects that aim to characterize sensorimotor deficit in a cognitive framework and in a longitudinal fashion.

Study Type

Observational

Enrollment (Estimated)

120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Germany
    • Schleswig-Holstein
      • Lübeck, Schleswig-Holstein, Germany, 23562

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

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.

Description

Inclusion criteria for mutation carriers:

  • Pathogenic Parkin, PINK1, GCH1, or TAF1 gene variant
  • Age >18 years
  • Informed consent

Inclusion criteria for healthy control participants:

  • No movement disorder
  • Age >18 years
  • Informed consent
  • No medication with influences on the central nervous system

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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)
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.
Other: Video-based clinical examination
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.
Other: 24 hours drug withdrawal of dopaminergic medication
Examinations will be done under chronic dopaminergic treatment and after a 24 hours dopaminergic drug withdrawal.
Other: Evaluation of deep brain stimulation
Examinations will be done before and after implantation of deep brain stimulation (clinically optimal stimulation vs. switched off stimulation)
AMC DYT/PARK-TAF1
Asymptomatic mutation carriers (AMC) of the TAF1 gene will be examined.
Device: Transcranial magnetic stimulation (TMS)
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.
Other: Video-based clinical examination
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.
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)
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.
Other: Video-based clinical examination
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.
Other: 24 hours drug withdrawal of dopaminergic medication
Examinations will be done under chronic dopaminergic treatment and after a 24 hours dopaminergic drug withdrawal.
AMC DYT/PARK-GCH1
Asymptomatic mutation carriers (AMC) of the GCH1 gene will be examined.
Device: Transcranial magnetic stimulation (TMS)
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.
Other: Video-based clinical examination
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.
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)
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.
Other: Video-based clinical examination
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.
Other: 24 hours drug withdrawal of dopaminergic medication
Examinations will be done under chronic dopaminergic treatment and after a 24 hours dopaminergic drug withdrawal.
AMC PARK-Parkin/PARK-PINK1
Asymptomatic mutation carriers (SMC) of the Parkin or PINK1 genes will be examined.
Device: Transcranial magnetic stimulation (TMS)
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.
Other: Video-based clinical examination
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.
Control group
A healthy control group will be examined.
Device: Transcranial magnetic stimulation (TMS)
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.
Other: Video-based clinical examination
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Contrast sensorimotor integration in patients with three different monogenic Parkinson-dystonia syndromes.
Time Frame: Two timepoints (if applicable): With chronic dopaminergic medication vs. 24h drug withdrawal OR before and after deep brain stimulation implantation
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.
Time Frame: One timepoint
Video based clinical examination
One timepoint
Correlate clinical symptom severity with changes in sensorimotor integration.
Time Frame: Two timepoints (patients) or one timepoint (asymptomatic mutation carriers and healthy control participants)
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.
Time Frame: Two timepoints (if applicable): With chronic dopaminergic medication vs. 24h drug withdrawal OR before and after deep brain stimulation implantation
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Schleswig-Holstein

Collaborators

Michael J. Fox Foundation for Parkinson's Research

Investigators

  • Principal Investigator: Anne Weissbach, MD, Institute of Systems Motor Science

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2023

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

January 27, 2023

First Submitted That Met QC Criteria

January 27, 2023

First Posted (Actual)

February 6, 2023

Study Record Updates

Last Update Posted (Actual)

June 23, 2023

Last Update Submitted That Met QC Criteria

June 21, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MJFF-022062

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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