Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias

Dystonia Clinical Trial

— AMEDYST  

Official title:

Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03481491
• Other study ID #: C16-128
• Secondary ID: 2017-A01843-50
• Status: Not yet recruiting
• Phase: N/A
• First received: March 20, 2018
• Last updated: March 27, 2018
• Start date: May 4, 2018
• Est. completion date: July 3, 2022

Study information

• Verified date: March 2018
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Emmanuel Flamand-Roze, MD, PhD
• Phone: +33(0)142 16 27 48
• Email: emmanuel.flamand-roze[@]psl.aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will study the relationship between the basal ganglia and the cerebellum in dystonia by associating cerebellar stimulations with functional magnetic resonance imaging analysis.

Description:

Although dysfunctions in both basal ganglia and cerebellum in dystonia are well documented, the functional relationships between these two important motor control networks remains unclear in the context of dystonia. Here the investigators propose to tackle this issue by associating cerebellar stimulations with functional analysis using fMRI in dystonic patients.

The working hypothesis is that the primary torsion dystonia (PTD) pathophysiology involves dysfunction of striatum that is amplified by dysregulation of the cerebello-thalamo-striatal pathway.

The project is to study dystonia forms resulting primarily from dysfunctions of the striatum (patients with mutation of the ADCY5 gene) and compare them with patients with putative dysfunction of the cerebellum (patients with mutation of the PRRT2 gene) and healthy controls. In these patients, the investigators will look for (1) how cerebello-thalamo striatal pathway can be influenced by striatal dysfunctions and (2) whether cerebellar stimulation may prevent (or worsen?) the disrupted activity in the basal ganglia and (3) whether striatum-related dystonia share the same abnormal network with another form of dystonia resulting from another dysfunction (patients with PRRT2 mutation).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 104
• Est. completion date: July 3, 2022
• Est. primary completion date: July 3, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 183 Months and older

Eligibility

Inclusion Criteria:

• clinical diagnosis of Dystonia

• characterized ADCY5 or PRRT2 mutation

• must have a European Social Security card or a parent having an European Social Security card

• must be older than > 15 years 3 months

• must be able to give informed consent or, for minor patients, parents must be able to give informed consent

• must be able to comply with all study procedures, based on the judgment by the investigator(s).

Exclusion Criteria:

• major depression or any major mental disorders (axis I disorders)

• neurologic disorder other than dystonia

• presence of pacemaker, intracardiac lines, implanted pumps or stimulators, or metal objects inside the eye or skull, cochlear implant

• Permanent makeup of lips or eyelids

• Black large tattoo close to the head

• Severe claustrophobia

• Current pregnancy or breast feeding

• Copper intrauterine device Subjects with one of the following exclusion criteria will not receive cerebellar stimulation

• Open scalp wounds or scalp infection,

• epilepsy or seizures

• Taking at the time of the study: ketamine, antidepressants, ganciclovir, ritonavir, amphetamines, antiemetic.

Related Conditions & MeSH terms

• Dystonia
• Dystonic Disorders

Intervention

Other:
• transcranial magnetic stimulation of the cerebellum
The intervention will consist in a continuous theta burst stimulation of the cerebellum under neuronavigation.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Resting state functional connectivity between the cerebellum and the striatum	Synchrony between the cerebellum and the striatum, calculated from resting state fMRI done at visit2 will be compared between the 3 groups (healthy controls, ADCY5 patients, PRTT2 patients)	6 weeks
Secondary	Amplitude of Low Frequency Fluctuation (ALFF) of blood oxygen level-dependent signal in the cerebellum	ALFF of Blood oxygen level-dependent signal in the cerebellum will be compared between the 3 groups (healthy controls, ADCY5 patients, PRTT2 patients	6 weeks
Secondary	Fractional anisotropy (FA) of the cerebello-striatal tract	FA of the disynaptic tract between the cerebellum and the striatum will be compared between the 3 groups.	1 day
Secondary	Creatine concentration in the striatum measured with diffusion weighted spectroscopy.	Creatine concentration in the striatum measured from the spectroscopy, will be compared between the 3 groups	6 weeks
Secondary	Amplitude of Low Frequency Fluctuation (ALFF) of blood oxygen level-dependent signal in the striatum	ALFF of Blood oxygen level-dependent signal in the striatum will be compared between the 3 groups (healthy controls, ADCY5 patients, PRTT2 patients	6 weeks
Secondary	Resting state functional connectivity between the cerebellum and the thalamus	Synchrony between the cerebellum and the thalamus, calculated from resting state fMRI done at visit2 will be compared between the 3 groups (healthy controls, ADCY5 patients, PRTT2 patients)	6 weeks