Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias (AMEDYST)
Primary Purpose
Dystonia
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
transcranial magnetic stimulation of the cerebellum
Sponsored by
About this trial
This is an interventional basic science trial for Dystonia focused on measuring Cerebellum, Striatum, Human, fMRI, Transcranial magnetic stimulation, Genetic dystonia
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Sham Comparator
Active Comparator
Arm Label
Sham cerebellar stimulation
Real cerebellar stimulation
Arm Description
Participants will receive a Sham stimulation (inefficient probe) applied over the cerebellum.
Participants will receive a real continuous theta burst stimulation (cTBS) applied over the cerebellum.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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
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.
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
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
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)
Full Information
NCT ID
NCT03481491
First Posted
March 20, 2018
Last Updated
March 27, 2018
Sponsor
Institut National de la Santé Et de la Recherche Médicale, France
1. Study Identification
Unique Protocol Identification Number
NCT03481491
Brief Title
Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias
Acronym
AMEDYST
Official Title
Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Unknown status
Study Start Date
May 4, 2018 (Anticipated)
Primary Completion Date
July 3, 2021 (Anticipated)
Study Completion Date
July 3, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut National de la Santé Et de la Recherche Médicale, France
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dystonia
Keywords
Cerebellum, Striatum, Human, fMRI, Transcranial magnetic stimulation, Genetic dystonia
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Masking Description
Participants will be blinded to the TMS procedure (SHAM or real stimulation).
Allocation
Non-Randomized
Enrollment
104 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sham cerebellar stimulation
Arm Type
Sham Comparator
Arm Description
Participants will receive a Sham stimulation (inefficient probe) applied over the cerebellum.
Arm Title
Real cerebellar stimulation
Arm Type
Active Comparator
Arm Description
Participants will receive a real continuous theta burst stimulation (cTBS) applied over the cerebellum.
Intervention Type
Other
Intervention Name(s)
transcranial magnetic stimulation of the cerebellum
Intervention Description
The intervention will consist in a continuous theta burst stimulation of the cerebellum under neuronavigation.
Primary Outcome Measure Information:
Title
Resting state functional connectivity between the cerebellum and the striatum
Description
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)
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Amplitude of Low Frequency Fluctuation (ALFF) of blood oxygen level-dependent signal in the cerebellum
Description
ALFF of Blood oxygen level-dependent signal in the cerebellum will be compared between the 3 groups (healthy controls, ADCY5 patients, PRTT2 patients
Time Frame
6 weeks
Title
Fractional anisotropy (FA) of the cerebello-striatal tract
Description
FA of the disynaptic tract between the cerebellum and the striatum will be compared between the 3 groups.
Time Frame
1 day
Title
Creatine concentration in the striatum measured with diffusion weighted spectroscopy.
Description
Creatine concentration in the striatum measured from the spectroscopy, will be compared between the 3 groups
Time Frame
6 weeks
Title
Amplitude of Low Frequency Fluctuation (ALFF) of blood oxygen level-dependent signal in the striatum
Description
ALFF of Blood oxygen level-dependent signal in the striatum will be compared between the 3 groups (healthy controls, ADCY5 patients, PRTT2 patients
Time Frame
6 weeks
Title
Resting state functional connectivity between the cerebellum and the thalamus
Description
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)
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
183 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emmanuel Flamand-Roze, MD, PhD
Phone
+33(0)142 16 27 48
Email
emmanuel.flamand-roze@psl.aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Karim Ammour
Phone
+33(0)144 23 60 67
Email
karim.ammour@inserm.fr
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35058336
Citation
Ekmen A, Meneret A, Valabregue R, Beranger B, Worbe Y, Lamy JC, Mehdi S, Herve A, Adanyeguh I, Temiz G, Damier P, Gras D, Roubertie A, Piard J, Navarro V, Mutez E, Riant F, Welniarz Q, Vidailhet M, Lehericy S, Meunier S, Gallea C, Roze E. Cerebellum Dysfunction in Patients With PRRT2-Related Paroxysmal Dyskinesia. Neurology. 2022 Mar 8;98(10):e1077-e1089. doi: 10.1212/WNL.0000000000200060. Epub 2022 Jan 20.
Results Reference
derived
Learn more about this trial
Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias
We'll reach out to this number within 24 hrs