DystoniaAMEDYSTNCT03481491
Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias
A study testing transcranial magnetic stimulation of the cerebellum in people with Dystonia, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 15 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Dystonia
- What is being tested?
- transcranial magnetic stimulation of the cerebellum
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 1 siteFrance
- Study dates
- 6 Aug 2018to 4 Aug 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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).
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
France1 site
Département de Neurologie, Fédération des Maladies du Système Nerveux, GH Pitié-Salpêtrière, 47 Bd de l'Hôpital
Paris
About this study
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.
Read the 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).
- Conditions
- Dystonia
- Being tested
- transcranial magnetic stimulation of the cerebellum
- Keywords
- Cerebellum, Striatum, Human, fMRI, Transcranial magnetic stimulation, Genetic dystonia
- Medical subject headings
- Dystonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcranial magnetic stimulation of the cerebellumOther
The intervention will consist in a continuous theta burst stimulation of the cerebellum under neuronavigation.
| Study group | Role | What they receive |
|---|---|---|
| Sham cerebellar stimulation | Sham comparator | Participants will receive a Sham stimulation (inefficient probe) applied over the cerebellum. Receives: Other: transcranial magnetic stimulation of the cerebellum |
| Real cerebellar stimulation | Active comparator | Participants will receive a real continuous theta burst stimulation (cTBS) applied over the cerebellum. Receives: Other: transcranial magnetic stimulation of the cerebellum |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 6 weeks
Secondary outcomes (5)
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
Measured: 6 weeks
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.
Measured: 1 day
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
Measured: 6 weeks
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
Measured: 6 weeks
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)
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2018
- Study start6 Aug 2018
- Primary completion4 Aug 2023
- Study completion4 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DystoniaStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Emmanuel Flamand-Roze, MD, PhD, Principal investigator, Pitié-Salpêtrière
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03481491
- Sponsor's protocol ID
- C16-128
- Other IDs
- 2017-A01843-50
- Acronym
- AMEDYST
- Status last verified
- Jan 2025
- First submitted
- 20 Mar 2018
- Last updated
- 18 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35058336Ekmen A, Doulazmi M, Meneret A, Jegatheesan P, Herve A, Damier P, Gras D, Roubertie A, Piard J, Mutez E, Tarrano C, Welniarz Q, Vidailhet M, Worbe Y, Gallea C, Roze E. Non-Motor Symptoms and Quality of Life in Patients with PRRT2-Related Paroxysmal Kinesigenic Dyskinesia. Mov Disord Clin Pract. 2023 Jun 5;10(7):1082-1089. doi: 10.1002/mdc3.13795. eCollection 2023 Jul.
PubMed 37476308
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias
- ClinicalTrials.gov ID
- NCT03481491
- Acronym / sponsor ID
- AMEDYST / C16-128
- Conditions
- Dystonia
- Keywords
- Cerebellum, Striatum, Human, fMRI, Transcranial magnetic stimulation, Genetic dystonia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- 6 Aug 2018 (actual)
- Primary completion
- 4 Aug 2023 (actual)
- Study completion
- 4 Aug 2024 (actual)
- First posted
- 29 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sham cerebellar stimulation | Sham comparator | Other: transcranial magnetic stimulation of the cerebellumParticipants will receive a Sham stimulation (inefficient probe) applied over the cerebellum. |
| Real cerebellar stimulation | Active comparator | Other: transcranial magnetic stimulation of the cerebellumParticipants will receive a real continuous theta burst stimulation (cTBS) applied over the cerebellum. |
Who may qualify
- Ages
- 15 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| transcranial magnetic stimulation of the cerebellumThe intervention will consist in a continuous theta burst stimulation of the cerebellum under neuronavigation. | Other | Real cerebellar stimulation, Sham cerebellar stimulation |
Primary outcome
Resting state functional connectivity between the cerebellum and the striatum
Time frame: 6 weeks
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)
5 secondary outcomes
Amplitude of Low Frequency Fluctuation (ALFF) of blood oxygen level-dependent signal in the cerebellum
Time frame: 6 weeks
Fractional anisotropy (FA) of the cerebello-striatal tract
Time frame: 1 day
Creatine concentration in the striatum measured with diffusion weighted spectroscopy.
Time frame: 6 weeks
Amplitude of Low Frequency Fluctuation (ALFF) of blood oxygen level-dependent signal in the striatum
Time frame: 6 weeks
Resting state functional connectivity between the cerebellum and the thalamus
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2025.
- Results publication: PubMed 35058336Ekmen 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 publication: PubMed 37476308Ekmen A, Doulazmi M, Meneret A, Jegatheesan P, Herve A, Damier P, Gras D, Roubertie A, Piard J, Mutez E, Tarrano C, Welniarz Q, Vidailhet M, Worbe Y, Gallea C, Roze E. Non-Motor Symptoms and Quality of Life in Patients with PRRT2-Related Paroxysmal Kinesigenic Dyskinesia. Mov Disord Clin Pract. 2023 Jun 5;10(7):1082-1089. doi: 10.1002/mdc3.13795. eCollection 2023 Jul.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emmanuel Flamand-Roze, MD, PhD principal investigator
Pitié-Salpêtrière
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing transcranial magnetic stimulation of the cerebellum in people with Dystonia, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resting state functional connectivity between the cerebellum and the striatum (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03481491, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2025.