Clinical trial NCT05136495: Assessment of ADCY5-related Movement Disorders With Motion SENSors
Official title: Assessment of ADCY5-related Movement Disorders With Motion SENSors: a Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: ADCY5-related Dyskinesia
Keywords: ADCY5
COFFEE
movement disorders
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-11-29
Enrollment: 2
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: ADCY5-related movement disorders are caused by dominant mutations in the ADCY5 gene. This rare neurogenetic disease is characterized by childhood-onset generalized hyperkinetic movements. Currently, the only tools available to rate the severity of movement disorders observed in ADCY5-patients are clinical rating scales of abnormal movements. These scales use the investigators' judgement to rate globally the severity of movements observed in various body parts of the patient. This protocol proposes to investigate a multimodal approach, combining a clinical scale assessment with ViconTM's objective movement measurement. A secondary objective of the study is to assess the effect of coffee on ADCY5-patients.

Detailed description: ADCY5-related movement disorders are caused by dominant mutations in the ADCY5 gene. This rare neurogenetic disease is characterized by childhood-onset generalized hyperkinetic movements. The abnormal movements typically comprise a combination of dystonia, myoclonus and chorea occurring on a background of axial hypotonia, with superimposed disabling episodes of paroxysmal dyskinesia. The causing mutations are located in the ADCY5 gene coding for the Adenylate Cyclase 5 (AC5). AC5 is highly expressed in the striatal projection neurons of the striatum, a region involved in the control of movements. No effective treatment has been found. Currently, the only tools available to rate the severity of movement disorders observed in ADCY5-patients are clinical rating scales of abnormal movements. These scales use the investigators' judgement to globally rate movements severity in various body parts. This leads to inter-raters' scoring variability. An objective assessment through refined and comprehensive quantification of movements is needed. A motion capture system, such as ViconTM, could better reflect the global and focal variations of abnormal movements. This would be critical for the evaluation of responses to potential treatments. This protocol proposes to investigate a multimodal approach, combining a clinical scale assessment with ViconTM's objective movement measurement. A secondary objective of the study is to assess the effect of coffee on ADCY5-patients. The caffeine contained in coffee acts as a nonselective adenosine receptor antagonist, with a strong affinity for A2A receptors. By blocking A2A receptors, caffeine reduces the enzymatic activity of the altered mutated AC5 protein coded by the mutated ADCY5 gene. This effect could modulate the abnormal movements observed in patients.

Eligibility criteria: Inclusion Criteria:

* ADCY5 mutation carriers
* Age \> 15 years old and 3 months
* Informed consent from the patient or/ and a legal representative when appropriate
* Affiliated with a social security system or beneficiary of such a regime or by waiver from CPP ( french ethic committee) for patients outside the European union ( EU)
* daily caffeine consumer

Exclusion Criteria:

* Hypersensitivity to caffeine or to xanthine derivatives
* Heart condition contraindicating coffee intake
* Liver failure
* Impaired comprehension interfering with an informed consent
* Positive pregnancy test for women of childbearing potential
* Patient treated by Enoxacin, Ciprofloxacin, Norfloxacin (Noroxin), Cimetidine, Phenytoin β-adrenergic drugs (β2 mimetics) at inclusion.

Primary outcomes:
measure: Quantification movement disorders
timeFrame: 24 HOURS
Secondary outcomes:
measure: Coffee effects
timeFrame: 24 Hours
measure: Involuntary scales evaluation
timeFrame: 24 Hours
measure: Dyskinesia impairment evaluation
timeFrame: 24 Hours
measure: Dyskinesia Rating Scale evaluation
timeFrame: 24 Hours
Other outcomes:
Locations:
city: Paris
country: France
facility: CIC Neurosciences, GH Pitié-Salpêtrière
Study officials:
References: