ADCY5-related Dyskinesia
Conditions
Keywords
ADCY5, COFFEE, movement disorders
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.
Interventions
OTHERcaffeinated coffee - decaffeinated coffee
Drink caffeinated coffee one morning and drink decaffeinated coffee the other morning
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantification movement disorders | 24 HOURS | Assessment of correlation between displacement data using the ViconTM system and standardized clinical scales' scores of movements |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Coffee effects | 24 Hours | Change in abnormal movements, measured with motion sensors (ViconTM system) after caffeinated coffee vs after decaffeinated coffee |
| Involuntary scales evaluation | 24 Hours | Change in abnormal movements, measured with standardized clinical scale (Abnormal Involuntary Movement Scale (AIMS; Global score range 0 to 28 and severity subscore range 0 to 4; higher scores mean worse outcome), after caffeinated coffee vs after decaffeinated coffee |
| Dyskinesia impairment evaluation | 24 Hours | Change in abnormal movements, measured with standardized clinical scale Dyskinesia Impairment Scale (DIS) (total score range 0 to 288; higher scores mean worse outcome) after caffeinated coffee vs after decaffeinated coffee |
| Dyskinesia Rating Scale evaluation | 24 Hours | Change in abnormal movements, measured with standardized clinical scale Unified Dyskinesia Rating Scale (UDysRS) (total score range of 0 to 104; higher scores mean worse outcome), after caffeinated coffee vs after decaffeinated coffee |
Countries
France
Outcome results
None listed