Caffeine Efficacy in ADCY5-related Dyskinesia
- Conditions
- ADCY5-related Dyskinesia
- Interventions
- Other: caffeine and movement disorders
- Registration Number
- NCT04469283
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
Heterozygous mutations in ADCY5 induce hyperactivity of striatal adenylate cyclase type 5 (AC5), manifesting as early-onset hyperkinetic movement disorders. Numerous treatments have been tried without much efficacy thus far. Two patients from the same family reported efficacy of caffeine on paroxysmal episodes, both to prevent episodes and to reduce their duration (efficacy estimated to be around 80%), which was specific to caffeine as it was reproduced with caffeine citrate capsules. Interestingly, there is a rationale underlying this observation. Indeed, caffeine is an antagonist of adenosine A2A receptors (A2AR), which activate AC5 and are localized preferentially in striatal neurons that express dopamine receptors D2 .Caffeine therefore likely induces AC5 inhibition, and thus clinical improvement in patients with hyperactivity of this protein. This observation has been recently published in2019.
The investigators will collect preliminary data by interviewing our neurologist and neuropediatric colleagues, in France and abroad since it is a rare disease, on the effect of caffeine on motor symptoms and global clinical status in their ADCY5 patients.
- Detailed Description
Heterozygous mutations in ADCY5 induce hyperactivity of striatal adenylate cyclase type 5 (AC5) manifesting as early-onset hyperkinetic movement disorders. The phenotype combines chorea, dystonia and/or myoclonus with frequent facial involvement, axial hypotonia, fluctuations and/or episodes of paroxysmal dyskinesia which can be nocturnal and/or painful, generally without intellectual deficiency, epilepsy or cerebellar syndrome . It is a very rare disease, affecting around twenty patients in France.
Scientific context of the research:
Numerous treatments have been tried without much efficacy thus far.
Scientific justification for the study:
Two patients from the same family reported efficacy of caffeine on paroxysmal episodes, both to prevent episodes and to reduce their duration (efficacy estimated to be around 80%), which was specific to caffeine as it was reproduced with caffeine citrate capsules. Interestingly there is a rationale underlying this situation. Indeed, caffeine is an antagonist of adenosine A2A receptors (A2AR), which activate AC5 and are localized preferentially in striatal neurons that express dopamine receptors D2. Caffeine therefore likely induces inhibition of AC5, and thus clinical improvement in patients with hyperactivity of this protein. This observation has been recently published in 2019 HYPOTHESIS Our hypothesis is that most patients with ADCY5-related dyskinesia respond well to caffeine.
This study is a multicentric retrospective study, which will be conducted in neurology and neuropediatric departments across the world.
Participants will be recruited by their own physician. This research will take place over 18 months in total: 12 month to collect all patients' data and 6 months to analyse data.
The number of participants will be between 5 and 20, depending on colleagues replies.
This research will take place over 18 months in total: 12 month to collect all patients' data and 6 months to analyse data.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description caffeine efficacy caffeine and movement disorders Collection of preliminary data on caffeine efficacy on movement disorders in patients with ADCY5-related dyskinesia.
- Primary Outcome Measures
Name Time Method Percentage of responders to caffeine 12 months the response being defined as an improvement of overall involuntary movements of 40% or more.
- Secondary Outcome Measures
Name Time Method Global improvement of involuntary movements, 12 MONTHS Global change of involuntary movements ranging from 0 (no change) to 10 (disappearance of involuntary movements)
Duration of paroxysmal episodes of movement disorders 12 months Change of the duration of paroxysmal episodes of movement disorders with caffeine
Global clinical change 12 months Global clinical change ranging from 0 (no change) to 10 (normalization of the global clinical state)