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DyskinesiasCAF-ADCY5NCT04351360

Pilot Study on Caffeine Efficiency in ADCY5-related Dyskinesia

An observational study of Dyskinesias, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Heterozygous mutations in the ADCY5 gene cause involuntary early-onset hyperkinetic movements. In addition, patients may have associated psychiatric disorders.There is currently no treatment. Read more about this study

Who is it for?
Ages 8 years and older
Conditions the study is for
Dyskinesias
How many people
15 participants
Where
1 siteFrance
Study dates
15 May 2020to 6 May 2021
Phase
Observational
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 8 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Study population: Patients with ADCY5-related dyskinesia being actively treated, or who have been previously treated, with caffeine.

Who may be able to join

  • Proven genetic diagnosis of ADCY5-related dyskinesia
  • Caffeine intake
  • Non opposition by the patient or the legal representatives if the patient is a minor.
  • No Exclusion Criteria.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

France1 site

  • Département de Neurologie Groupe Hospitalier Pitié-Salpêtrière

    Paris, 75651 PARIS Cedex 13

Other trials in France

About this study

Official title: Pilot Study on Subjective Efficiency of Caffeine in ADCY5-related Dyskinesia

Heterozygous mutations in the ADCY5 gene cause involuntary early-onset hyperkinetic movements. In addition, patients may have associated psychiatric disorders.There is currently no treatment. As the pathophysiology is linked to ADCY5 hyperactivity, the investigative team has treated patients with caffeine, an antagonist. The investigator wishes to interview patients on the effect of caffeine on their motor symptoms and their overall clinical condition, and on the possible existence of psychiatric comorbidities using phone questionnaires.

Read the detailed description

Heterozygous mutations in the ADCY5 gene cause involuntary early-onset hyperkinetic movements. 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.

Many treatments have been tried, with no obvious efficacy. Two patients from the same family (a father and daughter) told investigators that caffeine had a dramatic effect on their paroxysmal episodes. They said that taking coffee would prevent episodes and reduce their duration (efficacy estimated at 80%), an effect specific to caffeine since it was reproduced by the ingestion of caffeine citrate capsules. Very interestingly, there is a rationale underlying this phenomenon. Indeed, caffeine is an antagonist of the adenosine A2A receptors (A2AR), receptors which activate ADCY5 and which are localized preferentially in striatal neurons expressing dopamine D2 receptors. As caffeine is an A2AR antagonist, it likely inhibits ADCY5, and therefore induces clinical improvement in patients with hyperactivity of this protein.

In addition, the investigative team noted anxiety in some of its patients, and the question of the presence of psychiatric disorders in ADCY5 patients was recently raised in the literature.

The investigative team wishes to collect standardized preliminary data by questioning patients on the effect of caffeine on their motor symptoms and their overall clinical state, and on the possible existence of psychiatric comorbidities using structured questionnaires which will be carried out by phone.

Conditions
Dyskinesias
Keywords
ADCY5 mutation
Medical subject headings
Dyskinesias

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of responders to caffeine

    the response being defined as an improvement of overall involuntary movements of 40% or more.

    Measured: one hour

Secondary outcomes (5)

  1. Global change of involuntary movements ranging from 0 (no change) to 10 (disappearance of involuntary movements)

    evaluated by patients

    Measured: one hour

  2. Global clinical change ranging from 0 (no change) to 10 (normalization of the global clinical state)

    evaluated by patients

    Measured: one hour

  3. Change of the duration of paroxysmal episodes of movement disorders with caffeine

    evaluated by patients

    Measured: one hour

  4. Frequency change of paroxysmal episodes of movement disorders with caffeine

    evaluated by patients

    Measured: one hour

  5. Presence or absence of psychiatric symptoms

    according to the MINI (Mini International Neuropsychiatric Interview)

    Measured: one hour

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2020
  2. Study start15 May 2020
  3. Primary completion6 May 2021
  4. Study completion6 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Other
Time perspective
Prospective
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04351360
Sponsor's protocol ID
C19-26
Other IDs
2020-A00166-33
Acronym
CAF-ADCY5
Status last verified
Apr 2025
First submitted
13 Apr 2020
Last updated
4 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chen DH, Meneret A, Friedman JR, Korvatska O, Gad A, Bonkowski ES, Stessman HA, Doummar D, Mignot C, Anheim M, Bernes S, Davis MY, Damon-Perriere N, Degos B, Grabli D, Gras D, Hisama FM, Mackenzie KM, Swanson PD, Tranchant C, Vidailhet M, Winesett S, Trouillard O, Amendola LM, Dorschner MO, Weiss M, Eichler EE, Torkamani A, Roze E, Bird TD, Raskind WH. ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations. Neurology. 2015 Dec 8;85(23):2026-35. doi: 10.1212/WNL.0000000000002058. Epub 2015 Nov 4.

    PubMed 26537056

  • Friedman JR, Meneret A, Chen DH, Trouillard O, Vidailhet M, Raskind WH, Roze E. ADCY5 mutation carriers display pleiotropic paroxysmal day and nighttime dyskinesias. Mov Disord. 2016 Jan;31(1):147-8. doi: 10.1002/mds.26494. Epub 2015 Dec 21. No abstract available.

    PubMed 26686870

  • Lee KW, Hong JH, Choi IY, Che Y, Lee JK, Yang SD, Song CW, Kang HS, Lee JH, Noh JS, Shin HS, Han PL. Impaired D2 dopamine receptor function in mice lacking type 5 adenylyl cyclase. J Neurosci. 2002 Sep 15;22(18):7931-40. doi: 10.1523/JNEUROSCI.22-18-07931.2002.

    PubMed 12223546

  • Meneret A, Gras D, McGovern E, Roze E. Caffeine and the Dyskinesia Related to Mutations in the ADCY5 Gene. Ann Intern Med. 2019 Sep 17;171(6):439. doi: 10.7326/L19-0038. Epub 2019 Jun 11. No abstract available.

    PubMed 31181574

  • Vijiaratnam N, Newby R, Kempster PA. Depression and psychosis in ADCY5-related dyskinesia-part of the phenotypic spectrum? J Clin Neurosci. 2018 Nov;57:167-168. doi: 10.1016/j.jocn.2018.08.049. Epub 2018 Aug 30.

    PubMed 30172639

  • Yamada K, Kobayashi M, Kanda T. Involvement of adenosine A2A receptors in depression and anxiety. Int Rev Neurobiol. 2014;119:373-93. doi: 10.1016/B978-0-12-801022-8.00015-5.

    PubMed 25175973

  • Meneret A, Mohammad SS, Cif L, Doummar D, DeGusmao C, Anheim M, Barth M, Damier P, Demonceau N, Friedman J, Gallea C, Gras D, Gurgel-Giannetti J, Innes EA, Necpal J, Riant F, Sagnes S, Sarret C, Seliverstov Y, Paramanandam V, Shetty K, Tranchant C, Doulazmi M, Vidailhet M, Pringsheim T, Roze E. Efficacy of Caffeine in ADCY5-Related Dyskinesia: A Retrospective Study. Mov Disord. 2022 Jun;37(6):1294-1298. doi: 10.1002/mds.29006. Epub 2022 Apr 5.

    PubMed 35384065

Questions about this trial

What is this clinical trial studying?

An observational study of Dyskinesias, 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 4 inclusion and 0 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 4 Dec 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. 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?

Percentage of responders to caffeine (time frame: one hour). 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 NCT04351360, which also lists 7 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 4 Dec 2025.

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