Clinical trial NCT03368300: Epidemiology and Pathophysiology of Parkinsonism in the Caribbeans
Official title: Epidemiology and Pathophysiology of Parkinsonism in the Caribbeans
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Atypical Parkinsonism
Keywords: progressive supranuclear palsy
Caribbean atypical Parkinsonism
Annona Muricata
Lead sponsor: Centre Hospitalier Universitaire de la Guadeloupe
Sponsor class: OTHER
First posted: 2017-12-11
Enrollment: 550
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The primary aim of this study is to estimate the frequency and to characterize clinically atypical parkinsonism in the French West Indies and Guyana.

This study has been designed as epidemiological, multicentric transversal descriptive and longitudinal prospective study with biological collection and post-mortem neuropathological sub-study of brain tissue.
Primary purpose: OTHER

Brief summary: The primary aim of this study is to estimate the frequency and to characterize clinically atypical parkinsonism in the French West Indies and Guyana.

Detailed description: An atypical akineto-rigid parkinsonian syndrome, unresponsive to L-dopa has been evidenced in Guadeloupe. Abnormally frequent, this progressive supranuclear palsy (PSP)-like syndrome represents a new clinical entity. Unlike in classical PSP 70% of patients have myoclonus, 59% hallucinations, 78% REM sleep behavior disorders. Oculomotor pattern differs from classical PSP suggesting that cortical dysfunction predominates over brainstem impairments. Neuropathological examination in four patients has shown a widespread accumulation of the tau protein in the basal ganglia, the midbrain and cortical areas.

This syndrome has been associated to the regular consumption of food products derived from plants of the Annonaceae family, more specifically Annona Muricata (soursop), suggesting a toxic origin. We have already confirmed the neurotoxic potential of the lipophilic mitochondrial complex I inhibitor annonacin, the major acetogenin in Annona muricata. This class of compounds is specific to Annonaceae. Nanomolar concentrations of annonacin induce the death of dopaminergic neurons in culture, by impairment of energy production. Chronic systemic intoxication of rats with annonacin causes neuronal damage in the same brain regions that are damaged in patients with atypical parkinsonism. These results greatly suggest that the consumption of annonacea might contribute to the pathogenesis of the disease. The H1 subhaplotype in tau gene associated with PSP in Caucasians did not confer risk for PSP-like atypical parkinsonism in Guadeloupe.

Eligibility criteria: Inclusion Criteria:

* Pour les patients :

  1. Patient ou tiers responsable ayant reçu une information sur l'étude et ayant signé le consentement éclairé
  2. Patient âgé de plus de 18 ans
  3. Patient consultant en neurologie ou en gériatrie pour symptomatologie parkinsonienne ou pour troubles cognitifs évocateurs d'une démence à corps de Lewy
  4. Patient domicilié aux Antilles-Guyane

     Pour les témoins :
  5. Conjoint ou accompagnant ayant reçu une information sur l'étude et ayant signé le consentement éclairé
  6. Personne âgée de plus de 18 ans
  7. Personne ne présentant pas de pathologie d'allure neurodégénérative (Parkinson, démence notamment)
  8. Personne domiciliée aux Antilles-Guyane

Exclusion Criteria:

Pour les patients :

1. Syndrome parkinsonien secondaire (post-traumatique, vasculaire, iatrogène, post encéphalitique)
2. Patient non affilié au régime de sécurité sociale
3. En cas de difficulté de suivi le patient sera exclu de l'étude longitudinale

Pour les témoins :

1. Personnes présentant des troubles cognitifs ou un syndrome parkinsonien diagnostiqué.
2. Patient non affilié au régime de sécurité sociale -

Primary outcomes:
measure: to estimate the frequency and to characterize clinically atypical parkinsonism in the French West Indies and Guyana
timeFrame: At the end of the Period of inclusion, around 5-6 years
Secondary outcomes:
measure: to compare the proportion of atypical forms within parkinsonian syndromes;
timeFrame: At the end of the Period of inclusion, around 5-6 years
measure: to characterize the entity "Parkinson-dementia complex" described in Guadeloupe ; to characterize the entity "Parkinson-dementia complex" described in Guadeloupe ;
timeFrame: Through study completion, an average of 11 years
measure: to determine the natural history of typical and atypical forms of parkinsonism by following a cohort of the incident cases only;
timeFrame: Through study completion, an average of 11 years
measure: to determine the implication of a toxic alimentary factor in the etiopathogenesis of atypical forms and compare the results in the 3 areas (Guadeloupe, Guyane, Martinique);
timeFrame: Through study completion, an average of 11 years
measure: to determine the latency of cognitive decline in idiopathic Parkinson's disease in the 3 areas ;
timeFrame: Through study completion, an average of 11 years, post-mortem analysis after death if applicable
measure: to constitute a biological collection (plasma, DNA, serum).
timeFrame: At the end of the Period of inclusion, around 5-6 years
Other outcomes:
Locations:
city: Cayenne
country: French Guiana
facility: University Hospital of Guyana
city: Fort-de-France
country: Martinique
facility: University Hospital of Martinique
Study officials:
affiliation: University Hospital of Guadeloupe
name: Annie LANNUZEL, PU-PH
role: STUDY_DIRECTOR
affiliation: University Hospital of Martinique
name: Régine EDRAGAS, PH
role: PRINCIPAL_INVESTIGATOR
affiliation: : University Hospital of Guyana
name: Dominique MARNET, PH
role: PRINCIPAL_INVESTIGATOR
References: