Cohort Study to Identify Predictor Factors of Onset and Progression of Parkinson's Disease (ICEBERG)

Etude Des Facteurs prédictifs de l'Apparition et de l'évolution de la Maladie de Parkinson

Observational, prospective, monocentric study to assess clinical features, imaging and biologic biomarkers in Parkinson disease (PD) patients and rate of progression compared to healthy controls (HC) and subjects at risk to develop PD.

The primary objective of this study is to identify clinical, imaging and biologic markers of PD onset and progression for use in clinical trials of disease-modifying therapies.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Other: Clinical, biological and imaging followup

Detailed Description

ICEBERG will be a four-year natural history study of de novo idiopathic PD patients, healthy controls, and subjects at risk to develop PD (idiopathic Rem Behavior Disorder -iRBD, and probants of patients with PD genetically confirmed).

All subjects will be comprehensively assessed at baseline and every year thereafter. Subjects will undergo clinical (motor, neuropsychiatric, sleep, ocular and cognitive evaluations) and imaging assessments. Blood (including a DNA sample), stools, skin biopsy and cerebral spinal fluid (CSF) samples will be collected.

• Study Type: Observational
• Enrollment (Anticipated): 360

Contacts and Locations

• Study Contact: Name: Marie VIDAILHET, PhD; Email: marie.vidailhet@psl.aphp.fr

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Hôpital Pitié-Salpétrière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with recent onset of Parkinson Disease (less than 3 years since diagnosis) compared to subjects at risk to develop Parkinson Disease and healthy controls

Description

Inclusion Criteria:

• All subjects: Male or female age 18 years and older, MMSE score > 26, negative pregnancy test in potentially child-bearing women (contraindication to SPECT with DatScan).
• Idiopathic Parkinson disease subjects: diagnosis confirmed according to UK Parkinson's Disease Society Brain Bank criteria (UKPDSBB); disease duration less than 3 years.
• Genetic Parkinson disease subjects: parkinson diagnosis confirmed and mutation in parkin, LRRK2, SNCA or GBA genes.
• Prodromal subjects: subjects with identified relative with PD genetically confirmed or subjects with diagnosis of idiopathic Rem sleep Behavior Disorder (iRBD); neurological examination normal (no signs of parkinsonism).
• Healthy subjects: neurological examination normal

Exclusion Criteria:

• All subjects: Psychiatric disorder or any progressive life-threatening disease, impairment precluding appropriate information and instructions given concerning participation to the study; contra-indication to MRI or SPECT scan.
• Parkinson disease subjects: no dopamine transporter deficit at SPECT scan; parkinsonism induced by neuroleptics; neuroleptics intake within 6 months; atypical parkinson syndrom (MSA, PSP, CBD...)
• Parkinson disease subjects with mutation in Parkin, LRRK2, SNCA or GBA gene: atypical parkinson disease syndromes due to either drugs (e.g., metoclopramide, flunarizine, neuroleptics) or metabolic disorders (e.g., Wilson's disease), encephalitis or degenerative diseases (e.g., progressive supranuclear palsy) or currently taking neuroleptics or has taken neuroleptics within 6 months of baseline or any biological anomaly.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with an idiopathic Parkinson Disease,; Patients with recent onset of Parkinson Disease: N=200
Subjects at risk of PD; Subjects at risk to develop Parkinson Disease: subjects with idiopathic Rem-sleep behavior disorder (iRBD): N=50; subjects related to a patient with genetically confirmed Parkinson Disease: N=30	Other: Clinical, biological and imaging followup; Assessment of motor and non motor signs every 12 months. Imaging and blood, cerebral fluid, stools and skin samples for identification of biomarkers of disease phenotype and progression.
Controls; Healthy controls: N=50	Other: Clinical, biological and imaging followup; Assessment of motor and non motor signs every 12 months. Imaging and blood, cerebral fluid, stools and skin samples for identification of biomarkers of disease phenotype and progression.
Patients with Parkinson Disease with genetic mutation; Patients with Parkinson Disease with a genetic mutation in parkin, LRRK2, SNCA or GBA (N=30)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of change of clinical, imaging and biomic outcomes	Slopes of change of clinical, imaging and biomics compared between PD patients, subjects at risk to develop PD and healthy subjects. Identification of predictive factors of these rates of change. As examples, outcomes include: MDS-UPDRS, Mattis dementia rating scale, Non Motor Signs scale, DAT striatal uptake.	4 years (annual visits)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical milestones in PD patients	Occurence of complications such as falls, freezing, dyskinesias, motor fluctuations, cognitive impairment, dysautonomia. Identification of predictive factors of these complications. Rates of progression in sub-groups of patients defined by the presence of these complications.	4 years (annual visits)
Prodromal features in subjects at risk to develop PD	Prodromal features such as anosmia, dysautonomia, color vision impairment, will be evaluated at inclusion and during followup in subjects with iRBD or first-degree relatives of genetically confirmed PD patients. Frequency of these features will be compared between subjects who phenoconvert and those who don't. Relation between baseline DatSCAN binding and risk of phenoconversion will be analysed.	4 years (annual visits)
Phenoconversion in subjects at risk to develop PD	Phenoconversion is defined as occurence of an extrapyramidal syndrome, confirmed 12 months later. Exploratory analysis to determine whether rates of progression clinical, imaging and biomic markers may predict phenoconversion in groups of patients with iRBD or probants of patients with PD genetically confirmed.	4 years (annual visits)

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborators: IHU-A-ICM, Paris, France
• Investigators: Principal Investigator: Marie VIDAILHET, PhD, Assistance Publique - Hôpitaux de Paris, FRANCE; Study Chair: Jean-Christophe CORVOL, PhD, Assistance Publique - Hôpitaux de Paris, FRANCE

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2014
• Primary Completion (Anticipated): November 6, 2019
• Study Completion (Anticipated): November 6, 2024

Study Registration Dates

• First Submitted: October 10, 2014
• First Submitted That Met QC Criteria: December 1, 2014
• First Posted (Estimate): December 2, 2014

Study Record Updates

• Last Update Posted (Actual): December 7, 2017
• Last Update Submitted That Met QC Criteria: December 5, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Biomarkers; Parkinson Disease; Disease progression; Prognostic factors; Prodromal features
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: C13-74