Study for the Early Diagnosis of Parkinson's Disease

PDx Biomarker Assay Study for the Diagnosis of Parkinson's Disease

The main objective of the study is to design and validate the blood based PDx gene expression and miRNA assay for the early diagnosis of Parkinson's disease patients. Differential diagnosis includes patients with Multiple System Atrophy, Progressive Supranuclear Palsy, Corticobasal Degeneration, Lewy Body Dementia, Essential Tremor and Normal Controls.

Study Overview

• Status: Unknown
• Conditions: Parkinson's Disease, Idiopathic

Detailed Description

In this study, the PDx assay will be designed and validated in order to distinguish between Idiopathic Parkinson's disease (PD) to patients with similar symptoms and healthy controls. The differential diagnosis cohort includes patients diagnosed with Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), Essential Tremor (ET) or Lewy Body Dementia (LBD) and Healthy Controls.

This is a prospective observational study. Blood samples and clinical data will be collected at the first and only study visit. The expression levels of 5 to 6 genes will be analyzed by blinding technicians concerning the diagnosis, demographic data and clinical data, which will be revealed after sending PDx gene expression values to the clinical sites. The gene expression levels will be compared between Parkinson's disease patients to the differential diagnosis cohort and healthy controls. Additional mRNA and miRNA markers will be explored. The primary aim of the study is to design and validate a clinical classifier that will aid the physician in the diagnosis of Parkinson's disease patients. The analysis will be performed in two stages: Stage 1) Exploration analysis and Stage 2) Validation. After one year of taking a blood sample, the study physician will contacted to confirm the patient's diagnosis.

Blood samples will be collected at specialized movement disorder clinics.

Medical history, clinical diagnostic features, family history in regard to Parkinson's disease, use of medication and routine imaging assessment (not mandatory) will be collected at the first and only patient visit.

• Study Type: Observational
• Enrollment (Actual): 410

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 31096,
    • Rambam Health Care Campus
  • Petach Tikvah, Israel, 4941492
    • Rabin Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Tel HaShomer, Israel, 52621
    • Chaim Sheba Medical Center
  • Tsrifin, Israel, 70300
    • Assaf Harofeh Medical Center
• Italy
  • Pisa, Italy, 56126
    • Pisa University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Movement disorder clinics

Description

Inclusion Criteria:

• Patient is able and willing to read the informed consent form
• Patient with clinical diagnosis of Idiopathic Parkinson's Disease according to Queen Square Brain Bank Criteria up to one year prior to enrollment in study
• Patient with diagnosis of MSA, PSP, CBD, Lewy Body Dementia, Essential Tremor or Healthy Control
• Men and Women aged 40-80 years
• Willing and able to comply with procurement of blood sample

Exclusion Criteria:

• Any medical, psychiatric or other conditions which, in the opinion of the investigator, would preclude participation
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Idiopathic Parkinson's disease; Patient with clinical diagnosis of Idiopathic Parkinson's Disease according to Queen Square Brain Bank Criteria up to one year prior to enrollment in study.
Differential Diagnosis Group; MSA, PSP, CBD, Lewy body dementia, Essential Tremor, and Healthy Controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Diagnostic Accuracy of PDx mRNA Assay in Diagnosing Idiopathic Parkinson's Disease	Investigate the diagnostic accuracy of the PDx gene expression assay, comprised of 5-6 expressed genes (mRNA - RQ-PCR), to differentiate patients with Idiopathic Parkinson's disease from the Differential Diagnosis Group. Diagnostic Accuracy includes sensitivity, specificity, likelihood ratios and the area under the receiver operating characteristic (ROC) curve. Diagnostic Accuracy will be calculated by comparing the PDx assay results to the Gold Standard Diagnosis, which will be the Clinical diagnosis of the Patient one year after the first and only visit (day of blood collection). The physician investigator will be contacted if there was any change in the baseline diagnosis one year after blood collection according to routine clinical findings.	One year from enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Accuracy of each one of the PDx assay's expressed genes for Differentiating Idiopathic Parkinson's Disease Patients from Atypical Parkinsonism Patients.	Investigate the diagnostic accuracy (sensitivity, specificity, likelihood ratios and AUC) of each one of the PDx assay expressed genes (RQ-PCR) to differentiate Idiopathic Parkinson's Disease Patients from Atypical Parkinsonism Patients.	One year from enrollment
Diagnostic Accuracy of each one of the PDx assay's expressed genes for Differentiating Idiopathic Parkinson's Disease Patients from Essential Tremor Patients.	Investigate the diagnostic accuracy (sensitivity, specificity, likelihood ratios and AUC) of each one of the PDx assay expressed genes (RQ-PCR) to differentiate Idiopathic Parkinson's Disease Patients from Essential Tremor Patients.	One year from enrollment
Diagnostic Accuracy of each one of the PDx assay's expressed genes for Differentiating Idiopathic Parkinson's Disease Patients from Healthy Controls.	Investigate the diagnostic accuracy (sensitivity, specificity, likelihood ratios and AUC) of each one of the PDx assay expressed genes (RQ-PCR) to differentiate Idiopathic Parkinson's Disease Patients from Healthy Controls.	One year from enrollment

Collaborators and Investigators

• Sponsor: Bio Shai Ltd.
• Investigators: Principal Investigator: Ofer Gonen, MD, Assaf-Harofeh Medical Center

Publications and helpful links

General Publications

• Berardelli A, Wenning GK, Antonini A, Berg D, Bloem BR, Bonifati V, Brooks D, Burn DJ, Colosimo C, Fanciulli A, Ferreira J, Gasser T, Grandas F, Kanovsky P, Kostic V, Kulisevsky J, Oertel W, Poewe W, Reese JP, Relja M, Ruzicka E, Schrag A, Seppi K, Taba P, Vidailhet M. EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease. Eur J Neurol. 2013 Jan;20(1):16-34. doi: 10.1111/ene.12022. Erratum In: Eur J Neurol. 2013 Feb;20(2):406.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (ANTICIPATED): December 1, 2019
• Study Completion (ANTICIPATED): December 1, 2019

Study Registration Dates

• First Submitted: October 27, 2014
• First Submitted That Met QC Criteria: November 2, 2014
• First Posted (ESTIMATE): November 5, 2014

Study Record Updates

• Last Update Posted (ACTUAL): July 10, 2018
• Last Update Submitted That Met QC Criteria: July 9, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Diagnosis
• 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: PDx001; 82/14 (OTHER: Assaf HaRofeh); TASMC -14-TG-0489-14-TLV-CTIL (OTHER: Tel Aviv Sourasky Medical Center); 1735-14-SMC (OTHER: Sheba Medical Center); 0463-14-RMB (OTHER: Rambam Health Care Campus)