In Vivo Alzheimer Proteomics

Parkinson Disease Clinical Trial

— PROMARA  

Official title:

Use of Targeted Quantitative Proteomics and Metabolic Labelling With Stable Isotopes for the Diagnosis and the Investigation of Neurological Disorders and in Particular Alzheimer Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02263235
• Other study ID #: 8652
• Status: Terminated
• Phase: N/A
• Start date: October 8, 2013
• Est. completion date: May 22, 2018

Study information

• Verified date: December 2021
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In France, an estimated 860 000 patients are affected by Alzheimer Disease (AD) which represents, as in other developed countries, a major public health issue. In many cases, AD diagnosis is uncertain and its clinical evolution unpredictable. The exactitude of the diagnosis is however particularly important in the perspective of the validation and use of new therapeutic strategies in AD. Detection of cerebrospinal fluid (CSF) diagnosis biomarkers fell short in the detection, of atypical/mixed cases, of some differential diagnosis, and in differentiating rapid or slow clinical evolutions. Hence, CSF analysis gives a unique opportunity to detect and validate biomarkers in many neurological disorders. Nevertheless, in medical practice, CSF biological analysis is currently limited to a small number of analytes.Quantitative and targeted mass spectrometry, especially operated in the Multiple reaction monitoring mode (MRM), represents an alternative to immunodetection and could be used to detect specific biomarkers in complex matrices such as plasma by specifically discriminating the proteotypic peptides corresponding to each proteins. Mass spectrometry has also the ability to distinguish and quantify isotopically labelled and unlabeled selected targets. This ability was used in a publication by the group of R. Bateman (Washington University, St Louis, USA) who could, after administering stable isotope-labelled leucine, evaluate Ab synthesis and clearance in humans. This approach has an enormous potential to study the metabolism of proteins within the human CNS and consequently help in the understanding and diagnosis of neurological disorders.The main objective of this program is set up a targeted quantitative mass spectrometry method for existing and stable isotope-labelled CSF biomarkers in the neurological field; exploit this approach for diagnostic purpurses and to gain knowledge in the pathophysiology of diseases.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 89
• Est. completion date: May 22, 2018
• Est. primary completion date: May 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

Inclusion Criteria:

• Reports written consent, informed and signed by the patient and a trusted person

• Subject member or beneficiary of a social security system

Specific criteria for group 1 and 2B :

• Age between 55 and 85 years old for patients

• Subject with AD or other neurodegenerative disease (frontotemporal dementia, dementia with Lewy bodies, Parkinson disease)

• Subjects with chronic adult hydrocephalus (HCA) requiring depletion lumbar puncture (PL)

Specific criteria for group 2A :

• Adult patient requiring neurosurgery with CSF shunt (subject with brain trauma, acute hydrocephaly) and favorable evolution that allows removal of the shunt

Exclusion Criteria:

• Patient deprived of liberty by judicial or administrative decision

• Major protected by law

• Pregnancy, women of childbearing age with risk of pregnancy, or breast-feeding

• Presence of a transmissible viral disease (HlV, hepatitis B and C)

• Patient included in a clinical trial

• lnadequate cardiac, hepatic or severe renal disfunction

• Disease amino acid metabolism (Leucinose..)

Exclusion Criteria:

• Information clinical and para-clinical insufficient or unavailable

• Patient deprived of liberty by judicial or administrative decision

• Major protected by law

• Pregnancy, women of childbearing age with risk of pregnancy, or breast

• feeding

• Presence of a transmissible viral disease (HIV, hepatitis B and C)

• Patient included in a clinical trial

• Patient exclusion period relative to another protocol or for which the maximum annual compensation of 4500€ has been reached

• Inadequate cardiac, hepatic or severe renal

• Disease amino acid metabolism (Leucinose..)

Related Conditions & MeSH terms

• Acute Hydrocephaly
• Alzheimer Disease
• Brain Injuries, Traumatic
• Brain Trauma
• Hydrocephalus
• Nervous System Diseases
• Neurological Disease Without Cognitive Degradation
• Parkinson Disease
• Probable Alzheimer Disease

Intervention

Biological:
• administration of stable isotope-labelled leucine-
- administration of stable isotope-labelled leucine : by drip, for group 2A and group 2B. Group 1 (control group) : 1 collection of CSF. Group 2B : 4 collections of CSF, 24 hours after administration of stable isotope-labelled leucin. Group 2A (patients with brain trauma, acute hydrocephaly) : continuous collection of CSF, for 24 to 36 hours

Other:
• collection of CSF, blood, urine, saliva
- administration of stable isotope-labelled leucine : by drip, for group 2A and group 2B. Group 1 (control group) : 1 collection of CSF. Group 2B : 4 collections of CSF, 24 hours after administration of stable isotope-labelled leucin. Group 2A (patients with brain trauma, acute hydrocephaly) : continuous collection of CSF, for 24 to 36 hours

Locations

Country	Name	City	State
France	Laboratoire de Biochimie et Protéomique Clinique, CHU Montpellier	Montpellier

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Montpellier	Assistance Publique - Hôpitaux de Paris, International Atomic Energy Agency, University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	C13 Leucine incorporation in Amyloid peptides (1-40, 1-42) at different time points (in %)	Analysis of labelled samples with mass spectrometry. Data generated will be studied to validate the experimental model and understand the pathophysiology of neurological disorders. A collection of labelled biological samples will also be generated.	1.5 years
Primary	C13 Leucine incorporation in detectable peptides generated after trypsin digestion of biological fluids from patients (CSF, blood, urine, saliva) (in %)	C13 Leucine incorporation in detectable peptides generated after trypsin digestion of biological fluids from patients (CSF, blood, urine, saliva) (in %)	1.5 years