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In Vivo Alzheimer Proteomics (PROMARA)

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ClinicalTrials.gov Identifier: NCT02263235
Recruitment Status : Recruiting
First Posted : October 13, 2014
Last Update Posted : May 3, 2016
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief 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.

Condition or disease Intervention/treatment
Probable Alzheimer Disease Parkinson Disease Neurological Disease Without Cognitive Degradation Brain Trauma Acute Hydrocephaly Biological: administration of stable isotope-labelled leucine- Other: collection of CSF, blood, urine, saliva

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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
Study Start Date : June 2013
Estimated Primary Completion Date : June 2017
Estimated Study Completion Date : June 2017


Arms and Interventions

Arm Intervention/treatment
Experimental: Group 1
60 patients (20 probable AD, 20 Parkinson Disease (PK), 20 neurological disease without cognitive degradation)
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
Experimental: Group 2A
20 patients (patients with brain trauma, acute hydrocephaly), with temporary derivation of the CSF
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
Experimental: Group 2B
30 patients (15 probable AD, 15 neurological disease without cognitive degradation)
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


Outcome Measures

Primary Outcome Measures :
  1. C13 Leucine incorporation in Amyloid peptides (1-40, 1-42) at different time points (in %) [ Time Frame: 1.5 years ]
    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.

  2. C13 Leucine incorporation in detectable peptides generated after trypsin digestion of biological fluids from patients (CSF, blood, urine, saliva) (in %) [ Time Frame: 1.5 years ]
    C13 Leucine incorporation in detectable peptides generated after trypsin digestion of biological fluids from patients (CSF, blood, urine, saliva) (in %)


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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..)
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02263235


Contacts
Contact: Sylvain Lehmann, PU-PH +33 (0)4 67 33 71 23 s-lehmann@chu-montpellier.fr
Contact: Audrey Gabelle +33 (0)4 67 33 60 29 a-gabelle@chu-montpellier.fr

Locations
France
Laboratoire de Biochimie et Protéomique Clinique, CHU Montpellier Recruiting
Montpellier, France, 34295
Contact: Sylvain Lehmann, PU PH         
Contact: Audrey Gabelle         
Sub-Investigator: Audrey Gabelle         
Sponsors and Collaborators
University Hospital, Montpellier
Assistance Publique - Hôpitaux de Paris
University Hospital, Clermont-Ferrand
International Atomic Energy Agency
Investigators
Principal Investigator: Sylvain Lehmann, PU-PH Laboratoire de Biochimie et Protéomique Clinique, IRMB St Eloi, CHRU de Montpellier
More Information

Responsible Party: University Hospital, Montpellier
ClinicalTrials.gov Identifier: NCT02263235     History of Changes
Other Study ID Numbers: 8652
First Posted: October 13, 2014    Key Record Dates
Last Update Posted: May 3, 2016
Last Verified: May 2016

Keywords provided by University Hospital, Montpellier:
Alzheimer disease (AD)
diagnosis biomarkers
cerebrospinal fluid (CSF)
targeted quantitative proteomics
mass spectrometry
stable isotope-labelled leucine

Additional relevant MeSH terms:
Parkinson Disease
Alzheimer Disease
Nervous System Diseases
Brain Injuries, Traumatic
Hydrocephalus
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dementia
Tauopathies
Neurocognitive Disorders
Mental Disorders
Brain Injuries
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries