ClinicalTrials.gov
ClinicalTrials.gov Menu

In Vivo Alzheimer Proteomics (PROMARA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02263235
Recruitment Status : Recruiting
First Posted : October 13, 2014
Last Update Posted : May 3, 2016
Sponsor:
Collaborators:
Assistance Publique - Hôpitaux de Paris
University Hospital, Clermont-Ferrand
International Atomic Energy Agency
Information provided by (Responsible Party):
University Hospital, Montpellier

September 18, 2014
October 13, 2014
May 3, 2016
June 2013
June 2017   (Final data collection date for primary outcome measure)
  • 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.
  • 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 %)
Same as current
Complete list of historical versions of study NCT02263235 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
In Vivo Alzheimer Proteomics
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
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.
Not Provided
Interventional
Not Applicable
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
  • Probable Alzheimer Disease
  • Parkinson Disease
  • Neurological Disease Without Cognitive Degradation
  • Brain Trauma
  • Acute Hydrocephaly
  • 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
  • Experimental: Group 1
    60 patients (20 probable AD, 20 Parkinson Disease (PK), 20 neurological disease without cognitive degradation)
    Intervention: Other: collection of CSF, blood, urine, saliva
  • Experimental: Group 2A
    20 patients (patients with brain trauma, acute hydrocephaly), with temporary derivation of the CSF
    Intervention: Biological: administration of stable isotope-labelled leucine-
  • Experimental: Group 2B
    30 patients (15 probable AD, 15 neurological disease without cognitive degradation)
    Intervention: Biological: administration of stable isotope-labelled leucine-
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
110
Same as current
June 2017
June 2017   (Final data collection date for primary outcome measure)

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..)
Sexes Eligible for Study: All
55 Years to 85 Years   (Adult, Senior)
No
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
France
 
 
NCT02263235
8652
No
Not Provided
Not Provided
University Hospital, Montpellier
University Hospital, Montpellier
  • Assistance Publique - Hôpitaux de Paris
  • University Hospital, Clermont-Ferrand
  • International Atomic Energy Agency
Principal Investigator: Sylvain Lehmann, PU-PH Laboratoire de Biochimie et Protéomique Clinique, IRMB St Eloi, CHRU de Montpellier
University Hospital, Montpellier
May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP