Probable Alzheimer DiseasePROMARANCT02263235
In Vivo Alzheimer Proteomics
A study testing administration of stable isotope-labelled leucine- and collection of CSF, blood, urine, saliva in people with Probable Alzheimer Disease and Parkinson Disease, run by University Hospital, Montpellier at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Probable Alzheimer Disease, Parkinson Disease, Neurological Disease Without Cognitive Degradation
- What is being tested?
- administration of stable isotope-labelled leucine- and collection of CSF, blood, urine, saliva
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 89 participants
- Where
- 1 siteFrance
- Study dates
- 8 Oct 2013to 22 May 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- Disease amino acid metabolism (Leucinose..)
- 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..)
Trial locations and contacts
1 site in 1 country.
France1 site
Laboratoire de Biochimie et Protéomique Clinique, CHU Montpellier
Montpellier, 34295
About this study
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
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.
- Conditions
- Probable Alzheimer Disease, Parkinson Disease, Neurological Disease Without Cognitive Degradation, Brain Trauma, Acute Hydrocephaly
- Being tested
- administration of stable isotope-labelled leucine-, collection of CSF, blood, urine, saliva
- Keywords
- Alzheimer disease (AD), diagnosis biomarkers, cerebrospinal fluid (CSF), targeted quantitative proteomics, mass spectrometry, stable isotope-labelled leucine
- Medical subject headings
- Parkinson Disease, Brain Injuries, Traumatic, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
administration of stable isotope-labelled leucine-Biological
- 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
collection of CSF, blood, urine, salivaOther
- 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
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | 60 patients (20 probable AD, 20 Parkinson Disease (PK), 20 neurological disease without cognitive degradation) Receives: Other: collection of CSF, blood, urine, saliva |
| Group 2A | Experimental | 20 patients (patients with brain trauma, acute hydrocephaly), with temporary derivation of the CSF Receives: Biological: administration of stable isotope-labelled leucine- |
| Group 2B | Experimental | 30 patients (15 probable AD, 15 neurological disease without cognitive degradation) Receives: Biological: administration of stable isotope-labelled leucine- |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1.5 years
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 %)
Measured: 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2014 (estimated)
- Study start8 Oct 2013
- Primary completion22 May 2018
- Study completion22 May 2018
Why it stopped: end of the inclusion period
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Probable Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Collaborators
- Assistance Publique - Hôpitaux de Paris, University Hospital, Clermont-Ferrand, International Atomic Energy Agency
- Responsible party
- Sponsor
- Investigators
- Sylvain Lehmann, PU-PH, Principal investigator, Laboratoire de Biochimie et Protéomique Clinique, IRMB St Eloi, CHRU de Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02263235
- Sponsor's protocol ID
- 8652
- Acronym
- PROMARA
- Status last verified
- Dec 2021
- First submitted
- 18 Sep 2014
- Last updated
- 28 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02263235
- Acronym / sponsor ID
- PROMARA / 8652
- Conditions
- Probable Alzheimer Disease, Parkinson Disease, Neurological Disease Without Cognitive Degradation, Brain Trauma, Acute Hydrocephaly
- Keywords
- Alzheimer disease (AD), diagnosis biomarkers, cerebrospinal fluid (CSF), targeted quantitative proteomics, mass spectrometry, stable isotope-labelled leucine
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: end of the inclusion period
- Enrolment
- 89 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Collaborators
- Assistance Publique - Hôpitaux de Paris, University Hospital, Clermont-Ferrand, International Atomic Energy Agency
- Study start
- 8 Oct 2013 (actual)
- Primary completion
- 22 May 2018 (actual)
- Study completion
- 22 May 2018 (actual)
- First posted
- 13 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Other: collection of CSF, blood, urine, saliva60 patients (20 probable AD, 20 Parkinson Disease (PK), 20 neurological disease without cognitive degradation) |
| Group 2A | Experimental | Biological: administration of stable isotope-labelled leucine-20 patients (patients with brain trauma, acute hydrocephaly), with temporary derivation of the CSF |
| Group 2B | Experimental | Biological: administration of stable isotope-labelled leucine-30 patients (15 probable AD, 15 neurological disease without cognitive degradation) |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Reports written consent, informed and signed by the patient and a trusted person
- Subject member or beneficiary of a social security system
- 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)
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Biological | Group 2A, Group 2B |
| 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 | Other | Group 1 |
Primary outcome
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 %)
Results and safety
The study was stopped early (reason given: end of the inclusion period). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sylvain Lehmann, PU-PH principal investigator
Laboratoire de Biochimie et Protéomique Clinique, IRMB St Eloi, CHRU de Montpellier
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing administration of stable isotope-labelled leucine- and collection of CSF, blood, urine, saliva in people with Probable Alzheimer Disease and Parkinson Disease, run by University Hospital, Montpellier at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: end of the inclusion period). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
C13 Leucine incorporation in Amyloid peptides (1-40, 1-42) at different time points (in %) (time frame: 1.5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2021.