Cholinergic Markers Alzheimer's Disease (CHOLINE)
Cholinergic Markers as Predictive Tools of Therapeutic Response in Alzheimer's Disease (CHOLINE)
Several previous studies have assessed acetylcholine (Ach) and acetylcholinesterase activity (AchE-a) levels in Alzheimer's disease (AD) pathophysiology. The cerebrospinal fluid (CSF) Ach level was significantly decreased in AD patients, and correlated positively with dementia score and MMSE (1, 2). Two studies have demonstrated positive correlations between CSF AchE-a and CSF Tau, phosphorylated-Tau (P-Tau) and AB 1-42 peptide (3,4). ChEIs (cholinesterase inhibitors) have been approved for the treatment of AD but only 20 to 30 % of patients are responders (5). Any consistent data allow the clinician to predict the response to the treatment. The link between basal cholinergic status and ChEIs efficiency has never been done. Even if, there is a wild research in AD treatment, ChEIs or treatment acting on the Ach pathways will remain a long time valuable treatment particularly in moderate AD in which disease modifying therapies did not show any efficiency.
The investigators's objective is to prospectively explore the predicting value of CSF Ach and AchE-a levels on ChEIs response in AD patients.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
Strategy: Within the framework of the usual management, the investigators propose the protocol to patients who had an assay of the CSF biomarkers with a CSF AD biological profile before the introduction of an IChEs and having accepted Their CSF will stocked in our biobank. Patients will only have additional neuropsychological assessments. The rest of the care comes under the current care.
The quantification of ACh in the CSF will be performed in tandem mass spectrometry after separation by liquid chromatography (LC-MS / MS). AChE activity will be determined by colorimetric determination.
The investigators's objective is to prospectively explore the predicting value of CSF Ach and AchE-a levels on ChEIs response in AD patients.
The evaluation criteria will be
- Difference of the mean value of the ACh level and AChE activity in the CSF between the responder and non-respondier groups of patients.
- "Responder" patients are defined by an improvement of at least 4 points on the ADAS-Cog (cognitive part) ADAS-Cog after 6 months of treatment.
- "Non-responders" are defined as aggravation, lack of improvement or improvement <4 points on the ADAS-Cog scale.
Studientyp
Einschreibung (Tatsächlich)
Kontakte und Standorte
Studienorte
-
-
-
Paris, Frankreich, 75010
- Centre Mémoire de Ressources et de Recherche Paris Nord
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Probenahmeverfahren
Studienpopulation
Beschreibung
Inclusion Criteria:
Inclusion criteria :
- Male or Female aged ≥ 50 years
- Patients with a biological profile of CSF biomarkers in favor of Alzheimer's disease
- Alzheimer's disease diagnosed according to McKahnn 2011 criteria [1] at mild to moderate stage Clinical Dementia Rating (CDR) ≤2
- Indication to treatment with inhibitor of acetycholinesterase
- Patients benefiting from national health coverage
- Patients not subject to legal protection
- Fluent in French language
Exclusion criteria :
- No indication or contraindication to PL
- Contraindications to IChEs
- Patient included in other anti-Alzheimer drug clinical trial
- Clinical Dementia Rating CDR> 2
- Another cause of neurocognitive decline
- Serious psychiatric disorders
- Other serious life-threatening conditions
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
Kohorten und Interventionen
Gruppe / Kohorte |
Intervention / Behandlung |
|---|---|
|
Alzheimer disease patients
|
Neuropsychological test
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Neuropsychological test (ADASCog)
Zeitfenster: between baseline and month 6
|
"Responder" patients are defined by an improvement of at least 4 points on the ADAS-Cog (cognitive part) ADAS-Cog after 6 months of treatment.
"Non-responders" are defined as aggravation, lack of improvement or improvement <4 points on the ADAS-Cog scale
|
between baseline and month 6
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Rate of responder AD in this cohort included according to the new AD criteria and comparison of the current rate with the previous rate published using former AD criteria
Zeitfenster: month 6
|
Alzheimer disease (AD)
|
month 6
|
|
Difference of CSF Ach AND AChE activity between responder and non responder groups
Zeitfenster: month 6
|
biological test
|
month 6
|
|
Statistical evaluation of the link between CSF Ach, AChE activity, total and phosphorylated Tau, Aß40 and Aß42.
Zeitfenster: month 6
|
biological test
|
month 6
|
Mitarbeiter und Ermittler
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- K160402
- 2016-AO1639-42 (Andere Kennung: IDRCB)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .