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Cholinergic Markers Alzheimer's Disease (CHOLINE)

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ClinicalTrials.gov Identifier: NCT03090854
Recruitment Status : Not yet recruiting
First Posted : March 27, 2017
Last Update Posted : August 29, 2017
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

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.


Condition or disease Intervention/treatment
Alzheimer Disease Diagnostic Test: ADASCog

Detailed Description:

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.

Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Cholinergic Markers as Predictive Tools of Therapeutic Response in Alzheimer's Disease (CHOLINE)
Estimated Study Start Date : September 1, 2017
Estimated Primary Completion Date : September 1, 2019
Estimated Study Completion Date : September 1, 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Alzheimer disease patients Diagnostic Test: ADASCog
Neuropsychological test




Primary Outcome Measures :
  1. Neuropsychological test (ADASCog) [ Time Frame: 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


Secondary Outcome Measures :
  1. 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 [ Time Frame: month 6 ]
    Alzheimer disease (AD)

  2. Difference of CSF Ach AND AChE activity between responder and non responder groups [ Time Frame: month 6 ]
    biological test

  3. Statistical evaluation of the link between CSF Ach, AChE activity, total and phosphorylated Tau, Aß40 and Aß42. [ Time Frame: month 6 ]
    biological test



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Mild to moderate Alzheimer disease 's patients
Criteria

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

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): NCT03090854


Contacts
Contact: Claire PAQUET, MD, PhD 33 6 84 18 28 34 claire.paquet@inserm.fr

Locations
France
Centre Mémoire de Ressources et de Recherche Paris Nord Not yet recruiting
Paris, France, 75010
Contact: Claire PAQUET, MD, PhD    33 6 84 18 28 34    claire.paquet@inserm.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03090854     History of Changes
Other Study ID Numbers: K160402
2016-AO1639-42 ( Other Identifier: IDRCB )
First Posted: March 27, 2017    Key Record Dates
Last Update Posted: August 29, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Alzheimer's Disease
Cognition
Cholinergic target

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Dementia
Tauopathies
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs