Alzheimer DiseaseCHOLINENCT03090854
Cholinergic Markers Alzheimer's Disease
An observational study of Alzheimer Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- ADASCog
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 8 Nov 2017to 12 Jan 2021
- Phase
- Observational
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Mild to moderate Alzheimer disease 's patients
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Centre Mémoire de Ressources et de Recherche Paris Nord
Paris, 75010
About this study
Official title: 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.
Read the 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.
- Conditions
- Alzheimer Disease
- Being tested
- ADASCog
- Keywords
- Alzheimer's Disease, Cognition, Cholinergic target
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADASCogDiagnostic test
Neuropsychological test
| Study group | Role | What they receive |
|---|---|---|
| Alzheimer disease patients | Not described Receives: Diagnostic Test: ADASCog |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuropsychological test (ADASCog)
"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
Measured: between baseline and month 6
Secondary outcomes (3)
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
Alzheimer disease (AD)
Measured: month 6
Difference of CSF Ach AND AChE activity between responder and non responder groups
biological test
Measured: month 6
Statistical evaluation of the link between CSF Ach, AChE activity, total and phosphorylated Tau, Aß40 and Aß42.
biological test
Measured: month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study start8 Nov 2017
- Primary completion12 Jan 2021
- Study completion12 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03090854
- Sponsor's protocol ID
- K160402
- Other IDs
- 2016-AO1639-42
- Acronym
- CHOLINE
- Status last verified
- Feb 2021
- First submitted
- 20 Feb 2017
- Last updated
- 18 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholinergic Markers as Predictive Tools of Therapeutic Response in Alzheimer's Disease (CHOLINE)
- ClinicalTrials.gov ID
- NCT03090854
- Acronym / sponsor ID
- CHOLINE / K160402
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer's Disease, Cognition, Cholinergic target
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 8 Nov 2017 (actual)
- Primary completion
- 12 Jan 2021 (actual)
- Study completion
- 12 Jan 2021 (actual)
- First posted
- 27 Mar 2017 (actual)
- 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.
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.
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 design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alzheimer disease patients | – | Diagnostic Test: ADASCog |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Mild to moderate Alzheimer disease 's patients
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| ADASCogNeuropsychological test | Diagnostic test | Alzheimer disease patients |
Primary outcome
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
3 secondary outcomes
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
Difference of CSF Ach AND AChE activity between responder and non responder groups
Time frame: month 6
Statistical evaluation of the link between CSF Ach, AChE activity, total and phosphorylated Tau, Aß40 and Aß42.
Time frame: month 6
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2021.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer Disease, run by Assistance Publique - Hôpitaux de Paris 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 7 inclusion and 7 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: finished, as of the sponsor's last update on 18 Feb 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Neuropsychological test (ADASCog) (time frame: between baseline and month 6). 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 18 Feb 2021.