Prognosis Biomarker of ADIRENNCT06825663
Marker of Brain Insulin Resistance in AD Prognosis
A study testing Blood punction in people with Prognosis Biomarker of AD and Mild Cognitive Impairment, run by Central Hospital, Nancy, France.
Trial summary
Basic research data from the literature on the links between cerebral insulin resistance and Alzheimer's disease (AD) suggest that this pathophysiological mechanism is involved at a very early stage in the development of the disease. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Prognosis Biomarker of AD, Mild Cognitive Impairment, Brain Insuline Resistance
- What is being tested?
- Blood punction
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- No sites listed yet
- Study dates
- 15 Mar 2025to 1 Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women aged 18 to 75
- Have been treated for mild cognitive impairment at the Nancy CHRU CMRR for 1 to 2 years
- Person affiliated to a social security scheme or beneficiary of such a scheme
- Person who has received full information on the organisation of the research and has signed an informed consent form
Who cannot join
- Adult subject to a legal protection measure (guardianship, curatorship, safeguard of justice)
- A person who has converted to clinically proven AD. The fact that an LP to measure AD markers has been performed is not a criterion for inclusion.
- An adult unable to give consent
- Person deprived of liberty by a judicial or administrative decision
- Persons under psychiatric care by virtue of articles L. 3212-1 and L. 3213-1.
- Pregnant women, women in labour or breastfeeding mothers
- Persons staying in a health or social establishment for purposes other than research.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Brain Insulin Resistance Index in Plasma Neuronal Exosomes As Predictive Biomarkers of Alzheimer's Disease
Basic research data from the literature on the links between cerebral insulin resistance and Alzheimer's disease (AD) suggest that this pathophysiological mechanism is involved at a very early stage in the development of the disease.
The insulin receptor (IR) is a tyrosine kinase receptor whose activation by insulin binding leads to autophosphorylation of its IRβ subunits and then of the insulin receptor substrate proteins (IRS-1). The ratio of IRS residues phosphorylated on serine 312 (P(Ser312)-IRS-1) to total phosphorylated IRS or IRS phosphorylated on its tyrosines has been proposed by some authors as an index of insulin resistance in the brain. IRS-1 proteins can be measured in exosomes, and in particular in neuronal exosomes isolated from plasma. It is therefore conceivable to measure this index in these biological samples specifically derived from neurons and available from a simple blood test, in order to determine whether it could be of prognostic interest in patients with mild cognitive impairment (MCI), in particular by making it possible to identify at an early stage patients who are going to convert to AD.
Read the detailed description
Basic research data from the literature on the links between cerebral insulin resistance and AD suggest that this pathophysiological mechanism is involved at a very early stage in the development of the disease. The multiple effects of insulin on cerebral bioenergetic regulation, synaptic viability, dendritic spine formation and neurotransmitter turnover, as well as on the clearance and degradation of Aβ peptide, All these factors suggest that dysregulation of insulin signalling pathways in the brain may contribute early on to neurodegeneration in AD, and represent both a therapeutic lever and a source of biomarkers relevant to diagnosis and prognosis (1). Several clinical trials are currently underway to validate the value of insulin administration or the use of drugs that affect insulin receptor sensitivity in the treatment of AD patients (2).
Given these arguments in favour of the role of cerebral insulin resistance in the early stages of AD, being able to measure such an index in plasma could prove invaluable in the management of patients. However, it is still difficult to distinguish between peripheral and central origin of the molecules measured, which explains the frequent use of lumbar puncture to diagnose neurological diseases. An alternative strategy could be based on the specific isolation of neuronal exosomes present in the blood. Exosomes are vesicles derived from late endosomes and containing nucleic acids, proteins and lipids. Specific protein markers, such as L1CAM for neurons, enable them to be isolated by immunoaffinity, according to their cellular origin. It is then possible to measure plasma biomarkers whose neuronal origin is certain (4).
IRS-1 proteins can be measured in exosomes, and in particular in neuronal exosomes isolated from plasma, but studies on the use of this index in AD are rare. One team of researchers has taken a particular interest in this question, showing that the insulin resistance index is significantly higher in AD patients than in control subjects or those with another neurodegenerative disease (3). A more recent study also showed that, in Alzheimer's subjects, brain volume was positively correlated with the level of IRS-1 phosphorylated on its tyrosine residues, whereas it was negatively correlated with the level of IRS-1 phosphorylated on serine 312 (5). This index in exosomes has also been proposed to distinguish good from poor responders to insulin treatment (6) or to illustrate the links between amyloid and Tau pathologies in AD (7). To date, no study has proposed using this index in plasma neuronal exosomes as a marker of conversion to AD in patients with mild cognitive impairment.
- Being tested
- Blood punction
- Keywords
- Alzheimer' disease, biomarker, Blood neuronal exosomes, Brain insuline resistance
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood punctionBiological
At each annual visit (+/- 3 months), 4X10 mL blood will be taken (1 dry tube, 1 heparinised tube, 2 EDTA tubes)
| Study group | Role | What they receive |
|---|---|---|
| MCI | Experimental | Men or women aged 18 to 75 followed for mild cognitive disorders at the Nancy CHRU CMRR for 1 to 2 years Receives: Biological: Blood punction |
What is being measured
The primary outcome is the main question the study is designed to answer.
prognostic performance of insulin resistance indexes
Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value of Pser312-IRS1/Ptyr-IRS1 and Pser312-IRS1/IRS1 ratios measured at t0 (inclusion visit) Threshold value for these ratios to predict conversion to AD to be defined (no thresholds for these ratios in the literature) Conversion to AD defined by the clinician according to usual practice
Measured: 3 years
Secondary outcomes (4)
prognostic performance of insulin resistance indexes in diabetic and non-diabetic MCI patients
Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value of Pser312-IRS1/Ptyr-IRS1 and Pser312-IRS1/IRS1 ratios measured at t0 (inclusion visit) Threshold value for these ratios to predict conversion to AD to be defined (no thresholds for these ratios in the literature) Conversion to AD defined by the clinician according to usual practice
Measured: 3 years
Link between cerebral insulin resistance index and conversion time
Time between date of first symptoms and date of conversion to AD in months Value of Pser312-IRS1/Ptyr-IRS1 and Pser312-IRS1/IRS1 ratios measured at t0 (inclusion visit) Conversion to AD defined by the clinician according to usual practice
Measured: 3 years
Link between cerebral insulin resistance index and glycated haemoglobin level
Pser312-IRS1/Ptyr-IRS1 and Pser312-IRS1/IRS1 ratios measured at t0 (inclusion visit) HbA1c in % measured at t0 (inclusion visit)
Measured: 3 years
Link between cerebral insulin resistance index and vascular resistance
Pser312-IRS1/Ptyr-IRS1 and Pser312-IRS1/IRS1 ratios measured at t0 (inclusion visit) Vascular resistance measured at t0 (inclusion visit)
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2025
- Study start15 Mar 2025 (estimated)
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prognosis Biomarker of ADStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 122 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Collaborators
- Thérèse Jonveaux, Laure Joly
- Responsible party
- Principal investigator, Catherine MALAPLATE, Central Hospital, Nancy, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06825663
- Sponsor's protocol ID
- 2024-A00609-38
- Acronym
- IREN
- Status last verified
- May 2024
- First submitted
- 10 Feb 2025
- Last updated
- 13 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Insulin Resistance Index in Plasma Neuronal Exosomes As Predictive Biomarkers of Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT06825663
- Acronym / sponsor ID
- IREN / 2024-A00609-38
- Keywords
- Alzheimer' disease, biomarker, Blood neuronal exosomes, Brain insuline resistance
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 122 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Collaborators
- Thérèse Jonveaux, Laure Joly
- Study start
- 15 Mar 2025 (estimated)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 13 Feb 2025 (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.
Basic research data from the literature on the links between cerebral insulin resistance and Alzheimer's disease (AD) suggest that this pathophysiological mechanism is involved at a very early stage in the development of the disease.
The insulin receptor (IR) is a tyrosine kinase receptor whose activation by insulin binding leads to autophosphorylation of its IRβ subunits and then of the insulin receptor substrate proteins (IRS-1). The ratio of IRS residues phosphorylated on serine 312 (P(Ser312)-IRS-1) to total phosphorylated IRS or IRS phosphorylated on its tyrosines has been proposed by some authors as an index of insulin resistance in the brain. IRS-1 proteins can be measured in exosomes, and in particular in neuronal exosomes isolated from plasma. It is therefore conceivable to measure this index in these biological samples specifically derived from neurons and available from a simple blood test, in order to determine whether it could be of prognostic interest in patients with mild cognitive impairment (MCI), in particular by making it possible to identify at an early stage patients who are going to convert to AD.
Detailed description
Basic research data from the literature on the links between cerebral insulin resistance and AD suggest that this pathophysiological mechanism is involved at a very early stage in the development of the disease. The multiple effects of insulin on cerebral bioenergetic regulation, synaptic viability, dendritic spine formation and neurotransmitter turnover, as well as on the clearance and degradation of Aβ peptide, All these factors suggest that dysregulation of insulin signalling pathways in the brain may contribute early on to neurodegeneration in AD, and represent both a therapeutic lever and a source of biomarkers relevant to diagnosis and prognosis (1). Several clinical trials are currently underway to validate the value of insulin administration or the use of drugs that affect insulin receptor sensitivity in the treatment of AD patients (2).
Given these arguments in favour of the role of cerebral insulin resistance in the early stages of AD, being able to measure such an index in plasma could prove invaluable in the management of patients. However, it is still difficult to distinguish between peripheral and central origin of the molecules measured, which explains the frequent use of lumbar puncture to diagnose neurological diseases. An alternative strategy could be based on the specific isolation of neuronal exosomes present in the blood. Exosomes are vesicles derived from late endosomes and containing nucleic acids, proteins and lipids. Specific protein markers, such as L1CAM for neurons, enable them to be isolated by immunoaffinity, according to their cellular origin. It is then possible to measure plasma biomarkers whose neuronal origin is certain (4).
IRS-1 proteins can be measured in exosomes, and in particular in neuronal exosomes isolated from plasma, but studies on the use of this index in AD are rare. One team of researchers has taken a particular interest in this question, showing that the insulin resistance index is significantly higher in AD patients than in control subjects or those with another neurodegenerative disease (3). A more recent study also showed that, in Alzheimer's subjects, brain volume was positively correlated with the level of IRS-1 phosphorylated on its tyrosine residues, whereas it was negatively correlated with the level of IRS-1 phosphorylated on serine 312 (5). This index in exosomes has also been proposed to distinguish good from poor responders to insulin treatment (6) or to illustrate the links between amyloid and Tau pathologies in AD (7). To date, no study has proposed using this index in plasma neuronal exosomes as a marker of conversion to AD in patients with mild cognitive impairment.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MCI | Experimental | Biological: Blood punctionMen or women aged 18 to 75 followed for mild cognitive disorders at the Nancy CHRU CMRR for 1 to 2 years |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men or women aged 18 to 75
- Have been treated for mild cognitive impairment at the Nancy CHRU CMRR for 1 to 2 years
- Person affiliated to a social security scheme or beneficiary of such a scheme
- Person who has received full information on the organisation of the research and has signed an informed consent form
Key exclusion criteria (7 listed)
- Adult subject to a legal protection measure (guardianship, curatorship, safeguard of justice)
- A person who has converted to clinically proven AD. The fact that an LP to measure AD markers has been performed is not a criterion for inclusion.
- An adult unable to give consent
- Person deprived of liberty by a judicial or administrative decision
- Persons under psychiatric care by virtue of articles L. 3212-1 and L. 3213-1.
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 |
|---|---|---|
| Blood punctionAt each annual visit (+/- 3 months), 4X10 mL blood will be taken (1 dry tube, 1 heparinised tube, 2 EDTA tubes) | Biological | MCI |
Primary outcome
prognostic performance of insulin resistance indexes
Time frame: 3 years
Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value of Pser312-IRS1/Ptyr-IRS1 and Pser312-IRS1/IRS1 ratios measured at t0 (inclusion visit) Threshold value for these ratios to predict conversion to AD to be defined (no thresholds for these ratios in the literature) Conversion to AD defined by the clinician according to usual practice
4 secondary outcomes
prognostic performance of insulin resistance indexes in diabetic and non-diabetic MCI patients
Time frame: 3 years
Link between cerebral insulin resistance index and conversion time
Time frame: 3 years
Link between cerebral insulin resistance index and glycated haemoglobin level
Time frame: 3 years
Link between cerebral insulin resistance index and vascular resistance
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2025.
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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.
Questions about this trial
What is this clinical trial studying?
A study testing Blood punction in people with Prognosis Biomarker of AD and Mild Cognitive Impairment, run by Central Hospital, Nancy, 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 4 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: opening soon, as of the sponsor's last update on 13 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Catherine Malaplate, PhD,PharmD (00 33 (0)3 83 15 55 13, c.malaplate@chru-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
prognostic performance of insulin resistance indexes (time frame: 3 years). 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 13 Feb 2025.