Choroid Plexus Dysfunction in Neurological Diseases

NCT06403189 | Recruiting

• 1 other identifier: APHP240013
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 2

Brief Summary

Cerebral folate deficiency (CFD), a partially treatable condition defined by a low folate cerebrospinal fluid (CSF) concentration, can be linked to genetic defects of folate metabolism or be secondary to various diseases without clear causal link. The team identified a neurological syndrome (named LHIPFOLFD) characterized by deep CFD and a specific leukoencephalopathy, related to several possible gene defects never involving folate metabolism. The team hypothesize that CFD in LHIPFOLD is due to a Choroid Plexus (CP) dysfunction, a brain organ that expresses transporters regulating flux between blood and CSF of numerous metabolites (including folate), and secretes CSF and specific proteins. Consequently, other potentially treatable biochemical abnormalities due to PC dysfunction may exist in LHIPFOLD, beyond CFD. Currently, there is no available clinical explorations to evaluate CP functions, whereas the team consider LHIPFOLD a very useful model to validate the capacity of some relevant diagnostic tools to do so. The objectives are to identify a CP-related MRI and biochemical signature in LHIPFOLD patients, using morphological and functional imaging (CP capillary permeability and CP macrovascular perfusion), and metabolomics/proteomics approaches (untargeted then targeted validation of candidate biomarkers related to CP physiology); and to set-up imaging and biochemical diagnostic tests for clinical practice. For this, brain MRI data and blood/CSF samples will be collected during 2 years from LHIPFOLD patients and controls. Some experimental data indicate that the innovative concept of generalized PC dysfunction as part of a more global pathophysiology has the potential to be applied to other neurological diseases like Alzheimer's disease. Therefore, efficient diagnostic tools exploring CP function will be of great utility not only in LHIPFOLD but also in more common neurological diseases, potentially leading to original therapeutic approaches.

Conditions

Plexus Choroideus; Metabolic Syndrome

Outcome Measures

Primary Outcomes (1)

• Identify a clinico-radio-proteo-metabolic profile indicative of choroid plexus dysfunction based on observation of LHIPFOLD patients as an experimental model.

  Characterization of a specific combined biochemical and radiological signature associated with choroid plexus damage observed in LHIPFOLD patients considered as "cases", comprising a limited number of biomarkers (target 5 to 6).

  37 months

Secondary Outcomes (3)

• Development of a simple diagnostic strategy based on biochemistry (metabolites/proteins) of blood and CSF discriminating choroid plexus alteration, using LHIPFOLD patients as an experimental model.

  37 months

• Development of a simple MRI diagnostic strategy (acquisition and analysis) that can be used routinely for the radiological identification of choroid plexus damage, based on the observation of LHIPFOLD patients as an experimental model.

  37 months

• Identification of therapeutic targets, i.e. blood and CSF biochemical biomarkers indicating choroid plexus dysfunction AND likely to be modulated by therapeutic intervention (e.g. supplementation of DFIC with folinic acid).

  37 months

Study Arms (1)

Population

OTHER

* LHIPFOLD patients * Patients with neurologic disease * healthy volunteers

Other: Biologic samples and MRI

Interventions

Biologic samples and MRI OTHER

* blood sample * lumbar punction * MRI

Population

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For LHIPFOLD patients:
• Suspicion of diagnosis or diagnosis of LHIPFOLD syndrome documented in the medical record, i.e. presence of these three manifestations: severe intrathecal deficiency in 5MTHF\< 10 nmol/L, hyperproteinorachia \> 1 g/L, and white matter abnormalities on cerebral MRI.
• Patient covered by Social Security or Complementary Health Insurance or any equivalent scheme (including AME).
• For Neurological Controls (NC) :
• No chronic pathology (notably no renal, cardiac, pulmonary or hepatic disease)
• Patients with one of the following neurological pathologies (confirmed diagnosis or strong suspicion), investigated in the course of routine clinical practice: Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, intracranial hypertension, normal pressure hydrocephalus, frontotemporal dementia.
• For Healthy Volunteers (VS):
• No chronic pathology (in particular, no renal, cardiac, pulmonary, hepatic or psychiatric disease)
• No history of neurological pathology
• No chronic alcohol intoxication
• No neurological or psychotropic medication.

You may not qualify if:

• For all research participants:
• Age \<18
• Pregnant and breast-feeding women.
• Participant unable to give informed consent.
• Participant with a contraindication to MRI: implantable cardiac defibrillators, prostheses, transdermal patches, catheters; implantable pumps; artificial heart valves; implants to treat deafness (if incompatible with MRI); surgical neurostimulator clips., pregnancy, extreme claustrophobia.
• Participants with contraindications to contrast injection: known allergy to gadolinium chelates, severe renal insufficiency, pregnancy (BHCG for women of childbearing age prior to MRI), breast-feeding.
• Participants with contraindications to LP: haemostasis abnormalities (PT\<50%, platelets \< 40\*109/L), mass syndrome on brain imaging, suspected infection at or near the needle insertion site, coagulopathy, cardiopulmonary insufficiency or respiratory distress.
• For NC and VS :
• Participant under legal protection (guardianship, curatorship)
• Participant not covered by Social Security or Complementary Health Insurance or any equivalent scheme (excluding AME).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

CIC Neurosciences

Paris, 75013, France

RECRUITING

Service de Neurologie, Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Central Study Contacts

Yann NADJAR, MD

CONTACT

01 42 16 17 52; yann.nadjar@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * consultation with a neurologist * Biologic samples (blood and lombar punction) * MRI

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: May 7, 2024
• Study Start: January 20, 2025
• Primary Completion (Estimated): February 3, 2028
• Study Completion (Estimated): February 3, 2028
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

FR (2)