Study of the Pathophysiological Mechanisms Involved in Bleeding Events (LOWE)

November 17, 2025 updated by: Assistance Publique - Hôpitaux de Paris

Study of the Pathophysiological Mechanisms Involved in Bleeding Events Observed in Patients With Lowe Syndrome

Lowe syndrome is associated with mutations in the OCRL1 gene, which encodes OCRL1, a phosphatidylinositol-4, 5-bisphosphate (PtdIns(4, 5)P (2))5-phosphatase. PtdIns(4, 5)P2, a substrate of OCRL1, is an important signaling molecule within the cell. An abnormal rate of hemorrhagic events was found in a retrospective clinical survey, suggesting platelet dysfunction.

The main objective of the study is to confirm the presence of platelet dysfunction in Lowe syndrome and to characterize this abnormality.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Introduction: Lowe syndrome (LS), also known as oculocerebrorenal syndrome of Lowe (OCRL), is a rare X-linked condition characterized by congenital cataracts, defective renal tubule cell function, muscular hypotonia and variable degrees of mental retardation. Patients with LS require frequent surgery, some of which are associated with a severe haemorrhagic risk, such as scoliosis reduction, hip surgery, or eye surgery. In a recent retrospective clinical survey of French LS patients, we observed an abnormal rate of haemorrhagic events, some of which had dramatic outcomes. LS is caused BYMUTATIONS in the OCRL gene, which encodes OCRL, an inositol polyphosphate 5-phosphatase. The preferred OCRLsubstrate is the membrane phospholipid phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2). OCRL also contains a Rho GTPase-activating protein(GAP)-like domain that participates in the regulation of Rho proteins (Rho, Rac, Cdc42), as GTPase-activating proteins or by mediating in protein-protein interactions. PtdIns(4,5)P2 and Rho-dependent signalling play a central role in many important cellular processes, including vesicular trafficking and cytoskeletal organization both of which are very important for platelet function. Thus, modulation of PtdIns(4,5)P2 levels and/or Rho-dependent signalling would be expected to impact platelet function.

Based on the clinical observation, we tested whether hemorrhagic symptom of 6 Lowe patients could be related to homeostasis abnormalities and we found that all the six patients had a prolonged closure time tested by PFA100 analyzer (Platelet Function Analyzer). These results were measured in absence of interfering factor such anemia, thrombopenia, or von Willebrand factor deficiency, thus suggesting platelet dysfunction.

Study justification:

The comprehension of the physiopathology implicated in the abnormal hemorrhagic risk is of major interest in term of prevention and clinical management in Lowe patients who requires frequent surgical care.

Objectives:

The main objective of the study is to confirm the presence of platelet dysfunction in Lowe syndrome and to characterize this abnormality. The secondary aims are to settle a functional test allowing the detection of patients with increasing hemorrhagic risk. Moreover, we could determinate whether platelet is an interesting cellular model, easily available, for further OCRL1 studies in Lowe patients.

Methods:

We will investigate platelet activation response in 15 Lowe cases and 15 normal cases. The evaluation criteria will include the PFA100, THROMBOELASTOMETRY (ROTEM), aggregation, secretion, adhesion in a flux system and clot retraction. We will also compare molecular (phospho-proteins, phospholipid...) and structural modifications of the non activated platelet and of activating platelet.

Conclusion:

The characterization of a platelet activation abnormality in Lowe patients could lead to major benefit for the patients with systematic homeostasis screening and special precautions rules before surgery, often required in this multisystemic condition. Moreover, this study could contribute to go further into PI(4,5)P2 signaling pathways and may provide clues to the interrelationship between these processes in normal metabolism and diseases states.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75015
        • Necker Enfants Malades Hospital, Genetic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 45 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Patient with a clinical syndrome of Lowe (congenital cataracts, renal tubular dysfunction and neuromuscular damage) with a molecular defect in the gene known OCRL1.
  • For the centre of Necker, patients should have a weight> 10 kg. For the centre of Toulouse site, patients should have a weight> 40 kg.
  • No alteration of glomerular function (creatinine clearance> 30 ml/min/1.73m ²)
  • No significant anemia (hematocrit> 25%, hemoglobin> 8 g / L)
  • Every patient should have included a signed informed consent. For minor patients, the consent of parents or legal guardian must be obtained.
  • Patients may be included only if they receive social security coverage or CMU

Exclusion Criteria:

  • Weight less than 10 kg for the centre of Necker
  • Weight less than 40 kg for the centre of Toulouse
  • Major renal insufficiency (creatinine clearance <30 ml/min/1.73m ²)
  • Profound anemia (hematocrit <25%, Hb <8g/dl)
  • Patients taking drugs interfering with hemostasis in the eight days before the survey
  • Patients with major behavior disorder making it difficult to achieve the blood sample, despite the nitrous oxide
  • Patients with a other pathology of hemostasis (hemophilia, thrombotic disease)
  • Participation in another clinical study requiring a blood sample within 4 weeks
  • Contraindication to EMLA patch: confers Summary of Product Characteristics.
  • Contraindication to KALINOX: confers Summary of Product Characteristics.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
experimental
Other: Blood sample
Blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The platelet function will be evaluated by comparing the intensity of platelet responses obtained in patient and controls
Time Frame: 18 months

The platelet function will be evaluated by comparing the intensity of platelet responses obtained in patient and controls. Various platelet responses will be studied:

  • The measurement of platelet closure time by PFA100
  • Aggregation, retraction, secretion and adhesion
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterization of abnormalities in platelet-signalling pathways
Time Frame: 18 months
Characterization of abnormalities in platelet-signalling pathways
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

URC-CIC Paris Descartes Necker Cochin

Investigators

  • Principal Investigator: Geneviève Baujat, MD, PhD, Hôpital Necker Enfants Malades, Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (Actual)

July 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

March 11, 2011

First Submitted That Met QC Criteria

March 11, 2011

First Posted (Estimated)

March 14, 2011

Study Record Updates

Last Update Posted (Actual)

November 20, 2025

Last Update Submitted That Met QC Criteria

November 17, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P071008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Oculocerebrorenal Syndrome

Clinical Trials on Blood sample

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Thailand

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe