Trial to Evaluate the Ability of a Single Infusion of High-Density Lipoprotein (HDL) to Modulate Markers of Cerebral Ischaemia

Study Overview
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Brief Summary
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The plasma concentration of high-density lipoprotein (HDL) can have anti-inflammatory, anti-oxidative and anti-thrombotic effects in addition to being able to remove cholesterol from peripheral tissues for secretion via the liver. The investigators hypothesise that elevation of plasma HDLs will reduce the inflammatory response following removal of unstable atherosclerotic plaques in the carotid artery. Such plaques can cause strokes and there is great benefit from early surgical removal, however such surgical procedures involve significant risks to the patient. The investigators propose infusing HDL into patients prior to removal of their unstable carotid plaque and measuring the changes in inflammatory responses in comparison to a similar placebo controlled group of patients.

Detailed Description
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Following written informed consent, patients will be randomised to either the placebo or active arm of the study. Bloods will be taken for baseline measurements, and the infusion of either saline (placebo) or rHDL (active agent) will be carried out on the ward. Infusion will take 4 hours, and the active agent infused at 40mg/kg. Just prior to CAE, bloods will be collected (24 hours post-infusion) and the atherosclerotic tissue collected into RNA stabilising agent for subsequent analysis. Further bloods will then be collected 24 hours post-operatively (48 hours post-infusion). Patients vital signs will be monitored hourly following infusion and will be reviewed in out-patients at 6 weeks after the operation.

Official Title
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Does recHDL Given i.v. Before CEA Prevent Cerebral Ischaemia? - the Reveal Study.

Conditions
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Stroke

Intervention / Treatment
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* Drug: Reconstituted High Density Lipoprotein
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients listed for elective carotid endarterectomy Exclusion Criteria: pregnant women and women of childbearing age patient with impaired renal function or liver function patients sectioned under the Mental Health Act
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1.Saline Infusion<br>Patients randomised to this arm will receive an infusion of saline | Drug: Saline<br>* Saline (0.9%) is provided as a sterile infusion bag and infused over a period of 4 hours, 24 hours prior to carotid endarterectomy<br>* Other names: normal saline;|
| Active Comparator: 2.recHDL<br>Patients randomised to the active comparator arm of the study will receive 40mg/kg reconstituted High density lipoproteins (lot nos 05422-00006) over a period of 4 hours, 24 hours prior to carotid endarterectomy. | Drug: Reconstituted High Density Lipoprotein<br>* RecHDL (Lot Nos 05422-00006)is provided as a lyophilised powder and reconstituted with sterile water at 25 mg/ml. The infusion is made at 40 mg/kg over a period of 4 hours.<br>* Other names: discoidal HDL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory and thrombotic response |  | baseline, 24 hours after infusion, 48 hours after infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atherosclerosis, stroke, ischaemia