Inhibiting HDAC9 as a novel treatment for large artery atherosclerotic stroke: a pilot study
Stroke
Subjects with symptomatic carotid stenosis causing stroke or TIA are split equally into two groups: the sodium valproate group and the control group (no treatment). Study participants randomly allocated to the treatment group will take Sodium valproate 200 mg twice a day for the first 2 weeks and then 400 mg twice a day for the remaining 2 years. Study participants randomly allocated to the control group will not take sodium valproate. At baseline and at 3 months, subjects will undergo clinical assessment, neurological and cardiovascular examination, CT angiogram, PET/CT of the carotids, and an MR of the carotids. In addition, at 2 years subjects will undergo clinical assessment, neurological and cardiovascular examination, and CT angiogram. Screening (Baseline visit only). During routine clinical care consultations, patients will be approached by their clinical team if they are felt to be appropriate for the project. The suitability of participants will be assessed against the inclusion and exclusion criteria. Those who are eligible will be provided with a participant information sheet (PIS) and the study will be explained by a trained researcher. The participant will then be asked to consent to participate in the study by completing a consent form. They will be given a copy of the consent and PIS to take away. Blood collection. All participants who have not had their renal function measured will have a blood sample taken to calculate their renal function. If this is below an acceptable level (an eGFR =<30 ml/min/1.73m²) they will not be able to be a part of the study. Creatinine and liver function tests will also be performed if not done in the last three months. All subjects who are eligible and who have consented will be contacted to book a baseline visit. Randomisation: Prior to, or on the day of, the baseline visit, participants will be randomly allocated (1:1) to the treatment group or to the control group using a web-based randomisation system. Particip
Current participant inclusion criteria as of 15/06/2021: 1. Have given written informed consent to participate 2. Be aged 50 years and over 3. Have had a recent (less than 6 months) symptomatic carotid atherosclerotic stroke or transient ischaemic attack (TIA) with carotid stenosis of 30-99%. This will be determined from clinical imaging such as US Duplex/ultrasound, CT Angiogram or MR Angiogram. The percentage of stenosis will be measured using NASCET criteria* *Patients with tight carotid stenosis (> 70%) will usually be offered carotid endarterectomy and therefore would not be suitable for the study. However many patients present with moderate carotid stenosis (30–70%) and do not receive carotid endarterectomy. Therefore we would anticipate that the majority of our patients will have this degree of stenosis (30-70%). In a recent observational study of PET in acute symptomatic carotid stenosis (ICARUSS, co-ordinated by Dr Nick Evans) approximately two thirds of all patients with carotid stenosis did not progress to endarterectomy and therefore we feel it is feasible to recruit this number of patients. Previous participant inclusion criteria: 1. Have given written informed consent to participate 2. Be aged 50 years and over 3. Have had a recent (less than one month) symptomatic carotid atherosclerotic stroke or transient ischaemic attack (TIA) with carotid stenosis of 30-99%. This will be determined from clinical imaging such as US Duplex/ultrasound, CT Angiogram or MR Angiogram. The percentage of stenosis will be measured using NASCET criteria* *Patients with tight carotid stenosis (> 70%) will usually be offered carotid endarterectomy and therefore would not be suitable for the study. However many patients present with moderate carotid stenosis (30–70%) and do not receive carotid endarterectomy. Therefore we would anticipate that the majority of our patients will have this degree of stenosis (30-70%). In a recent observational study of PET in acute symptomati
1. Unable/unwilling to consent 2. Contraindications to taking part in MRI study as assessed by the local MRI safety questionnaire, e.g., pacemaker 3. Women of childbearing potential* 4. Contraindications to sodium valproate including hepatic dysfunction 5. Atrial fibrillation 6. Known chronic kidney disease that would preclude contrast use: i.e Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 7. Planned endarterectomy 8. Taking medication contra-indicated to sodium valproate 9. Known hypersensitivity to sodium valproate or its excipients 10 Another diagnosed chronic neurological condition (e.g. Alzheimer's, Parkinson's disease, motor neurone disease, multiple sclerosis). 11. Limited life expectancy due to another illness or chronic condition making the 2 year treatment difficult (e.g. widespread malignancy). *A woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile. Women in childbearing potential who underwent permanent sterilisation which include hysterectomy, bilateral salpingectomy and bilateral oophorectomy will be eligible.