Subcortical ischaemic vascular dementia Mental and Behavioural Disorders Subcortical vascular dementia
Conditions
Interventions
Patients will be randomised to either amlodipine or placebo: 5 mg once daily for 2 weeks followed by 10 mg once daily for 50 weeks
Sponsors
Belfast Health and Social Care Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 09/11/2015: 1. Dementia syndrome according to the criteria a, b & d from code 290.4 of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). 2. Evidence of one or more clinical features in support of SIVD such as executive dysfunction, mood or gait disturbance or focal neurological signs 3. Multiple lacunae (>2) or diffuse lesions reaching a mean score of 2-3 across brain regions identified on baseline MRI scan. 4. sMMSE score between 15 and 26 (inclusive). 5. Age = 50 6. If patients taking a cholinesterase inhibitor or memantine, dose stable for at least three months. 7. If patients taking antidepressants, dose stable for at least four weeks. 8. CT or MRI scan consistent with the probable diagnosis of SIVD providing there has been no significant clinical change since the scan. 9. Patient has resident family or professional carer or is visited at least twice a week by carer. 10. Fluency in English is essential as the study requires questionnaires to be completed. 11. Likely to be able to participate in all scheduled evaluations and complete all required tests. 12. Provision of appropriate consent. 13. Presence of an informant, aged 18 years or over who is willing to participate in the study. Previous inclusion criteria: 1. Dementia syndrome according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) 2. Evidence of one or more clinical features in support of SIVD such as executive dysfunction, mood or gait disturbance or focal neurological signs 3. Multiple lacunae (>2) or diffuse lesions reaching a mean score of 2-3 across brain regions identified on baseline MRI scan 4. sMMSE score between 20 and 26 (inclusive) 5. Age 50 years or older 6. If patients taking a cholinesterase inhibitor or memantine, dose stable for at least three months 7. If patients taking antidepressants, dose stable for at least four weeks 8. Diagnosis of probable SIVD with supportive imaging (CT or MRI) within last 24 months 9. Patient has resident family or professional carer or is visited at least twice a week by carer 10. Fluency in English and evidence of adequate premorbid intellectual functioning 11. Likely to be able to participate in all scheduled evaluations and complete all required tests 12. Provision of appropriate consent 13. Presence of an informant who is willing to participate in the study
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 09/11/2015: 1. Severe, unstable or poorly controlled medical conditions apparent from physical examination or clinical history. 2. Moderate/severe heart disease or severe hepatic disease. 3. Significant renal insufficiency; estimated glomerular filtration rate (eGFR) <30ml/min. 4. Blood pressure (sitting) exceeds 160 mmHg systolic and/or 110 mmHg diastolic. 5. Systolic blood pressure (sitting) is less than 110mmHg. 6. Infarction involving the cortex on MRI scan. 7. Cerebrovascular event within the last six months. 8. Myocardial infarction within the last three months. 9. Already taking any calcium channel blocker. 10. Contraindications to a calcium channel blocker as per Summary of Product Characteristics (SPC) 11. Patient is unable to take trial medications. 12. Pregnant women or women who may possibly become pregnant (pre-menopausal). Females must be postmenopausal (no menses for = 12 months without an alternative medical cause) to participate in the study. 13. Female patients who are breastfeeding will be excluded. 14. AD is considered to be the primary diagnosis: i.e. a predominantly amnestic presentation or evidence of an amnestic (pre-dementia) phase or strong biomarker evidence to support a diagnosis of AD. Patients with severe hippocampal atrophy on MRI (Scheltens GR 3 and 4 on both sides (i.e. a total score (left plus right) of 6 or more) will be excluded. 15. Significant neurological disease that may affect cognition other than SIVD or AD as a concurrent pathology. 16. Current presence of a clinically significant major psychiatric disorder (e.g. Major Depressive Disorder) according to the criteria of the DSM-IV. 17. Current clinically significant systemic illness that is likely to result in deterioration of the patient’s condition or affect the patient’s safety during the study. 18. Treatment with immunosuppressive medications (e.g. systemic corticosteroids) within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted) or chemotherapeutic agents for malignancy within the last three years. 19. Other clinically significant abnormality on physical, neurological, laboratory, examination that could compromise the study or be significantly detrimental to the patient (e.g. postural hypotension diagnosed within the last year which in the opinion of the PI would exclude the patient). 20. Alcohol or drug dependence or abuse within the last two years. 21. Treated with any other investigational medication or device within 60 days. 22. Patient taking simvastatin 40 mg or greater. A patient may be switched to an alternative statin and on stable dose for three months to meet inclusion criteria. A reduction in simvastatin dose solely for the purposes of eligibility is not permitted. Previous exclusion criteria: 1. Severe, unstable or poorly controlled medical conditions apparent from physical examination or clinical history. 2. Moderate/severe heart disease or severe hepatic disease. 3. Significant renal insufficiency; estimated glomerular filtration rate (eGFR) <30ml/min. 4. Blood pressure exceeds 160 mmHg systolic and/or 110 mmHg diastolic. 5. Systolic blood pressure is less than 110mmHg. 6. Infarction involving the cortex on MRI scans. 7. Cerebrovascular event within the last six months. 8. Myocardial infarction within the last three months. 9. Already taking any calcium channel blocker. 10. Contraindications to a calcium channel blocker as per
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 09/11/2015: A change from baseline to 12 months in Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog) score. The VADAS-cog is a more detailed cognitive assessment designed to be more sensitive to the cognitive outcomes in people with vascular dementia. This assessment should be completed face to face by an assessor who will be blinded to the intervention. Previous primary outcome measures: An improvement of 2.5 points in mean Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog) from baseline to 12 months. The VADAS-cog is a more detailed cognitive assessment designed to be more sensitive to the cognitive outcomes in people with vascular dementia. This assessment should be completed face to face by an assessor who will be blinded to the intervention. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 09/11/2015: 1. Change in cognitive function measured with the Standardised Mini-Mental State Examination (sMMSE) from baseline to 12 months. 2. Change in the Trail Making test B from baseline to 12 months. The Trail Making test B is a timed measure of executive function. 3. Change in cognitive function from baseline to 12 months with a follow up at 24 months measured by Modified Telephone Interview for Cognitive Status (TICS-M). 4. Change in Clinical Global Impression of Change (CGIC) from baseline to 12 months. CGIC is a simple standardised rating of overall clinical outcome, rated by a clinician blind to treatment allocation. 5. Change in blood pressure from baseline to 12 months. 6. Change in lesion accrual from baseline to 12 months. This will be based on quantitation of lacunar lesions and diffuse white matter lesions measured quantitatively by MRI. 7. Change in health-related quality of life from baseline to 12 months measured with the EuroQol Group EQ-5D Health Questionnaire (EQ-5D-5L) and the Dementia Quality of Life-Proxy (DEMQOL-Proxy), a carer-rated and disease-specific measure of quality of life in dementia. 8. Change in activities of daily living from baseline to 12 months measured using the Disability Assessment in Dementia (DAD). 9. Change in non-cognitive dementia symptoms from baseline to 12 months measured with the Neuropsychiatric Inventory Caregiver Distress (NPI-D). 10. Change in care-giver burden from baseline to 12 months measured with the 12 item General Health Questionnaire (GHQ-12), and care-giver health-related quality of life measured with the EQ-5D-5L. 11. Cost-effectiveness measured as the combination of costs generated from the Client Service Receipt Inventory (CSRI). 12. Institutionalisation defined as permanent transition from living in an independent household to a care home, nursing home, NHS continuing care unit or hospital and measured with questions taken from the CSRI. Previous se | — |
Countries
United Kingdom
Outcome results
None listed