Donepezil and memantine in moderate to severe Alzheimers disease - The DOMINO-AD Trial

Alzheimer s disease is a devastating and progressive degenerative disorder for which there is no cure or treatment that can halt decline into a state of total dependence upon nursing care. A number of drug treatments have been shown to make small but significant and short-term improvements in some symptoms such as memory function or agitated or withdrawn behaviour in sufferers. Even when clear improvements are not seen with treatment, many studies have shown that those patients who are given these drugs do not decline as rapidly as those who were allocated placebo over a period of 6 months. Donepezil is a cholinesterase inhibitor - a drug which has been licensed for the treatment of patients with mild to moderate Alzheimer s disease. Memantine is a member of a different class of drugs and has a license for the treatment of patients with moderate to severe Alzheimer s disease. The two drugs work in different ways in the brain and there is some evidence that patients who are treated with both drugs together will decline less rapidly than those treated with just one drug. We want to see if this is correct and to see whether the benefits of drug treatments translate into real advantages in terms of preservation of activities of daily life and quality of life in patients. Because these drugs are relatively expensive, there is debate as to whether they are really cost-effective and therefore whether or not they should be available on the NHS. The DOMINO-AD Trial will provide information about the cost-effectiveness of these treatments to inform such a decision.

This RCT will examine efficacy of drug treatments for dementia (cholinesterase inhibitors and memantine), singly and in combination, over 12 months, in 800 Alzheimer s disease (AD)patients who are already treated with a cholinesterase inhibitor but have declined to reach the transition point to moderate to severe disease. Primary outcome measures will be cognitive function, activities of daily living and cost effectiveness. Secondary outcome measures will include quality of life, institutionalisation and family carer burden. The Trial has been designed to answer questions about the treatment of patients who are representative of those seen in clinical practice in terms of outcomes that have relevance to patients, carers and society.