ROSKAMP NILVADIPINE CLINICAL TRIAL
Questions and Answers

Partnership between Roskamp and Trinity College and DARN

1. What is the Roskamp Institute?
The Roskamp Institute is a not-for-profit private research institute devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of, and potential therapies for these disorders with an emphasis on Alzheimers disease. The Institute is located in Sarasota, Florida and operates a memory clinic and clinical research offices in Tampa, Florida. A main goal of the Roskamp Institute is to discover novel and effective treatments for Alzheimer's disease.

2. What research does Trinity College Institute of Neuroscience undertake?
TCIN’s scientific mission is to improve our understanding of how the brain works in health and disease. This involves collaborations between basic and clinical investigators, working together. TCIN investigators are exploring diverse brain disorders such as schizophrenia, depression ADHD, and there is a large ageing and dementia focus particularly studying Alzheimer’s disease in both laboratory and hospital settings. Investigators in TCIN and Mercer’s Institute for research on Ageing, SJH have been working on developing clinical, biological and neuroimaging tests that will allow detection of Alzheimer’s disease at an earlier stage and are currently examining why and how people transition from mild memory problems to Alzheimer’s disease. The focus of the research is to develop novel treatments that might slow the progression or the transition to full blown Alzheimer’s disease. We need tests that detect those at risk or before they lose abilities and then institute treatments that can stop or slow progression. This is why the Roskamp study sits very nicely with ongoing work at TCIN &SJH.

3. What is the nature of the relationship between the Roskamp Institute and Trinity College Institute of Neuroscience?

4. The Roskamp Institute and Trinity College Institute of Neuroscience have formed a new collaboration harnessing the resources and knowledge of both institutes to best facilitate research into the treatment of Alzheimers Disease.
The new partnership will enable major new scientific studies to be carried out in Ireland, commencing with this novel clinical study to determine if the drug Nilvadipine might be useful in the treatment for Alzheimer’s Disease.

5. What does this new partnership aim to achieve?
The core aim of this new partnership is to further cutting edge research, the first project being this clinical trial into finding a treatment for Alzheimers Disease.

6. How was the Dublin Aging Network Group formed, and why?
Facilitate clinical research and recruitment of subjects for studies in ageing and to support academic collaboration between ageing researchers in the eastern region

7. Why are you concentrating on Dublin only?
Outpatient studies, too difficult for patients to travel long distances and be tested in one day; want to be able to see people in own home to make it easier for them to participate if they wish

NILVADIPINE Clinical Trial

8. What do you hope to learn from the Nilvadipine clinical study?
a) In mice Nilvadipine increases cerebral blood flow – we want to see whether it can do the same for Alzheimer patients.

b) In pre-clinical studies Nilvadipine increases the blood levels of amyloid in mice and reduces them in the brain – we want to see whether it can increase the levels of amyloid in the blood Alzheimer patients. This may indicate that it is clearling amyloid from the brain.

c) We want to see whether there is any change in cognitive abilities over the period of treatment that might be associated with increased cerebral blood flow.

9. What is Nilvadipine? What are its components?
Nilvapdipine is a calcium channel blocker currently used to treat hypertension (high blood pressure) and is available in Ireland on prescription. It has been used for many years and is associated with a good safety profile (few side effects).

10. Who manufacturers Nilvadipine?
Nilvadipine is manufactured by pharmaceutical company Astellas Pharma US.

11. Are there any serious side-effects of Nilvadipine?
Nilvadipine has been used for the treatment of high blood pressure for over 10 years and has a very good safety profile. The main side effect, which is of concern to us in this trial, is that it may lower subjects’ blood pressure, and we have established a protocol to monitor for this closely. Nilvadipine can also cause headache, flushing, palpitations and swelling of the legs infrequently.

12. How will the study operate? How much time is involved for patients?
There will be six weeks of treatment. Patients will be closely followed at home (four visits) and at hospital (two visits) during the study. Patients will be seen in the hospital for cerebral blood flow studies, blood pressure and cognitive evaluation. At home they will be monitored for blood pressure and cognitive status (memory etc).

The total number of hours per patient will be about 16 for the entire study.

13. Will patients be paid to undertake the study?
No, but any expenses incurred such as travel expenses, i.e. petrol, taxis will be reimbursed.

14. Who has given approval for the initial study to take place?
The study has approval from the Irish Medicines Board and the St James’s Hospital Research Ethics Committee

15. What Doctors, physicians and nurses are involved in the clinical study?
Everyone here today in part of the clinical study, plus colleagues Julia Parrish and Dr Sean Kennelly, Clinical Fellow. There are also two Research nurses Sharon Bolger and Claire Mooney.

16. What hospitals are involved?
Recruitment will be through OAP and geriatricians from the Dublin hospitals and GPs in the Dublin area. Hospitals include St James’ Hospital, Beaumont Hospital, James Connolly Memorial Hospital (Blanchardstown), Loughlinstown, Mater Hospital, St Vincent’s Hospital and the Adelaide & Meath Hospital (Tallaght)

17. Who is funding the study?
The research and study will be fully funded by the Roskamp Institute.

18. Where will the study be conducted?
The initial trial will take place in patients’ homes and also in St James Hospital Dublin.

19. How long has research into Nilvadipine as a potential treatment for Alzheimers Disease been going on?
This potential role of calcium channel blockers for use in Alzheimer’s disease began in 1996 and Nilvadipine has been actively investigated since then.

20. Why was it decided to undertake the study in Ireland? Why not in the US?
As the drug has never been sold in the US it was expeditious to conduct the trial in a European country where it was approved. Ireland was the preferred country as the well established clinical expertise and patient population lend themselves to good clinical studies.

21. How can you be sure that the clinical study won’t go terribly wrong as happened recently with the Parexel trial in London?
TGN1412 was a phase 1 clinical trial of a novel therapy never before introduced into human volunteers. By contrast Nilvadipine has been used since 1991 and millions of prescriptions have been written for this drug. Approved in Japan and countries in Europe the side effect profile is known and is generally very good. Although unexpected side effects can always occur this is mitigated by the use of drugs that have previously been widely used and studied.

22. How will patients be selected? How many patients involved?

23. How will patients consent be obtained?
Patients or their next of kin will give written consent

24. Who should carers contact about the study?
If carers or patients hear about the trial, they can contact their physician or GP who should be able to give them more information and tell them if they might be suitable for the study

25. What is the next step following the initial 8 week study?
If there are significant changes in cognition cerebral blood flow or amyloid levels we will consider a longer term study examining the ability of the drug to slow the rate of decline of Alzheimer’s. This study would be much longer – probably 18 months to 2 years.

26. How long will the initial study go on for?
Currently the study is planned to run for 18 months to 2 years but this depends on the rate of recruitment of the patients.

27. If the study and subsequent trials are successful how long would it be before a treatment reached the market?
Marketing Nilvadipine as an anti-Alzheimer drug could be a relatively quick step – perhaps taking one to two years to achieve.

Dementia/Alzheimers Disease

25. How does Dementia/Alzheimer's affect the brain?
The accumulation of a small protein called amyloid occurs in all cases of Alzheimer’s and is generally thought to be the cause of the disease. As it accumulates it causes inflammation and toxicity in and around neurons resulting in their death. With the loss of neurons memory and eventually all other cognitive functions are reduced. Amyloid also attacks blood vessels in the brain and cerebral blood flow decreases as the disease progresses.

26. How many people suffer from Alzheimers in Ireland?
Today, more than 35,000 people in Ireland have dementia, of which Alzheimer’s Disease is the most common form. The risk of developing Alzheimer’s Disease increases with age with its prevalence rising from approximately 1% in people under 65 years old to more than 25% for those over 80 years. Although rare and more commonly associated with older age, Alzheimer’s Disease can also occur in people in their 40’s and 50’s.

27. Why is it expected that the number of people suffering from dementia worldwide will increase steadily over the next 25 years?
With better healthcare people are living longer and the greatest risk factor for Azheimer’s is aging.

28. Is there any other similar research into Alzheimers Disease currently underway world wide?
Another drug of a similar class is in phase II clinical trials. This is MEM 1003 form Memory Pharma. It’s not clear whether the two drugs act the same way.

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