ONGOING STUDIES

ICTUS

The Impact of treatment with Anticholinesterase Inhibitors (AChE I) on Europeans with Alzheimer’s Disease (AD)

acronym : ICTUS (Impact of Cholinergic Treatment Use)

ICTUS is a prospective 2 years observational study which co-ordinates the centralisation of patient data available within the study’s individual centres.


OBJECTIVES

The primary objective is to determine whether treatment with AChE I changes the pattern of institutionalisation in European AD patients.

Acetylcholinesterase inhibitors (AChE I) have been shown to afford modest benefits on cognitive functioning in patients with AD. A systematic review by the Cochrane Collaboration states “the practical importance of these changes to patients and carers is unclear”


Definition of "AChE I " treatment success:

“There is a need to redefine treatment success in Alzheimer’s disease. Moreover, it is important that all healthcare professionals, especially budget holders, accept this re-definition so that realistic expectations can be set and patients can benefit from available treatments. Assessments of treatments for Alzheimer’s disease should consider more than cognition. Outcomes should be clinically relevant and measure ADL, behaviour, caregiver burden, quality of life and resource utilisation, in addition to cognition. Furthermore, ‘responders’ are those with ‘improvements’ in any of these areas and those who experience a delay in progressive decline. Relative stabilisation in an Alzheimer’s disease patient’s clinical condition is an important outcome that should be considered for use in clinical trials, in clinical practice and when making decisions about healthcare budgets. Focussing only on transient improvement in scores may deny patients and caregivers important benefits.”

Winblad B,et al Int. J. Geriat. Psychiatry 2001;16:653-666

The primary objective

is to take advantage of the differences in prescription rates across Europe in order to examine whether long-term treatment with AChE I modifies the rate of change of Clinical Dementia Rating scale (CDR; a score providing a global rating of the severity of dementia) in European AD patients. This will be done within the setting of the European Alzheimer’s Disease Consortium (EADC) which is a fully functional network of European clinical centres of excellence specialising in AD.

The secondary objectives are to determine

  • The natural history of AD in Europe (cognitive impairment, and non cognitive domains of activities of daily living, behavioral disorders, and dependency).
  • The impact of AChE I treatment on natural history and the caregiver burden of AD.
  • The impact of AChE I treatments on the financial burden of AD in Europe.
  • The predictive factors for decline using hospitalisation and institutionalisation as markers of decline in AD.
  • Identification of patient subgroups which respond differentially to AChE I treatment, using neuro-imaging to stratify patients by presence of cerebrovascular changes.

It does not require any modification in the normal prescribing practice of participating centres but takes advantage of the differences in prescribing rates across Europe. Patients with AD will be recruited into either a treated (with AChE I) or non treated patient group and reviewed 6 monthly. The primary outcome measure is a deterioration of one level on the “clinical dementia rating” scale (CDR).

Central co-ordination
of the project will be the responsibility of the Toulouse University Hospital. The central co-ordinator of the study is Prof. B Vellas, physician in general internal medicine and geriatrics

The central co-ordination
is responsible for overall project co-ordination, financial management, control of deliverables and communication with the EU. He will report to the steering committee at least twice a year during ICTUS and EADC meetings and to the EU as agreed in the contract. The central co-ordinator will chair the monthly ICTUS Project management Group meetings.

Biostatistics and Data management Unit
of the project is based at the University of Toulouse, Department of Epidemiology, Health economics and Public Health, INSERM unit 558, and shares office space with the central co-ordination. The Biostatistics and Data management co-ordinator for the study will be Dr. Sandrine Andrieu.

The partnership:

All partners are members of the EADC

City Country Principal investigator (PI)
Toulouse France Vellas B.
Manchester UK Burns A.
Lille France Pasquier F.
Brescia Italy Frisoni G.
Liège Belgium Salmon E.
Newcastle United Kingdom McKeith I.
Barcelona Spain Boada M.
Bordeaux France Dartigues J.F.
Munich Germany Kurz A.
Nijmejen Netherlands Olde-Rikkert M.G.M.
Paris France Rigaud A.S.
Aberdeen UK Whalley L.
Huddinge Sweden Winblad B.
Warwick UK Sinclair A.
Mannheim Germany Frolich L.
Amsterdam Netherlands Scheltens P.
Madrid Spain Ribera C.
Montpellier France Touchon J.
Helsinki Finland Erkinjuntti T.
Nice France Robert P.
Lausanne Switzerland Camus V.
Luxembourg Luxembourg George J. (Alzheimer Europe)
Barcelona Spain Salva A.
Copenhagen Denmark Waldmar G.
Basel Switzerland Staehelin H.B.
Swindon UK Bullock R.
Thesaloniki Greece Costa-Tsolaki M.
Genoa Italy Rodriguez G.
Bucharest Romania Spiru L.
Bath United Kingdom Jones R.W.
Goettingen Germany Stoppe G.
Perugia Italy Cherubini A.
Pamplona Spain Gomez-Isla T.
Tours France Camus V.
Cordoba Spain Lopez F.
C5R Canada Serge Gautier
ADCS USA Leon Thal


Graphical presentation of ICTUS study components