Clinical trial NCT01772095: ADVANCE Study: Alzheimer Disease eVAluation iN Clinical PracticE
Official title: A 6 Months, Prospective, Open-label, Observational, Non-interventional Clinical Trial to Examine the Efficacy and Safety of Donepezil (Dementis®) Administration in Patients With Dementia.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alzheimer Disease
Dementia
Cognitive Disorders
Keywords: Donepezil (Dementis)
Elderly
Lead sponsor: Elpen Pharmaceutical Co. Inc.
Sponsor class: INDUSTRY
First posted: 2013-01-21
Enrollment: 389
Sex: ALL
Minimum age (years): 50
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with dementia

Brief summary: In 1906, Dr. Alois Alzheimer first described the disease that later took his name. Today, 100 years later, 24 million people worldwide suffer from Alzheimer's disease or other dementias.

The term 'dementia' is clinical and is used to describe brain disorders that cause decline in mental functions, memory first and then speech, judging and overall behavior. Alzheimer's disease is by far the most common form of dementia, followed by vascular dementia, dementia with Lewy, the frontotemporal dementias etc.

In Greece there are 141,000 patients with dementia. With increasing life expectancy, the figures are expected to increase dramatically in the future.

Alzheimer's disease is the most common form of dementia, as well as 50-60% of patients with dementia suffer from this disease. The second most common type of dementia is vascular, ie that associated with cerebrovascular disease and is the 15-30% of all dementia cases and is most common between the ages of 60-70 years and is more common in men than women. It is estimated that 5% to 8% of people over 65 suffer from dementia, while in industrialized countries ranges at the following levels :15-25% over 85 and 32% over 90 years.

Dementia is characterized by a slow onset and progressive course. The syndrome includes disorders in general intelligence, learning and memory, problem solving, perception, judgment, executive function, language and synergy of movement, but without impairment of consciousness.

Alzheimer's disease is a neurodegenerative disorder with distinct clinical and histopathological features, although with variations from person to person.

In its early stages it is sometimes difficult to diagnose cognitive impairment from normal aging of the brain. With the passage of time, the continuous decline in recent memory, fluency, ability for spatial orientation ultimately restricts the autonomy regarding basic activities of daily life such as managing finances. The anxiety and depression complicate diagnosis in early stages, but gradually decline with loss of sensitivity. Intermediate stages of the disease require increasingly supervision in daily self-care activities, such as personal hygiene and clothing. In the advanced stages are usually essential nursing care in institutional context.

The severity of symptoms of the disease varies and is determined by premorbid factors such as education, gender, cultural background. Epidemiological studies have shown as protective factors against the onset of dementia, higher education, taking estrogen and anti-inflammatory drugs. On the other hand, age, family history of dementia, head injury, hypertension and Down syndrome are risk factors for developing the disease. Finally, some genetic factors appear to be protective, and other pressures to the disease.

Detailed description: Current treatments aim to control the symptoms of the disease. Important parameter is the early diagnosis and early care. The delay in onset of symptoms five years would reduce the incidence of disease by 50% per generation, while complementary therapies and delay entry into institutions would reduce costs considerably. This is the rationale of medication, currently until it causative treatment. The cost of dementia to society as intolerable by the year 2030 it is estimated that a 20% of the population will be over 65. Thus e.g. cost of $ 15 billion currently available in the U.S. for the care of people with dementia are likely to rise further.

Challenge of tackling Alzheimer disease is slowing the degenerative disease process, influencing with any pharmaceutical interventions in various parameters involved in the degeneration of the neuron, resulting in no further for a short-time-charge of the patient's cognition and - the possible load-relief of the family.

Cholinesterase inhibitors are now a documented, effective treatment of the symptoms of Alzheimer disease and therefore are appropriate pharmaceutical intervention. Donepezil has been shown to help and behavioral problems of dementia.

Aging and Dementia Aging as a biological phenomenon leads to irreversible morphologic changes in all body systems. The changes are related to the nervous system can eventually lead to dementia. The population of elderly people is increasing in all developed countries, thereby creating a variety of social, economic and mainly medical problems. This finding has brought interest has to those pathological conditions which are manifested by symptoms that have some qualitative similarity to those of old age and thus both contribute to further expansion in the number of this group of the population and also create diagnostic problems. Morphological, neurochemical and neuropsychological changes that occur in normal aging and dementia observed, especially in Alzheimer.

Dementias are costly illnesses. In Europe today, the cost of care for people with dementia exceeds the cost of illnesses such as heart disease, cancer and strokes.

The last 20 years have been tremendous advances in the prevention, diagnosis and treatment of dementia.

Have significantly increased our knowledge of the predisposing factors of the disease, which helps to prevent. The control of vascular risk factors (hypertension, obesity, diabetes mellitus, hypercholesterolemia, smoking) is beneficial for both the brain and the cardiovascular system. Diet low in fat, fish and vegetarian consumption associated with decreased risk of Disease Alzheimer.

The diagnosis at early clinical stages is possible. An experienced physician can diagnose Alzheimer's with certainty up to 90% by combining the diagnostic tools at his disposal (neuroimaging methods, biomarkers, genetic testing). The pathological process in the brain of patients with Alzheimer's disease begins decades before the appearance of clinical symptoms. The etiology is probably multifactorial. Today intensively sought ways identification of candidate patients and investigated the possibility of non-specific factors (such as hormones, antioxidant vitamins, or anti-inflammatory agents) can reverse or delay the pathogenic process.

Intercultural, people less educated the incidence of dementia is greater. Specially-designed studies have shown that continuing education in adulthood increases cognitive reserve and probably protects against dementia. Those who exercised spiritually (studying, reading) suffer Alzheimer's disease less frequently or in a milder form. Physical exercise and fitness also contribute significantly to the prevention of dementia.

Today's symptomatic treatment of Alzheimer disease . Our experience with drugs called angiotensin cholinesterases (ARICEPT, EXELON, REMINYL) as with the NMDA antagonist (EBIXA) demonstrated that early initiation of treatment significantly slows disease progression Alzheimer, and other dementia syndromes (Vascular and mixed dementia, dementia with Lewy bodies and Alzheimer's Dementia Parkinson).

There is also the non-drug approach the patient exercises involving memory and attention, cognitive empowerment programs, therapy memories orientation to reality. Knowledge empowerment programs aimed at the exploitation of the cognitive functions of patients who remain at a satisfactory level. By using a wide variety of stimuli and specialized methods appropriately stimulated brain of patients and achieve the desired result.

The dementia in the early stages is not easy to diagnose because the public confuses the symptoms to those of normal aging. Still prevalent misconception that nothing can help these patients.

Recent studies have shown that demented patients are usually examined by a specialist 3 years after experiencing the first symptoms of the disease. This delay in diagnosis and treatment has a negative impact on the progress of the disease. Accurate and early diagnosis of dementia, ensure early intervention, smoother transition stages of the disease and a better quality of life for patients and their families for a longer period of time. It also allows further targeted prevention and treatment strategies, medical or otherwise.

Eligibility criteria: Inclusion Criteria:

* Age 50 and older
* Diagnosis of dementia
* Rating 15\<MMSE\<24
* The patient has reliable caregivers
* Signed consent form to participate in the study after informed by reliable caregivers of the patient or another witness
* The patient is on treatment with donepezil for at least one month prior to joining the clinical trial

Exclusion Criteria:

* Severe gastrointestinal, kidney, hepatic, endocrine, pulmonary, or hematologic disease.
* Other primary psychiatric or neurological disorder.
* Clinically significant laboratory and ECG abnormalities.
* Participation in another clinical study than this
* Refusal to sign the consent form to participate in the study after informed by reliable caregivers of the patient or another witness
* The patient is on treatment with donepezil for less than a month before its integration in the clinical study

Primary outcomes:
measure: Change in Alzheimer Disease Evaluation Scales (MMSE, Clock test, IADL)from baseline until the end of the study
timeFrame: -1, 0, 3 months, 6 months
Secondary outcomes:
measure: Number of Adverse Events occured during study duration
timeFrame: 0, 3 months, 6 months
Other outcomes:
measure: Number of days which the patient has not taken his/her study medication
timeFrame: 0,3,6 months
Locations:
city: Athens
country: Greece
facility: Aiginition University Hospital
Study officials:
affiliation: Hygeia Hospital, Athens, Greece
name: Paraskevi Sakka, MD
role: STUDY_DIRECTOR
affiliation: Sismanogleio Hospital, Athens, Greece
name: Vasilios Vagenas, MD
role: STUDY_DIRECTOR
affiliation: University hospital of Alexandroupolis, Greece
name: Konstantinos Vadikollias, MD
role: STUDY_DIRECTOR
affiliation: Laiko Hospital of Athens, Greece
name: Konstantina Giannopoulou, MD
role: STUDY_DIRECTOR
affiliation: Patras, Greece
name: Ioannis Metallinos, MD
role: STUDY_DIRECTOR
affiliation: Athens, Greece
name: Antonios Mougias, MD
role: STUDY_DIRECTOR
affiliation: Athens, Greece
name: Ioannis Papatriantaphyllou, MD
role: STUDY_DIRECTOR
affiliation: Psychiatry Hospital of Thessaloniki, Greece
name: Andreas Tzimos, MD
role: STUDY_DIRECTOR
affiliation: Papageorgiou hospital of Thessaloniki, Greece
name: Xenophon Fitsoris, MD
role: STUDY_DIRECTOR
affiliation: Aiginition University Hospital of Athens
name: Antonis Politis, MD, Associate Professor
role: STUDY_CHAIR
affiliation: Attikon Hospital
name: Sokratis G Papageorgiou, MD, Associate Professor
role: STUDY_DIRECTOR
affiliation: Aiginition University Hospital of Athens
name: Evgenia Katirtzoglou, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Attikon University Hospital of Athens
name: Nikolaos Andronas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hygeia Hospital of Athens
name: Eleni Margioti, Psychologist, PhD
role: PRINCIPAL_INVESTIGATOR
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