Clinical trial NCT01450891: Health Technology Assessment of Diagnostic Approaches in Alzheimer's Disease
Official title: Novel Diagnostic Approaches for the Diagnosis of Alzheimer's Disease: Technology Assessment and Clinical Effectiveness
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neurodegenerative Diseases
Memory Disturbances
Keywords: Alzheimer's disease
Diagnosis
Costs
Benefits
subjective and/or objective memory complaints
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Center for Translational Molecular Medicine
name: Leiden University Medical Center
name: Radboud University Medical Center
name: Amsterdam UMC, location VUmc
First posted: 2011-10-12
Enrollment: 304
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 304 consecutive patients, of four academic memory clinics specialized in the diagnosis and treatment of memory disorders, who were suspected of having a primary neurodegenerative disease were approached for participating in the study. This included all patients with subjective and/or objective memory complaints. Eligibility criteria were chosen to represent current clinical situation and enable generalisability to clinical practice.

Brief summary: Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy (of current clinical diagnostic work-up and emerging biomarkers in Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and Cerebrospinal Fluid (CSF), 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model.

Methods/design: In a cohort design 304 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life data, costs and emerging biomarkers are gathered.

Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to the reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period.

A decision analytic model is build combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers.

Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems.


Eligibility criteria: Inclusion Criteria:

* All new consecutive patients of the participating memory clinics who are suspected of having a primary neurodegenerative disease. This means all patients with subjective and/or objective memory complaints.
* CDR 0, 0.5 or 1
* MMSE score must be 20 or higher.
* Availability of a reliable informer or proxy (who visits or contacts the patient at least once a week).

Exclusion Criteria:

* Normal Pressure Hydrocephalus (NPH)
* Huntington's disease
* Recent Transient Ischaemic Attack (TIA) (\<2 years) or Cerebral Vascular Accident (CVA) or TIA/CVA followed by cognitive impairment (within 3 months)
* History of Schizophrenia, other psychotic disorders (\< 12 months)
* Major depression (\< 12 months)
* Alcohol abuse
* Brain-tumor, epilepsy, encephalitis
* Absence of a reliable informant
* Probably not available for follow-up

Primary outcomes:
measure: Diagnostic accuracy of Magnetic Resonance Imaging (MRI)
timeFrame: baseline
measure: Change in cognition at 2 years
timeFrame: baseline, 1 year follow up, 2 year follow up
measure: Change in dementia severity at 2 years
timeFrame: baseline, 1 year follow up, 2 year follow up
measure: Change in quality of life at 2 years
timeFrame: baseline, 3 months follow up, 1 year follow up, 2 year follow up
measure: Health care resource use during 2 years
timeFrame: baseline, 3 months follow up, 1 year follow up, 2 year follow up
measure: Change in productivity at 2 years
timeFrame: baseline, 3 months follow up, 1 year follow up, 2 year follow up
measure: Diagnostic accuracy of cerebrospinal fluid (CSF)
timeFrame: baseline
Secondary outcomes:
measure: Demographic changes at 2 years
timeFrame: baseline, 1 year follow up, 2 year follow up
measure: General clinical changes at 2 years
timeFrame: baseline, 1 year follow up, 2 year follow up
measure: Change in behavioural and psychological problems at 2 years
timeFrame: baseline, 1 year follow up, 2 year follow up
measure: Change in basic and instrumental activities in daily activities at 2 years
timeFrame: baseline, 1 year follow up, 2 year follow up
measure: Change in depression at 2 years
timeFrame: baseline, 1 year follow up, 2 year follow up
measure: Change in cognitive functioning at 2 years
timeFrame: baseline, 1 year follow up, 2 year follow up
measure: Change in sense of competence at 2 years
timeFrame: baseline, 1 year follow up, 2 year follow up
measure: Change in Care-related quality of life
timeFrame: baseline, 3 months follow up, 1 year follow up, 2 year follow up
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
Study officials:
References:
citation: Handels RL, Aalten P, Wolfs CA, OldeRikkert M, Scheltens P, Visser PJ, Joore MA, Severens JL, Verhey FR. Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study. BMC Neurol. 2012 Aug 10;12:72. doi: 10.1186/1471-2377-12-72.