Health Technology Assessment of Diagnostic Approaches in Alzheimer's Disease

Neurodegenerative Diseases Clinical Trial

Official title:

Novel Diagnostic Approaches for the Diagnosis of Alzheimer's Disease: Technology Assessment and Clinical Effectiveness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01450891
• Other study ID #: 09-3-038
• Secondary ID: 02N-101
• Status: Completed
• Phase: N/A
• First received: September 20, 2011
• Last updated: May 27, 2015
• Start date: September 2009
• Est. completion date: July 2013

Study information

• Verified date: May 2015
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 304
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Alzheimer Disease
• Memory Disturbances
• Neurodegenerative Diseases

Locations

Country	Name	City	State
Netherlands	VU University Medical Center	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (5)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Center for Translational Molecular Medicine, Leiden University Medical Center, Radboud University, VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnostic accuracy of Magnetic Resonance Imaging (MRI)	Diagnostic test accuracy (in terms of sensitivity and specificity) of three MRI markers (Whole brain and hippocampal volume, white matter integrity, and functional connectivity) is determined by relating the particular marker to a reference diagnosis. 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.	baseline	No
Primary	Change in cognition at 2 years	Measured by the Mini-mental state examination (MMSE).	baseline, 1 year follow up, 2 year follow up	No
Primary	Change in dementia severity at 2 years	Measured by the clinical dementia rating (CDR) scale.	baseline, 1 year follow up, 2 year follow up	No
Primary	Change in quality of life at 2 years	Measured by the Euro-Qol-5D both by the patient and caregiver and measured by the Quality of life Alzheimer's disease state (QoL-AD) both by the patient and caregiver.	baseline, 3 months follow up, 1 year follow up, 2 year follow up	No
Primary	Health care resource use during 2 years	By means of questionnaires the health care resource usage is measured by the Resource Utilization in Dementia-questionnaire (RUD-lite) over a period of 2 years using 4 measurement moments to interpolate the data.	baseline, 3 months follow up, 1 year follow up, 2 year follow up	No
Primary	Change in productivity at 2 years	Work status, income, and productivity losses of both the patient and caregiver are assessed by the adjusted PRODISQ (PROductivity and DISease Questionnaire). The consequences of informal caregiving on paid or unpaid work are assessed by the Health and Labour Questionnaire.	baseline, 3 months follow up, 1 year follow up, 2 year follow up	No
Primary	Diagnostic accuracy of cerebrospinal fluid (CSF)	Diagnostic test accuracy (in terms of sensitivity and specificity) of three CSF markers (CSF total tau, CSF phosphorylated tau, and CSF Aß1-42) is determined by relating the particular marker to a reference diagnosis. 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.	baseline	No
Secondary	Demographic changes at 2 years	Course of cognitive symptoms, Civil status, and Living situation are assessed.	baseline, 1 year follow up, 2 year follow up	No
Secondary	General clinical changes at 2 years	Smoking behaviour, alcohol intake, length, weight, blood pressure, neuropsychological problems, and co-morbidities are assessed.	baseline, 1 year follow up, 2 year follow up	No
Secondary	Change in behavioural and psychological problems at 2 years	Measured by the Neuropsychiatric Inventory (NPI).	baseline, 1 year follow up, 2 year follow up	No
Secondary	Change in basic and instrumental activities in daily activities at 2 years	Measured by the Disability assessment for Dementia (DAD).	baseline, 1 year follow up, 2 year follow up	No
Secondary	Change in depression at 2 years	Measured by the geriatric depression scale 15 (GDS-15).	baseline, 1 year follow up, 2 year follow up	No
Secondary	Change in cognitive functioning at 2 years	A neuropsychological examination is performed using the: Rey's Verbal Learning Test, Visual Association Test, and Digit-Span to assess memory; Letter Digit Substitution Test to assess mental processing rate; and; Stroop Color-Word Test and Trail Making Test to assess attention, concentration and interference.	baseline, 1 year follow up, 2 year follow up	No
Secondary	Change in sense of competence at 2 years	Measured by the Sense of Competence Questionnaire (SoCQ).	baseline, 1 year follow up, 2 year follow up	No
Secondary	Change in Care-related quality of life	Assessed by the CarerQol by the informal caregiver.	baseline, 3 months follow up, 1 year follow up, 2 year follow up	No

External Links

•   organizational framework for the study