Health Technology Assessment of Diagnostic Approaches in Alzheimer's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Maastricht University Medical Center
Sponsor:
Collaborators:
Center for Translational Molecular Medicine
Leiden University Medical Center
Radboud University
VU University Medical Center
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01450891
First received: September 20, 2011
Last updated: May 13, 2013
Last verified: May 2013
  Purpose

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 200 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.


Condition
Neurodegenerative Diseases
Memory Disturbances

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Novel Diagnostic Approaches for the Diagnosis of Alzheimer's Disease: Technology Assessment and Clinical Effectiveness

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • Diagnostic accuracy of Magnetic Resonance Imaging (MRI) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    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.

  • Change in cognition at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    Measured by the Mini-mental state examination (MMSE).

  • Change in dementia severity at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    Measured by the clinical dementia rating (CDR) scale.

  • Change in quality of life at 2 years [ Time Frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    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.

  • Health care resource use during 2 years [ Time Frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    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.

  • Change in productivity at 2 years [ Time Frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    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.

  • Diagnostic accuracy of cerebrospinal fluid (CSF) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Diagnostic test accuracy (in terms of sensitivity and specificity) of three CSF markers (CSF total tau, CSF phosphorylated tau, and CSF Aβ1-42) 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.


Secondary Outcome Measures:
  • Demographic changes at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    Course of cognitive symptoms, Civil status, and Living situation are assessed.

  • General clinical changes at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    Smoking behaviour, alcohol intake, length, weight, blood pressure, neuropsychological problems, and co-morbidities are assessed.

  • Change in behavioural and psychological problems at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    Measured by the Neuropsychiatric Inventory (NPI).

  • Change in basic and instrumental activities in daily activities at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    Measured by the Disability assessment for Dementia (DAD).

  • Change in depression at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    Measured by the geriatric depression scale 15 (GDS-15).

  • Change in cognitive functioning at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]

    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.

  • Change in sense of competence at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    Measured by the Sense of Competence Questionnaire (SoCQ).

  • Change in Care-related quality of life [ Time Frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]
    Assessed by the CarerQol by the informal caregiver.


Biospecimen Retention:   Samples Without DNA

Cerebrospinal fluid


Estimated Enrollment: 200
Study Start Date: September 2009
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
total patient group
all new consecutive patients of the participating memory clinics who are suspected of having a primary neurodegenerative disease, meaning that all patients with subjective as well as objective memory complaints are included

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

200 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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01450891

Contacts
Contact: Frans Verhey, PhD, MD 0031 43 38 84 175 f.verhey@maastrichtuniversity.nl
Contact: Pauline Aalten, PhD 0031 43 38 84 104 p.aalten@maastrichtuniversity.nl

Locations
Netherlands
VU University Medical Center Recruiting
Amsterdam, Netherlands, 1100 DD
Contact: Wiesje van der Flier, PhD         
Leiden University Medical Center Recruiting
Leiden, Netherlands, 2333 ZA
Contact: Ania Oleksik, PhD         
Maastricht University Medical Center Recruiting
Maastricht, Netherlands, 6200 MD
Contact: Frans Verhey, PhD, MD         
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Netherlands, 6500 HC
Contact: Marcel Olde-Rikkert, PhD         
Sponsors and Collaborators
Maastricht University Medical Center
Center for Translational Molecular Medicine
Leiden University Medical Center
Radboud University
VU University Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01450891     History of Changes
Other Study ID Numbers: 09-3-038, 02N-101
Study First Received: September 20, 2011
Last Updated: May 13, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Maastricht University Medical Center:
Alzheimer's disease
Diagnosis
Costs
Benefits
subjective and/or objective memory complaints

Additional relevant MeSH terms:
Neurodegenerative Diseases
Alzheimer Disease
Memory Disorders
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on August 20, 2014