Neurodegenerative DiseasesNCT01450891
Health Technology Assessment of Diagnostic Approaches in Alzheimer's Disease
An observational study of Neurodegenerative Diseases and Memory Disturbances, run by Maastricht University Medical Center at 4 sites in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurodegenerative Diseases, Memory Disturbances
- How many people
- 304 participants
- Where
- 4 sitesNetherlands
- Study dates
- Sep 2009to Jul 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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).
Who cannot join
- 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
Show all 9Show fewer
- Brain-tumor, epilepsy, encephalitis
- Absence of a reliable informant
- Probably not available for follow-up
Trial locations and contacts
4 sites in 1 country.
Netherlands4 sites
VU University Medical Center
Amsterdam, 1100 DD
Leiden University Medical Center
Leiden, 2333 ZA
Maastricht University Medical Center
Maastricht, 6200 MD
Radboud University Nijmegen Medical Centre
Nijmegen, 6500 HC
About this study
Official title: Novel Diagnostic Approaches for the Diagnosis of Alzheimer's Disease: Technology Assessment and Clinical Effectiveness
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.
Read more
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.
- Conditions
- Neurodegenerative Diseases, Memory Disturbances
- Keywords
- Alzheimer's disease, Diagnosis, Costs, Benefits, subjective and/or objective memory complaints
- Medical subject headings
- Neurodegenerative Diseases, Alzheimer Disease, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline
Change in cognition at 2 years
Measured by the Mini-mental state examination (MMSE).
Measured: baseline, 1 year follow up, 2 year follow up
Change in dementia severity at 2 years
Measured by the clinical dementia rating (CDR) scale.
Measured: baseline, 1 year follow up, 2 year follow up
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.
Measured: baseline, 3 months follow up, 1 year follow up, 2 year follow up
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.
Measured: baseline, 3 months follow up, 1 year follow up, 2 year follow up
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.
Measured: baseline, 3 months follow up, 1 year follow up, 2 year follow up
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 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.
Measured: baseline
Secondary outcomes (8)
Demographic changes at 2 years
Course of cognitive symptoms, Civil status, and Living situation are assessed.
Measured: baseline, 1 year follow up, 2 year follow up
General clinical changes at 2 years
Smoking behaviour, alcohol intake, length, weight, blood pressure, neuropsychological problems, and co-morbidities are assessed.
Measured: baseline, 1 year follow up, 2 year follow up
Change in behavioural and psychological problems at 2 years
Measured by the Neuropsychiatric Inventory (NPI).
Measured: baseline, 1 year follow up, 2 year follow up
Change in basic and instrumental activities in daily activities at 2 years
Measured by the Disability assessment for Dementia (DAD).
Measured: baseline, 1 year follow up, 2 year follow up
Change in depression at 2 years
Measured by the geriatric depression scale 15 (GDS-15).
Measured: baseline, 1 year follow up, 2 year follow up
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.
Measured: baseline, 1 year follow up, 2 year follow up
Change in sense of competence at 2 years
Measured by the Sense of Competence Questionnaire (SoCQ).
Measured: baseline, 1 year follow up, 2 year follow up
Change in Care-related quality of life
Assessed by the CarerQol by the informal caregiver.
Measured: baseline, 3 months follow up, 1 year follow up, 2 year follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2011 (estimated)
- Study startSep 2009
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neurodegenerative DiseasesStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 304 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Translational Molecular Medicine, Leiden University Medical Center, Radboud University Medical Center, Amsterdam UMC, location VUmc
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01450891
- Sponsor's protocol ID
- 09-3-038
- Other IDs
- 02N-101
- Status last verified
- May 2015
- First submitted
- 20 Sep 2011
- Last updated
- 28 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22883691
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Diagnostic Approaches for the Diagnosis of Alzheimer's Disease: Technology Assessment and Clinical Effectiveness
- ClinicalTrials.gov ID
- NCT01450891
- Acronym / sponsor ID
- 09-3-038
- Conditions
- Neurodegenerative Diseases, Memory Disturbances
- Keywords
- Alzheimer's disease, Diagnosis, Costs, Benefits, subjective and/or objective memory complaints
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 304 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Center for Translational Molecular Medicine, Leiden University Medical Center, Radboud University Medical Center, Amsterdam UMC, location VUmc
- Study start
- Sep 2009
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 12 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Diagnostic accuracy of Magnetic Resonance Imaging (MRI)
Time frame: baseline
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
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
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
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
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
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
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.
8 secondary outcomes
Demographic changes at 2 years
Time frame: baseline, 1 year follow up, 2 year follow up
General clinical changes at 2 years
Time frame: baseline, 1 year follow up, 2 year follow up
Change in behavioural and psychological problems at 2 years
Time frame: baseline, 1 year follow up, 2 year follow up
Change in basic and instrumental activities in daily activities at 2 years
Time frame: baseline, 1 year follow up, 2 year follow up
Change in depression at 2 years
Time frame: baseline, 1 year follow up, 2 year follow up
Change in cognitive functioning at 2 years
Time frame: baseline, 1 year follow up, 2 year follow up
Change in sense of competence at 2 years
Time frame: baseline, 1 year follow up, 2 year follow up
Change in Care-related quality of life
Time frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2015.
- Background: PubMed 22883691Handels 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.
- organizational framework for the studyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neurodegenerative Diseases and Memory Disturbances, run by Maastricht University Medical Center at 4 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic accuracy of Magnetic Resonance Imaging (MRI) (time frame: baseline). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01450891, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2015.