Parkinson's DiseaseNCT00368199
Transcranial Duplex Scanning and Single Photon Emission Computer Tomography (SPECT) in Parkinsonian Syndromes
An observational study of Parkinson's Disease and Parkinsonian Syndrome, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
The purpose of the study is to determine the sensitivity and specificity of transcranial duplex scanning (TCD) and single photon emission computer tomography (SPECT) in patients suspected of having Idiopathic Parkinson Disease (PD) or Atypical Parkinson Syndromes (APS) with as golden standard the clinical diagnosis… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson's Disease, Parkinsonian Syndrome, Multiple System Atrophy
- How many people
- 196 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Sep 2006to 15 Sep 2012
- 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: 250 Patients with unclear parkinsonism at the outpatient clinic
Who may be able to join
- Patients with unclear parkinsonism at the outpatient clinic
Who cannot join
- Known diagnosis at presentation
- Life expectation of less than two years because of a non neurological disease
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht, PO Box 5800, 6202 AZ
About this study
Official title: Diagnostic Value Transcranial Duplex Scanning and Single Photon Emission Tomography in Patients Suspected of Having Idiopathic Parkinson Disease or Atypical Parkinson Syndromes
The purpose of the study is to determine the sensitivity and specificity of transcranial duplex scanning (TCD) and single photon emission computer tomography (SPECT) in patients suspected of having Idiopathic Parkinson Disease (PD) or Atypical Parkinson Syndromes (APS) with as golden standard the clinical diagnosis after 2-year follow-up.
Read the detailed description
PD is a progressive neurodegenerative illness that affects about 50.000 people in the Netherlands. Diagnosis is based on clinical criteria. However, purely on clinical grounds, especially in the early stage, it is not possible to differentiate PD from other parkinsonian syndromes like multiple system atrophy, Progressive Supranuclear Palsy, vascular parkinsonism, drug induced parkinsonism and essential tremor. Accurate differentiation is important because treatment and prognosis varies between the different syndromes.
At present SPECT scans are used mostly. However the SPECT is only used in the minority of the patients suspected of PD mainly because the costs and the discussion about their sensitivity and specificity to diagnose PD. We are currently finishing a meta-analysis on the diagnostic value of the SPECT in patients with parkinsonian diseases.
Recently an alternative method to visualise the alterations in the cerebral dopaminergic pathways of PD patients has been proposed: TCD of the substantia nigra in the brainstem. This technique has high inter-observer reliability. Becker discovered in 1994 that patients with PD had bilateral hyperechogenicity of the substantia nigra. Neuropathological studies confirm the increased echogenicity is because of iron deposition. However the reason of the increased level of iron is unknown.
Several publications confirm the observation that up to 90% of PD patients have increased echogenicity of the substantia nigra. In healthy subjects and in patients with essential tremor this hyperintensity of the substantia nigra is only found in 10%. However 60% of the healthy subjects with increased echogenicity also have decreased nigra-striatal function on (18)-F-dopa-PET. So TCD might possibly be an early (presymptomatic) marker for PD.
If substantia nigra scanning is combined with scanning of the nucleus lentiformis, the differentiation between PD and APS is increased. Another advantage is that with the same technique the raphe nuclei can be made visible. Several studies confirm the echogenicity of raphe nuclei is decreased in PD patients with a depression.
Our own experience suggests that the positive predictive value of this technique nears that of SPECT scans. In our pilot study with 45 patients with PD or APS who underwent SPECT and TCS we found a positive prediction value of 95%. This would predict that, if TCE is compatible with PD, a SPECT does not provide additional information; so in theory one might reduce the amount of SPECT's in almost 50% of cases.
A direct compare of the diagnostic accuracy as to PD between duplex and SPECT scans has until now not been made. Our hypothesis is that the TCD of substantia nigra duplex scanning is an accurate diagnostic tool and deserves a place in the diagnostic work-up of PD/Parkinsonism patients and diagnostically efficient enough to replace 50% of SPECT scans. In comparison with SPECT duplex scanning is less costly (respectively 80 euro and 400 euro for each SPECT) and more comfortable for the patient.
Methods:
Subjects:
250 consecutive patients with new parkinsonian complaints in the out-patient clinic of our university hospital (Maastricht) and a local hospital.
Study design:
The investigator will give a clinical diagnosis at the first visit. All subjects undergo SPECT and duplex scanning, both tests will be judged blindly for the clinical diagnosis. After two years follow-up, all patients will be seen by the investigator and again a clinical diagnosis will be made (investigator is blinded for the results of the duplex and SPECT). At the end of the follow-up the sensitivity and specificity of the first clinical judgement, duplex and SPECT can be calculated. The golden standard is the clinical diagnosis at the end of the follow-up.
- Conditions
- Parkinson's Disease, Parkinsonian Syndrome, Multiple System Atrophy, Supranuclear Palsy, Progressive, Essential Tremor, Vascular Parkinsonism
- Keywords
- single photon emission computer tomography (SPECT), transcranial sonography, transcranial duplex scanning, parkinson's disease, atypical parkinson syndromes, parkinsonism, parkinsonian, diagnostic, progressive supranuclear paralysis
- Medical subject headings
- Parkinson Disease, Parkinsonian Disorders, Multiple System Atrophy, Supranuclear Palsy, Progressive, Essential Tremor, Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
Concordance of hyperechogenic SN with clinical diagnosis of Parkinson's
Hyperechogenic substabtia nigra (SN) was assessed at initial visit and after 2 years, patients were re-examined by two movement disorder specialist neurologists for a final clinical diagnosis that served as a surrogate gold standard for our study.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2006 (estimated)
- Study start1 Sep 2006
- Primary completion18 Sep 2008
- Study completion15 Sep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- 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
- 196 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Funding: Stichting Internationaal Parkinson Fonds, The Netherlands
- Responsible party
- Principal investigator, Wim Weber, Maastricht University Medical Center
- Investigators
- Wim EJ Weber, MD PhD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00368199
- Sponsor's protocol ID
- 1-Vlaar
- Status last verified
- Feb 2018
- First submitted
- 22 Aug 2006
- Last updated
- 26 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Dataset is published with PeerJ
Publications
Bouwmans AE, Vlaar AM, Mess WH, Kessels A, Weber WE. Specificity and sensitivity of transcranial sonography of the substantia nigra in the diagnosis of Parkinson's disease: prospective cohort study in 196 patients. BMJ Open. 2013 Apr 2;3(4):e002613. doi: 10.1136/bmjopen-2013-002613. Print 2013.
PubMed 23550093Bouwmans AE, Leentjens AF, Mess WH, Weber WE. Abnormal Echogenicity of the Substantia Nigra, Raphe Nuclei, and Third-Ventricle Width as Markers of Cognitive Impairment in Parkinsonian Disorders: A Cross-Sectional Study. Parkinsons Dis. 2016;2016:4058580. doi: 10.1155/2016/4058580. Epub 2016 Jan 10.
PubMed 26881179Bouwmans AE, Weber WE, Leentjens AF, Mess WH. Transcranial sonography findings related to depression in parkinsonian disorders: cross-sectional study in 126 patients. PeerJ. 2016 May 18;4:e2037. doi: 10.7717/peerj.2037. eCollection 2016.
PubMed 27231659Vlaar AM, Bouwmans AE, van Kroonenburgh MJ, Mess WH, Tromp SC, Wuisman PG, Kessels AG, Winogrodzka A, Weber WE. Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms. BMC Neurol. 2007 Sep 4;7:28. doi: 10.1186/1471-2377-7-28.
PubMed 17784944
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnostic Value Transcranial Duplex Scanning and Single Photon Emission Tomography in Patients Suspected of Having Idiopathic Parkinson Disease or Atypical Parkinson Syndromes
- ClinicalTrials.gov ID
- NCT00368199
- Acronym / sponsor ID
- 1-Vlaar
- Conditions
- Parkinson's Disease, Parkinsonian Syndrome, Multiple System Atrophy, Supranuclear Palsy, Progressive, Essential Tremor, Vascular Parkinsonism
- Keywords
- single photon emission computer tomography (SPECT), transcranial sonography, transcranial duplex scanning, parkinson's disease, atypical parkinson syndromes, parkinsonism, parkinsonian, diagnostic
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 196 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Funding: Stichting Internationaal Parkinson Fonds, The Netherlands
- Study start
- 1 Sep 2006 (actual)
- Primary completion
- 18 Sep 2008 (actual)
- Study completion
- 15 Sep 2012 (actual)
- First posted
- 24 Aug 2006 (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.
The purpose of the study is to determine the sensitivity and specificity of transcranial duplex scanning (TCD) and single photon emission computer tomography (SPECT) in patients suspected of having Idiopathic Parkinson Disease (PD) or Atypical Parkinson Syndromes (APS) with as golden standard the clinical diagnosis after 2-year follow-up.
Detailed description
PD is a progressive neurodegenerative illness that affects about 50.000 people in the Netherlands. Diagnosis is based on clinical criteria. However, purely on clinical grounds, especially in the early stage, it is not possible to differentiate PD from other parkinsonian syndromes like multiple system atrophy, Progressive Supranuclear Palsy, vascular parkinsonism, drug induced parkinsonism and essential tremor. Accurate differentiation is important because treatment and prognosis varies between the different syndromes.
At present SPECT scans are used mostly. However the SPECT is only used in the minority of the patients suspected of PD mainly because the costs and the discussion about their sensitivity and specificity to diagnose PD. We are currently finishing a meta-analysis on the diagnostic value of the SPECT in patients with parkinsonian diseases.
Recently an alternative method to visualise the alterations in the cerebral dopaminergic pathways of PD patients has been proposed: TCD of the substantia nigra in the brainstem. This technique has high inter-observer reliability. Becker discovered in 1994 that patients with PD had bilateral hyperechogenicity of the substantia nigra. Neuropathological studies confirm the increased echogenicity is because of iron deposition. However the reason of the increased level of iron is unknown.
Several publications confirm the observation that up to 90% of PD patients have increased echogenicity of the substantia nigra. In healthy subjects and in patients with essential tremor this hyperintensity of the substantia nigra is only found in 10%. However 60% of the healthy subjects with increased echogenicity also have decreased nigra-striatal function on (18)-F-dopa-PET. So TCD might possibly be an early (presymptomatic) marker for PD.
If substantia nigra scanning is combined with scanning of the nucleus lentiformis, the differentiation between PD and APS is increased. Another advantage is that with the same technique the raphe nuclei can be made visible. Several studies confirm the echogenicity of raphe nuclei is decreased in PD patients with a depression.
Our own experience suggests that the positive predictive value of this technique nears that of SPECT scans. In our pilot study with 45 patients with PD or APS who underwent SPECT and TCS we found a positive prediction value of 95%. This would predict that, if TCE is compatible with PD, a SPECT does not provide additional information; so in theory one might reduce the amount of SPECT's in almost 50% of cases.
A direct compare of the diagnostic accuracy as to PD between duplex and SPECT scans has until now not been made. Our hypothesis is that the TCD of substantia nigra duplex scanning is an accurate diagnostic tool and deserves a place in the diagnostic work-up of PD/Parkinsonism patients and diagnostically efficient enough to replace 50% of SPECT scans. In comparison with SPECT duplex scanning is less costly (respectively 80 euro and 400 euro for each SPECT) and more comfortable for the patient.
Methods:
Subjects:
250 consecutive patients with new parkinsonian complaints in the out-patient clinic of our university hospital (Maastricht) and a local hospital.
Study design:
The investigator will give a clinical diagnosis at the first visit. All subjects undergo SPECT and duplex scanning, both tests will be judged blindly for the clinical diagnosis. After two years follow-up, all patients will be seen by the investigator and again a clinical diagnosis will be made (investigator is blinded for the results of the duplex and SPECT). At the end of the follow-up the sensitivity and specificity of the first clinical judgement, duplex and SPECT can be calculated. The golden standard is the clinical diagnosis at the end of the follow-up.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 250 Patients with unclear parkinsonism at the outpatient clinic
Key inclusion criteria (1 listed)
- Patients with unclear parkinsonism at the outpatient clinic
Key exclusion criteria (2 listed)
- Known diagnosis at presentation
- Life expectation of less than two years because of a non neurological disease
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
Concordance of hyperechogenic SN with clinical diagnosis of Parkinson's
Time frame: 24 months
Hyperechogenic substabtia nigra (SN) was assessed at initial visit and after 2 years, patients were re-examined by two movement disorder specialist neurologists for a final clinical diagnosis that served as a surrogate gold standard for our study.
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 26 Feb 2018.
- Results publication: PubMed 23550093Bouwmans AE, Vlaar AM, Mess WH, Kessels A, Weber WE. Specificity and sensitivity of transcranial sonography of the substantia nigra in the diagnosis of Parkinson's disease: prospective cohort study in 196 patients. BMJ Open. 2013 Apr 2;3(4):e002613. doi: 10.1136/bmjopen-2013-002613. Print 2013.
- Results publication: PubMed 26881179Bouwmans AE, Leentjens AF, Mess WH, Weber WE. Abnormal Echogenicity of the Substantia Nigra, Raphe Nuclei, and Third-Ventricle Width as Markers of Cognitive Impairment in Parkinsonian Disorders: A Cross-Sectional Study. Parkinsons Dis. 2016;2016:4058580. doi: 10.1155/2016/4058580. Epub 2016 Jan 10.
- Results publication: PubMed 27231659Bouwmans AE, Weber WE, Leentjens AF, Mess WH. Transcranial sonography findings related to depression in parkinsonian disorders: cross-sectional study in 126 patients. PeerJ. 2016 May 18;4:e2037. doi: 10.7717/peerj.2037. eCollection 2016.
- Derived from this study: PubMed 17784944Vlaar AM, Bouwmans AE, van Kroonenburgh MJ, Mess WH, Tromp SC, Wuisman PG, Kessels AG, Winogrodzka A, Weber WE. Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms. BMC Neurol. 2007 Sep 4;7:28. doi: 10.1186/1471-2377-7-28.
- SponsorshipLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Dataset is published with PeerJ
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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.
Wim EJ Weber, MD PhD principal investigator
Maastricht University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson's Disease and Parkinsonian Syndrome, run by Maastricht University Medical Center at 1 site 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 1 inclusion and 2 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 26 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Concordance of hyperechogenic SN with clinical diagnosis of Parkinson's (time frame: 24 months). 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 NCT00368199, which also lists 4 linked publications.
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 26 Feb 2018.