Idiopathic Parkinson's DiseaseIPDNCT02045420
Vascular Abnormalities in Idiopathic Parkinson's Disease
An observational study of Idiopathic Parkinson's Disease, run by University of Saskatchewan at 1 site in Canada.
Trial summary
The purpose of this study is to use non-invasive Magnetic Resonance Imaging (MRI) scans to investigate venous insufficiency, brain iron levels and white matter hyperintensities (WMHs) to determine if there is direct correlation with Idiopathic Parkinson's Disease (IPD). Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Idiopathic Parkinson's Disease
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2013to Mar 2017
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: The study population will be comprised of patients with Idiopathic Parkinson's Disease and Age-Matched Normal Volunteers
Who may be able to join
- Idiopathic Parkinson's Disease
Who cannot join
- Not MRI Compatible
- Diabetes
- Hypertension or Cardiac disease
- History of a Stroke
- Cardiac Pacemaker
- Have had Surgery for an Aneurysm
Show all 9Show fewer
- Major Surgery within the last 8 weeks
- Claustrophobia
- Pregnant or Nursing
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to use non-invasive Magnetic Resonance Imaging (MRI) scans to investigate venous insufficiency, brain iron levels and white matter hyperintensities (WMHs) to determine if there is direct correlation with Idiopathic Parkinson's Disease (IPD).
Idiopathic Parkinson's disease (IPD) is the second most common neurodegenerative disease after Alzheimer's disease and it affects roughly 0.1% to 0.3% of the population. The risk of having IPD increases with age and the median onset age is about 60 years. The etiology of IPD remains unknown. Generally, Parkinson's patients show a reduction of dopamine levels in the deep grey matter of the brain over time. Many clinically diagnosed cases of IPD are associated with white matter hyperintensities (WMH) and elevated brain iron levels. Furthermore, in the last few years there has been an increasing interest in the role of veins in neurodegenerative diseases. More attention has been paid to the extracranial veins as being potential sources of venous hypertension. The obstructed veins are thought to cause venous insufficiency. By using MRI techniques, the investigators can not only obtain qualitative vascular information but also quantitative arterial and venous blood flow measurements.
Read the detailed description
Experimental plans: All patients and controls will consent to be subjects in this study. Data will be collected on the Siemens Skyra 3T scanner at the University of Saskatchewan using a 16 channel head/neck coil arrangement. The investigators main approach in this research is to collect MR data on the vasculature in the brain and neck, the iron content in the brain, and standard anatomical scans for 20 patients with idiopathic Parkinson's disease and 10 age matched normal subjects. MR venography, flow quantification and susceptibility weighted imaging will be used.
Anatomic MR venography (MRV): Contrast enhanced MRV is widely regarded as the optimal method for evaluation of disease involving the dural venous sinuses. It is an accurate, reliable and robust method for assessing sino-venous pathology such as thrombosis and tumor invasion. MRV is also able to demonstrate pathology involving larger cerebral veins. The investigators will be able to record both anatomic variants as well as any stenosis. Extracranially, the investigators will look for any significant variants or stenosis affecting the jugular venous system, the vertebral venous system and the azygous system. Data will be analyzed to separately display and evaluate the structure of arteries and veins in the head and neck. The maximum intensity projection (MIP) of the whole series will be generated in the coronal view. The major arteries will be evaluated as well as major veins of interest for the structural analysis including the transverse sinuses, the internal and external jugular veins, vertebral veins and deep cervical veins which usually serve as collaterals in case of flow abnormalities in the jugular veins. Cross sectional areas (CSA) of suspicious stenotic regions will also be measured to validate whether the variation seen in these CSA are veins stenosis or not.
Flow quantification (FQ): Pathological change in cerebrospinal venous drainage will be reflected by upstream disturbance of venous flow. Phase contrast MR flow techniques allow the investigators to interrogate venous flow. By applying FQ techniques to the dural venous sinuses, investigators hope to characterize the interplay between anatomic venous obstruction and pathologically altered drainage. By understanding this relationship, the investigators can gain deeper insight into the mechanism by which cerebrospinal venous insufficiency interacts with iron homeostasis mechanisms and ultimately with the pathogenesis of Parkinson's disease. Dural sinus hemodynamics can be studied non-invasively with phase contrast FQ. The phase contrast flow quantification (PCFQ) images will be used to analyze the through-plane cerebral spinal fluid in the neck (C2/C3 level), as well as blood flow in the neck (C2/C3 and C6/C7 levels), the superior sagittal sinus (SSS), both left and right transverse sinus, the straight sinus, both the extra cranial jugular and vertebral veins and Dural Sinus. Areas of interest will be drawn around the veins and arteries of interest and flow will be calculated over a full cardiac cycle. Thirty time points will be collected for each cardiac cycle by using a retroactive pulse trigger. The vessels of interest will include: the internal and external jugular veins (IJVs, EJVs), vertebral veins, deep cervical veins, common carotid arteries and vertebral arteries. The investigators will be evaluating the integrated flow, the average velocity, the volume flow rate, as well as negative and positive flow rate. This will be assessed in the cervical arteries to compare the inflow and outflow of the brain. Abnormalities may be identified by stressing the system, i.e., with a breath hold. Finally a large number of quantitative measures will be made on all the arteries and veins in the neck to assess both individual variants and total flow in the brain.
Measuring Iron in the basal ganglia and thalamus using Susceptibility Weighted Imaging (SWI): A presence of iron not only in lesions, but now more importantly in the basal ganglia and thalamus has been shown in IPD patients. The latter shows iron build up at the confluence of the draining veins in these areas. SWI can be run to show iron deposition in several areas of interest within the brain. SWI has very high spatial resolution and is an optimal method to study the small internal cerebral venous system. The ability to measure the amount of non-heme iron in the brain will facilitate a better understanding of the disease progression and may help in predicting the treatment outcome. Iron deposition will be evaluated from the SWI images. To measure iron content in grey matter, investigators will look at iron in the following eight regions: caudate nucleus, globus pallidus, putamen, thalamus, pulvinar thalamus (as it appears to be affected much before the rest of the thalamus), substantia nigra, red nucleus and dentate nucleus. For each deep gray matter structure, two major regions of interest will be analyzed: the entire object drawn manually and the region-of-interest that has much higher iron content. The investigators will provide the following information for these regions: iron content in the abnormal part of the structure (the investigators refer to this as the high iron content region); the area of this region; the average iron per pixel in this region; and also the investigators will quote the same three values for the total iron in these structures.
- Conditions
- Idiopathic Parkinson's Disease
- Keywords
- Idiopathic Parkinson's Disease, Magnetic Resonance Imaging, MR Venography, Flow Quantification, Susceptibility Weighted Imaging
- Medical subject headings
- Parkinson 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 |
|---|---|---|
| Normal Participants | The investigators will use "normal" age-matched volunteers to compare against the Idiopathic Parkinson's Disease Patients | |
| Idiopathic Parkinson's Disease Patients | The investigators will observe the MR scans to determine the vascular flow, brain lesions and brain iron levels in this group. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of Vascular Flow within the Internal Jugular Veins(IJVs), External Jugular Veins(EJVs) and Dural Sinus
Vascular Flow Rates within the head and neck will be measured using the MRI Flow Quantification tool. There is specific interest to correlate flow in the Dural Sinus, IJVs and EJVs and compare the measured flows with each participant's Unified Parkinson's Disease Rating Scale (UPDRS) Score.
Measured: MRI Baseline Scan: Not a Longitudinal Study
Secondary outcomes (1)
Measurement of Brian Iron using MRI Susceptibility Weighted Imaging Iron Quantification tools
Brain Iron levels within the Red Nuclei, Substantia Nigra, Globus Pallidus, Putamen, Caudate Nucleus and Thalamus will be measured. Given that Brain Iron levels increase with age, there is specific interest to correlate age dependent Brain Iron Levels to each participant's Unified Parkinson's Disease Rating Scale (UPDRS) Score.
Measured: MRI Baseline Scan: Not a Longitudinal Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2014 (estimated)
- Study startDec 2013
- Primary completionOct 2016 (estimated)
- Study completionMar 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic 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
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Saskatchewan
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Szkup, MD, Principal investigator, University of SaskatchewanPaul Babyn, MD, Study director, University of Saskatchewan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02045420
- Sponsor's protocol ID
- BIO13-204
- Acronym
- IPD
- Status last verified
- Nov 2015
- First submitted
- 11 Dec 2013
- Last updated
- 2 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vascular Abnormalities in Idiopathic Parkinson's Disease
- ClinicalTrials.gov ID
- NCT02045420
- Acronym / sponsor ID
- IPD / BIO13-204
- Conditions
- Idiopathic Parkinson's Disease
- Keywords
- Idiopathic Parkinson's Disease, Magnetic Resonance Imaging, MR Venography, Flow Quantification, Susceptibility Weighted Imaging
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of SaskatchewanUniversity, hospital or other
- Study start
- Dec 2013
- Primary completion
- Oct 2016 (estimated)
- Study completion
- Mar 2017 (estimated)
- First posted
- 24 Jan 2014 (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 this study is to use non-invasive Magnetic Resonance Imaging (MRI) scans to investigate venous insufficiency, brain iron levels and white matter hyperintensities (WMHs) to determine if there is direct correlation with Idiopathic Parkinson's Disease (IPD).
Idiopathic Parkinson's disease (IPD) is the second most common neurodegenerative disease after Alzheimer's disease and it affects roughly 0.1% to 0.3% of the population. The risk of having IPD increases with age and the median onset age is about 60 years. The etiology of IPD remains unknown. Generally, Parkinson's patients show a reduction of dopamine levels in the deep grey matter of the brain over time. Many clinically diagnosed cases of IPD are associated with white matter hyperintensities (WMH) and elevated brain iron levels. Furthermore, in the last few years there has been an increasing interest in the role of veins in neurodegenerative diseases. More attention has been paid to the extracranial veins as being potential sources of venous hypertension. The obstructed veins are thought to cause venous insufficiency. By using MRI techniques, the investigators can not only obtain qualitative vascular information but also quantitative arterial and venous blood flow measurements.
Detailed description
Experimental plans: All patients and controls will consent to be subjects in this study. Data will be collected on the Siemens Skyra 3T scanner at the University of Saskatchewan using a 16 channel head/neck coil arrangement. The investigators main approach in this research is to collect MR data on the vasculature in the brain and neck, the iron content in the brain, and standard anatomical scans for 20 patients with idiopathic Parkinson's disease and 10 age matched normal subjects. MR venography, flow quantification and susceptibility weighted imaging will be used.
Anatomic MR venography (MRV): Contrast enhanced MRV is widely regarded as the optimal method for evaluation of disease involving the dural venous sinuses. It is an accurate, reliable and robust method for assessing sino-venous pathology such as thrombosis and tumor invasion. MRV is also able to demonstrate pathology involving larger cerebral veins. The investigators will be able to record both anatomic variants as well as any stenosis. Extracranially, the investigators will look for any significant variants or stenosis affecting the jugular venous system, the vertebral venous system and the azygous system. Data will be analyzed to separately display and evaluate the structure of arteries and veins in the head and neck. The maximum intensity projection (MIP) of the whole series will be generated in the coronal view. The major arteries will be evaluated as well as major veins of interest for the structural analysis including the transverse sinuses, the internal and external jugular veins, vertebral veins and deep cervical veins which usually serve as collaterals in case of flow abnormalities in the jugular veins. Cross sectional areas (CSA) of suspicious stenotic regions will also be measured to validate whether the variation seen in these CSA are veins stenosis or not.
Flow quantification (FQ): Pathological change in cerebrospinal venous drainage will be reflected by upstream disturbance of venous flow. Phase contrast MR flow techniques allow the investigators to interrogate venous flow. By applying FQ techniques to the dural venous sinuses, investigators hope to characterize the interplay between anatomic venous obstruction and pathologically altered drainage. By understanding this relationship, the investigators can gain deeper insight into the mechanism by which cerebrospinal venous insufficiency interacts with iron homeostasis mechanisms and ultimately with the pathogenesis of Parkinson's disease. Dural sinus hemodynamics can be studied non-invasively with phase contrast FQ. The phase contrast flow quantification (PCFQ) images will be used to analyze the through-plane cerebral spinal fluid in the neck (C2/C3 level), as well as blood flow in the neck (C2/C3 and C6/C7 levels), the superior sagittal sinus (SSS), both left and right transverse sinus, the straight sinus, both the extra cranial jugular and vertebral veins and Dural Sinus. Areas of interest will be drawn around the veins and arteries of interest and flow will be calculated over a full cardiac cycle. Thirty time points will be collected for each cardiac cycle by using a retroactive pulse trigger. The vessels of interest will include: the internal and external jugular veins (IJVs, EJVs), vertebral veins, deep cervical veins, common carotid arteries and vertebral arteries. The investigators will be evaluating the integrated flow, the average velocity, the volume flow rate, as well as negative and positive flow rate. This will be assessed in the cervical arteries to compare the inflow and outflow of the brain. Abnormalities may be identified by stressing the system, i.e., with a breath hold. Finally a large number of quantitative measures will be made on all the arteries and veins in the neck to assess both individual variants and total flow in the brain.
Measuring Iron in the basal ganglia and thalamus using Susceptibility Weighted Imaging (SWI): A presence of iron not only in lesions, but now more importantly in the basal ganglia and thalamus has been shown in IPD patients. The latter shows iron build up at the confluence of the draining veins in these areas. SWI can be run to show iron deposition in several areas of interest within the brain. SWI has very high spatial resolution and is an optimal method to study the small internal cerebral venous system. The ability to measure the amount of non-heme iron in the brain will facilitate a better understanding of the disease progression and may help in predicting the treatment outcome. Iron deposition will be evaluated from the SWI images. To measure iron content in grey matter, investigators will look at iron in the following eight regions: caudate nucleus, globus pallidus, putamen, thalamus, pulvinar thalamus (as it appears to be affected much before the rest of the thalamus), substantia nigra, red nucleus and dentate nucleus. For each deep gray matter structure, two major regions of interest will be analyzed: the entire object drawn manually and the region-of-interest that has much higher iron content. The investigators will provide the following information for these regions: iron content in the abnormal part of the structure (the investigators refer to this as the high iron content region); the area of this region; the average iron per pixel in this region; and also the investigators will quote the same three values for the total iron in these structures.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal Participants | – | –The investigators will use "normal" age-matched volunteers to compare against the Idiopathic Parkinson's Disease Patients |
| Idiopathic Parkinson's Disease Patients | – | –The investigators will observe the MR scans to determine the vascular flow, brain lesions and brain iron levels in this group. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population will be comprised of patients with Idiopathic Parkinson's Disease and Age-Matched Normal Volunteers
Key inclusion criteria (1 listed)
- Idiopathic Parkinson's Disease
Key exclusion criteria (9 listed)
- Not MRI Compatible
- Diabetes
- Hypertension or Cardiac disease
- History of a Stroke
- Cardiac Pacemaker
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
Measurement of Vascular Flow within the Internal Jugular Veins(IJVs), External Jugular Veins(EJVs) and Dural Sinus
Time frame: MRI Baseline Scan: Not a Longitudinal Study
Vascular Flow Rates within the head and neck will be measured using the MRI Flow Quantification tool. There is specific interest to correlate flow in the Dural Sinus, IJVs and EJVs and compare the measured flows with each participant's Unified Parkinson's Disease Rating Scale (UPDRS) Score.
1 secondary outcome
Measurement of Brian Iron using MRI Susceptibility Weighted Imaging Iron Quantification tools
Time frame: MRI Baseline Scan: Not a Longitudinal Study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2015.
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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.
Peter Szkup, MD principal investigator
University of Saskatchewan
Paul Babyn, MD study director
University of Saskatchewan
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 Idiopathic Parkinson's Disease, run by University of Saskatchewan at 1 site in Canada.
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 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: status not confirmed, as of the sponsor's last update on 2 Dec 2015. 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 Canada. 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?
Results are not available in the source record.
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?
Measurement of Vascular Flow within the Internal Jugular Veins(IJVs), External Jugular Veins(EJVs) and Dural Sinus (time frame: MRI Baseline Scan: Not a Longitudinal Study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Dec 2015.