Parkinson's DiseaseNCT02605161
Imaging Blood Brain Imaging Dysfunction in Parkinson's Disease
An observational study of Parkinson's Disease and Movement Disorders, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
The purpose of this study is to evaluate the blood brain barrier in the striatum of patients that have other types of movement disorders compared to patients with Parkinson's Disease that are receiving similar treatment, to determine if a there is a disruption of the blood brain barrier in patients with Parkinson's… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Parkinson's Disease, Movement Disorders
- How many people
- 17 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2015to 8 Sep 2020
- 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
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients having movement disorders undergoing deep brain stimulation (DBS) of the internal segment of the globus pallidus for treatment of motor symptoms refractory to medical therapy at the Ottawa Hospital, Civic Campus, will be recruited to participate in this pilot study. The cohort will include 10 PD patients and 10 control subjects. The PD subjects will have received a diagnosis of PD using established clinical criteria following clinical assessment at the Movement Disorders Clinic of The Ottawa Hospital. The 10 control subjects will consist of those undergoing DBS and assessed in the same clinic with a clinical diagnosis of either essential tremor or cervical dystonia.
Who may be able to join
- Disease burden is dominated by motor symptoms such as rigidity, bradykinesia, akinesia, and tremor;
- Medications have been optimized by a movement disorder neurologist;
- Adequate social support to assist with preoperative recovery and problems during subsequent programming;
- No major mood disorder and any mood disorders are medically optimized;
- No major cognitive impairment;
- No underlying medical conditions that would preclude surgery;
- Adequate response to levodopa, as assessed by UPDRS-3 on and off levodopa. All participants has at least a 30% improvement;
- eGRF>30
Who cannot join
- Disease burden is not dominated by motor symptoms such as rigidity, bradykinesia, akinesia, and tremor;
- Medications have not bee optimized by a movement disorder neurologist;
- There is not adequate social support to assist with pre-operative recovery or problems during subsequent programming;
- Presence of major mood disorders or any mood disorders not medically optimized;
- Presence of major cognitive impairment;
- Presence of underlying medical conditions that would preclude surgery;
- Inadequate response to levodopa;
- eGFR<30
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to evaluate the blood brain barrier in the striatum of patients that have other types of movement disorders compared to patients with Parkinson's Disease that are receiving similar treatment, to determine if a there is a disruption of the blood brain barrier in patients with Parkinson's Disease.
Read the detailed description
Parkinson's disease (PD) is the most common neurodegenerative movement disorder of aging. Its cause is unknown. Current evidence supports a stress-diathesis model of pathogenesis whereby some yet-to-be identified environmental trigger conspires with a permissive genetic background to initiate the disease process. Based on neuropathological observations in other neurodegenerative diseases, such as chronic traumatic encephalopathy where pathological protein aggregates form in close association with damaged blood vessels, investigators have hypothesized that the environmental trigger resides in the bloodstream. As a corollary of this hypothesis, investigators propose that the PD pathological process begins in the brain of affected individuals only after disruption of the blood brain barrier (BBB), thereby allowing access of the inciting agent to nigrostriatal axon terminals in the neostriatum. This forms the foundation for the investigators' hypothesis that the BBB in the neostriatum of PD patients is disrupted. Indeed, in a post-mortem study, investigators demonstrated histopathological evidence for significant striatal BBB disruption in sections of striatum from PD subjects relative to age-matched controls. Critics of this study indicate that post-mortem effects may result in artefactual disruption of the BBB, calling into question the validity and relevance of this potentially important finding to PD pathogenesis and progression. Therefore, investigators are performing this imaging study of live PD patients as a follow-up of their convincing post-mortem study to definitively establish whether BBB dysfunction is a feature of PD.
The neostriatal BBB is dysfunctional in PD patients relative to controls and this can be demonstrated by significantly increased parenchymal enhancement on magnetic resonance imaging (MRI).
The results of these studies could have important implications for the understanding of PD pathogenesis. There is emerging evidence that the key pathogenetic event in PD pathogenesis, aggregation of alpha-synuclein, begins within the axon terminals of neurons. The neurons most severely affected in PD reside in the substantia nigra and project to the neostriatum. Demonstrating disruption of the BBB in the PD striatum would render nigrostriatal axon terminals susceptible to a blood-borne disease trigger and allow researchers to generate hypotheses regarding the identity of this trigger. Immune/inflammatory candidates are particularly attractive in this regard. The results this study may also have therapeutic implications. For example, if alpha-synuclein disaggregating agents achieve therapeutic utility in the coming years, our studies may indicate that such agents may be capable of accessing nigrostriatal axon terminals without requiring pharmaceutical or mechanical disruption of the BBB.
- Conditions
- Parkinson's Disease, Movement Disorders
- Keywords
- Blood brain barrier, movement disorder, deep brain stimulation, essential tremor, cervical dystonia, magnetic resonance imaging, neostriatum
- Medical subject headings
- Parkinson Disease, Movement Disorders, Essential Tremor, Torticollis
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 |
|---|---|---|
| Parkinson's disease group | * patients diagnosed with Parkinson's disease by a movement disorder specialist from the deep brain stimulation program at The Ottawa Hospital, Civic Campus * to undergo pre-operative MRI with contrast | |
| Control group | * patients diagnosed with either essential tremor or cervical dystonia by a movement disorder specialist from the deep brain stimulation program at The Ottawa Hospital, Civic Campus * to undergo pre-operative MRI with contrast |
What is being measured
The primary outcome is the main question the study is designed to answer.
Degree of contrast enhancement
Pre-contrast images will be used as mask images and will be digitally substracted from post-contrast images to obtain the "difference" images. From the "difference images", two neuroradiologists blinded to the clinical status of the patient will assess the degree enhancement in the striatum (none,mild, moderate, marked).
Measured: one year
Secondary outcomes (1)
Permeability of blood brain barrier in the striatum
Quantitative assessment of the permeability of the blood brain barrier in the striatum will be assessed using dynamic contrast enhanced MRI. Specifically, the volume transfer constant (Ktrans) will be measured from the striatum in the control and patient groups.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2015 (estimated)
- Study startNov 2015
- Primary completion8 Sep 2020
- Study completion8 Sep 2020
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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thanh B Nguyen, MD, FRCP, Principal investigator, The Ottawa Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02605161
- Sponsor's protocol ID
- 20150770-01H
- Status last verified
- Dec 2020
- First submitted
- 3 Nov 2015
- Last updated
- 31 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Warner TT, Schapira AH. Genetic and environmental factors in the cause of Parkinson's disease. Ann Neurol. 2003;53 Suppl 3:S16-23; discussion S23-5. doi: 10.1002/ana.10487.
PubMed 12666095Gray MT, Woulfe JM. Striatal blood-brain barrier permeability in Parkinson's disease. J Cereb Blood Flow Metab. 2015 May;35(5):747-50. doi: 10.1038/jcbfm.2015.32. Epub 2015 Mar 11.
PubMed 25757748Schulz-Schaeffer WJ. The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia. Acta Neuropathol. 2010 Aug;120(2):131-43. doi: 10.1007/s00401-010-0711-0. Epub 2010 Jun 20.
PubMed 20563819Orr CF, Rowe DB, Mizuno Y, Mori H, Halliday GM. A possible role for humoral immunity in the pathogenesis of Parkinson's disease. Brain. 2005 Nov;128(Pt 11):2665-74. doi: 10.1093/brain/awh625. Epub 2005 Oct 11.
PubMed 16219675
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging Blood Brain Imaging Dysfunction in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT02605161
- Acronym / sponsor ID
- 20150770-01H
- Conditions
- Parkinson's Disease, Movement Disorders
- Keywords
- Blood brain barrier, movement disorder, deep brain stimulation, essential tremor, cervical dystonia, magnetic resonance imaging, neostriatum
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- Nov 2015 (actual)
- Primary completion
- 8 Sep 2020 (actual)
- Study completion
- 8 Sep 2020 (actual)
- First posted
- 16 Nov 2015 (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 evaluate the blood brain barrier in the striatum of patients that have other types of movement disorders compared to patients with Parkinson's Disease that are receiving similar treatment, to determine if a there is a disruption of the blood brain barrier in patients with Parkinson's Disease.
Detailed description
Parkinson's disease (PD) is the most common neurodegenerative movement disorder of aging. Its cause is unknown. Current evidence supports a stress-diathesis model of pathogenesis whereby some yet-to-be identified environmental trigger conspires with a permissive genetic background to initiate the disease process. Based on neuropathological observations in other neurodegenerative diseases, such as chronic traumatic encephalopathy where pathological protein aggregates form in close association with damaged blood vessels, investigators have hypothesized that the environmental trigger resides in the bloodstream. As a corollary of this hypothesis, investigators propose that the PD pathological process begins in the brain of affected individuals only after disruption of the blood brain barrier (BBB), thereby allowing access of the inciting agent to nigrostriatal axon terminals in the neostriatum. This forms the foundation for the investigators' hypothesis that the BBB in the neostriatum of PD patients is disrupted. Indeed, in a post-mortem study, investigators demonstrated histopathological evidence for significant striatal BBB disruption in sections of striatum from PD subjects relative to age-matched controls. Critics of this study indicate that post-mortem effects may result in artefactual disruption of the BBB, calling into question the validity and relevance of this potentially important finding to PD pathogenesis and progression. Therefore, investigators are performing this imaging study of live PD patients as a follow-up of their convincing post-mortem study to definitively establish whether BBB dysfunction is a feature of PD.
The neostriatal BBB is dysfunctional in PD patients relative to controls and this can be demonstrated by significantly increased parenchymal enhancement on magnetic resonance imaging (MRI).
The results of these studies could have important implications for the understanding of PD pathogenesis. There is emerging evidence that the key pathogenetic event in PD pathogenesis, aggregation of alpha-synuclein, begins within the axon terminals of neurons. The neurons most severely affected in PD reside in the substantia nigra and project to the neostriatum. Demonstrating disruption of the BBB in the PD striatum would render nigrostriatal axon terminals susceptible to a blood-borne disease trigger and allow researchers to generate hypotheses regarding the identity of this trigger. Immune/inflammatory candidates are particularly attractive in this regard. The results this study may also have therapeutic implications. For example, if alpha-synuclein disaggregating agents achieve therapeutic utility in the coming years, our studies may indicate that such agents may be capable of accessing nigrostriatal axon terminals without requiring pharmaceutical or mechanical disruption of the BBB.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Parkinson's disease group | – | –* patients diagnosed with Parkinson's disease by a movement disorder specialist from the deep brain stimulation program at The Ottawa Hospital, Civic Campus * to undergo pre-operative MRI with contrast |
| Control group | – | –* patients diagnosed with either essential tremor or cervical dystonia by a movement disorder specialist from the deep brain stimulation program at The Ottawa Hospital, Civic Campus * to undergo pre-operative MRI with contrast |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients having movement disorders undergoing deep brain stimulation (DBS) of the internal segment of the globus pallidus for treatment of motor symptoms refractory to medical therapy at the Ottawa Hospital, Civic Campus, will be recruited to participate in this pilot study. The cohort will include 10 PD patients and 10 control subjects. The PD subjects will have received a diagnosis of PD using established clinical criteria following clinical assessment at the Movement Disorders Clinic of The Ottawa Hospital. The 10 control subjects will consist of those undergoing DBS and assessed in the same clinic with a clinical diagnosis of either essential tremor or cervical dystonia.
Key inclusion criteria (8 listed)
- Disease burden is dominated by motor symptoms such as rigidity, bradykinesia, akinesia, and tremor;
- Medications have been optimized by a movement disorder neurologist;
- Adequate social support to assist with preoperative recovery and problems during subsequent programming;
- No major mood disorder and any mood disorders are medically optimized;
- No major cognitive impairment;
Key exclusion criteria (8 listed)
- Disease burden is not dominated by motor symptoms such as rigidity, bradykinesia, akinesia, and tremor;
- Medications have not bee optimized by a movement disorder neurologist;
- There is not adequate social support to assist with pre-operative recovery or problems during subsequent programming;
- Presence of major mood disorders or any mood disorders not medically optimized;
- Presence of major cognitive impairment;
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
Degree of contrast enhancement
Time frame: one year
Pre-contrast images will be used as mask images and will be digitally substracted from post-contrast images to obtain the "difference" images. From the "difference images", two neuroradiologists blinded to the clinical status of the patient will assess the degree enhancement in the striatum (none,mild, moderate, marked).
1 secondary outcome
Permeability of blood brain barrier in the striatum
Time frame: one year
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 31 Dec 2020.
- Background: PubMed 12666095Warner TT, Schapira AH. Genetic and environmental factors in the cause of Parkinson's disease. Ann Neurol. 2003;53 Suppl 3:S16-23; discussion S23-5. doi: 10.1002/ana.10487.
- Background: PubMed 25757748Gray MT, Woulfe JM. Striatal blood-brain barrier permeability in Parkinson's disease. J Cereb Blood Flow Metab. 2015 May;35(5):747-50. doi: 10.1038/jcbfm.2015.32. Epub 2015 Mar 11.
- Background: PubMed 20563819Schulz-Schaeffer WJ. The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia. Acta Neuropathol. 2010 Aug;120(2):131-43. doi: 10.1007/s00401-010-0711-0. Epub 2010 Jun 20.
- Background: PubMed 16219675Orr CF, Rowe DB, Mizuno Y, Mori H, Halliday GM. A possible role for humoral immunity in the pathogenesis of Parkinson's disease. Brain. 2005 Nov;128(Pt 11):2665-74. doi: 10.1093/brain/awh625. Epub 2005 Oct 11.
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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.
Thanh B Nguyen, MD, FRCP principal investigator
The Ottawa Hospital
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 Movement Disorders, run by Ottawa Hospital Research Institute 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 8 inclusion and 8 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 31 Dec 2020. 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?
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?
Degree of contrast enhancement (time frame: one year). 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 NCT02605161, 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 31 Dec 2020.