Microvascular DiseaseSVATNCT06624267
Test of Reproducibility of [15O]H20-PET Assessment of Brain Perfusion
An observational study of Microvascular Disease and Microvascular Complications, run by University Hospital Bispebjerg and Frederiksberg at 1 site in Denmark.
Trial summary
In the aging population, ischemic heart disease, stroke and dementia are increasingly prevalent. Diagnosis and treatment of the former two i.e., large-vessel coronary heart disease and endovascular thrombectomy of the brain in relation to stroke have improved significantly. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Microvascular Disease, Microvascular Complications, Diabetes Mellitus Type 2
- What is being tested?
- PET
- Type of treatment
- Injection or infusion
- How many people
- 8 participants
- Where
- 1 siteDenmark
- Study dates
- Nov 2024to Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy participants \>60 years.
Who may be able to join
- Age \> 60 years
- No diagnosis of T2D according to WHO\'s criteria.
- Speaks and understands Danish (required for reliable cognitive testing)
- Able to provide informed and written consent
Who cannot join
- Moderate to high intensity training \>2 times/week.
- Previous AMI, atrial fibrillation, significant cardiac valve disease, HFrEF (LVEF \<45%), asthma.
- Previous stroke or significant neurological disease including cognitive dysfunction.
- Ongoing depression.
- Hypothyroidism
- Unable or unwilling to participate in training, e.g., due to injury, arthrosis or lung disease.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site
Bispebjerg and Frederiksberg Hospital
Copenhagen, 2400
Anita L. Chief Biomedical Laboratory Scientist, Bachelor's Degree, +4521381056, anita.larsen.01@regionh.dk
Thomas J. Primary Investigator, Medical doctor, +4551903442, thomasehlighjermindjustesen@regionh.dk
About this study
Official title: Small Vessel Disease of the Brain and Heart: a Perfusion PET Study of Training Effects
In the aging population, ischemic heart disease, stroke and dementia are increasingly prevalent. Diagnosis and treatment of the former two i.e., large-vessel coronary heart disease and endovascular thrombectomy of the brain in relation to stroke have improved significantly. Yet, the majority of elderly patients with ischemic heart disease do not have large-vessel heart disease and it seems that small vessel disease (SVD) may explain a large fraction of these cases as well as the cardiovascular morbidity in the elderly. Hence, the current development in diagnostics and treatments of ischemic heart disease does not address the most common subtype of ischemic disease seen in elderly patients.
It has been suggested that SVD is part of a multisystem disorder and several systematic reviews have addressed the hypothesis of a potential link between small vessel disease of the heart, brain, and kidneys. Cerebral SVD is prevalent in the aging population causing cognitive impairment, dementia, and an increased risk of stroke, and cerebral hypoperfusion is an acknowledged cause of vascular dementia and a possible cause of Alzheimer's disease. Further, cognitive impairment within multiple cognitive domains is highly prevalent in heart failure and is associated to an increased risk of dementia. The link between heart failure and dementia may be due to multisystem SVD, although a direct link between the two is possible.
Read more
Among other known risk factors such as age, hypertension, and female sex, diabetes is a major cause of SVD and is linked to coronary heart disease as well as cognitive impairment. The diagnosis of cerebral SVD relies on MRI detecting infarctions, haemorrhages, microbleeds and ischemic white matter changes, i.e. Fazekas score. In contrast, perfusion PET is used to image myocardial perfusion in patients with coronary SVD; and coronary SVD is recognized as a part of the pathophysiology in angina, coronary artery disease, and heart failure. Perfusion PET before and after adenosine-induced vasodilation allows for measuring, the myocardial flow reserve (MFR), i.e. perfusion capacity, which in the absence of regional perfusion defects, is a measure of coronary SVD. Prof. Eva Prescott have recently shown that reduced MFR obtained by 82Rb PET is a strong predictor of future microvascular events and all-cause mortality.
Exercise is well known to improve cognitive health but professor Carl-Johan Boraxbekk has shown that the effect on cognitive performance may be dependent on the initial cerebrovascular status, as patients with moderate to severe white matter changes did not improve after a 6 months physical activation intervention in contrast to patients with mild changes. Yet, it is possible to improve brain function in diabetic patients through either dietary or exercise interventions.
Systemic SVD is measured as cerebral SVD (reduced brain perfusion during acetazolamide-induced vasodilation) and coronary SVD (reduced heart perfusion during adenosine-induced vasodilation). The researchers anticipate that patients with type 2 dabetes have reduced perfusion capacity of the brain and heart correlating to reduced cognition and cardiorespiratory fitness (VO2-max).
Read the detailed description
The researchers wish to test how large the variance of their measurements of blood perfusion to the brain is in healthy participants when performing 2 identical examinations within 7 days of each other.
To adress this aim the researchers have defined the following assumption that they will refute or confirm through their study:
- PET-perfusion measurements at their department have a high reproducibility.
8 healthy participants over 60 years will undergo a [15O]H2O-PET scan in order to assess the blood perfusion capacity of the brain.
Within 7 days, the 8 healthy participants will undergo an additional [15O]H2O-PET scan assessing the blood perfusion capacity of the brain.
Afterwards the researchers will quantify the variance in their [15O]H2O-PET scan in the same individuals within a 7-day time window.
- Conditions
- Microvascular Disease, Microvascular Complications, Diabetes Mellitus Type 2, Cerebral Hypoperfusion, Dementia
- Being tested
- PET
- Keywords
- microvascular disease, microvascular complications of the heart, microvascular complications of the brain, microvascular disease patophysiology, diabetes type 2, dementia
- Medical subject headings
- Diabetes Mellitus, Type 2, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PETDiagnostic test
PET imaging will be performed with a Discovery 710 PET/CT scanner (GE Healthcare, Milwaukee, WI, USA). Two 5-minute PET recordings will be performed of each subject within a single scanning session of 70 min. One 5-minute scan is conducted of the brain in rest. [15O]H2O, is produced on-site (GENtrace, GE, Uppsala, Sweden), and 600 MBq [15O]H2O is intravenously injected by an automatic Hidex Radiowater Generator (Hidex, Turku, Finland). To induce brain vasodilation, 1 g of acetazolamide is infused over 5 min and 15 min later the brain is scanned. Cerebral perfusion is calculated using PMOD software (PMOD Technologies, Switzerland).
| Study group | Role | What they receive |
|---|---|---|
| 24 healthy participants over 60 years | Baseline measurements of: -[15O]H2O PET of the brain Receives: Diagnostic Test: PET |
What is being measured
The primary outcome is the main question the study is designed to answer.
[15O]H2O PET assessment of the blood perfusion of the brain
We will use the scan to determine our primary outcome: Blood perfusion to the heart and brain.
Radioactive water ([15O]H2O) will be used as a PET-tracer since it follows the blood and is the gold standard tracer for PET-based blood perfusion measurements.
We measure the blood perfusion of the brain as the perfusion capacity, meaning the difference between blood perfusion to the organ at rest and the maximally possible perfusion. In the brain we use injection of diamox to stimualte maximal dilation of the cerebral arteries which corresponds to the maximally possible perfusion of the brain.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2024
- Study startNov 2024 (estimated)
- Primary completionJan 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Microvascular 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
- Other
- Time perspective
- Prospective
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Bispebjerg and Frederiksberg
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Cardiovascular Academy, Bispebjerg Hospital, The Dagmar Marshall Foundation, Steno Diabetes Center Copenhagen
- Responsible party
- Principal investigator, Thomas Ehlig Hjermind Justesen, University Hospital Bispebjerg and Frederiksberg
- Investigators
- Thomas EHJ Primary Investigator, Medical Doctor, Principal investigator, University Hospital Bispebjerg and Frederiksberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06624267
- Sponsor's protocol ID
- H-24052476
- Other IDs
- PhD2024013-HF
- Acronym
- SVAT
- Status last verified
- Oct 2024
- First submitted
- 30 Sep 2024
- Last updated
- 4 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Have not gotten the necessary clearence
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Small Vessel Disease of the Brain and Heart: a Perfusion PET Study of Training Effects
- ClinicalTrials.gov ID
- NCT06624267
- Acronym / sponsor ID
- SVAT / H-24052476
- Conditions
- Microvascular Disease, Microvascular Complications, Diabetes Mellitus Type 2, Cerebral Hypoperfusion, Dementia
- Keywords
- microvascular disease, microvascular complications of the heart, microvascular complications of the brain, microvascular disease patophysiology, diabetes type 2, dementia
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- University Hospital Bispebjerg and FrederiksbergUniversity, hospital or other
- Collaborators
- Danish Cardiovascular Academy, Bispebjerg Hospital, The Dagmar Marshall Foundation, Steno Diabetes Center Copenhagen
- Study start
- Nov 2024 (estimated)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 2 Oct 2024 (actual)
- 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.
In the aging population, ischemic heart disease, stroke and dementia are increasingly prevalent. Diagnosis and treatment of the former two i.e., large-vessel coronary heart disease and endovascular thrombectomy of the brain in relation to stroke have improved significantly. Yet, the majority of elderly patients with ischemic heart disease do not have large-vessel heart disease and it seems that small vessel disease (SVD) may explain a large fraction of these cases as well as the cardiovascular morbidity in the elderly. Hence, the current development in diagnostics and treatments of ischemic heart disease does not address the most common subtype of ischemic disease seen in elderly patients.
It has been suggested that SVD is part of a multisystem disorder and several systematic reviews have addressed the hypothesis of a potential link between small vessel disease of the heart, brain, and kidneys. Cerebral SVD is prevalent in the aging population causing cognitive impairment, dementia, and an increased risk of stroke, and cerebral hypoperfusion is an acknowledged cause of vascular dementia and a possible cause of Alzheimer's disease. Further, cognitive impairment within multiple cognitive domains is highly prevalent in heart failure and is associated to an increased risk of dementia. The link between heart failure and dementia may be due to multisystem SVD, although a direct link between the two is possible.
Among other known risk factors such as age, hypertension, and female sex, diabetes is a major cause of SVD and is linked to coronary heart disease as well as cognitive impairment. The diagnosis of cerebral SVD relies on MRI detecting infarctions, haemorrhages, microbleeds and ischemic white matter changes, i.e. Fazekas score. In contrast, perfusion PET is used to image myocardial perfusion in patients with coronary SVD; and coronary SVD is recognized as a part of the pathophysiology in angina, coronary artery disease, and heart failure. Perfusion PET before and after adenosine-induced vasodilation allows for measuring, the myocardial flow reserve (MFR), i.e. perfusion capacity, which in the absence of regional perfusion defects, is a measure of coronary SVD. Prof. Eva Prescott have recently shown that reduced MFR obtained by 82Rb PET is a strong predictor of future microvascular events and all-cause mortality.
Exercise is well known to improve cognitive health but professor Carl-Johan Boraxbekk has shown that the effect on cognitive performance may be dependent on the initial cerebrovascular status, as patients with moderate to severe white matter changes did not improve after a 6 months physical activation intervention in contrast to patients with mild changes. Yet, it is possible to improve brain function in diabetic patients through either dietary or exercise interventions.
Systemic SVD is measured as cerebral SVD (reduced brain perfusion during acetazolamide-induced vasodilation) and coronary SVD (reduced heart perfusion during adenosine-induced vasodilation). The researchers anticipate that patients with type 2 dabetes have reduced perfusion capacity of the brain and heart correlating to reduced cognition and cardiorespiratory fitness (VO2-max).
Detailed description
The researchers wish to test how large the variance of their measurements of blood perfusion to the brain is in healthy participants when performing 2 identical examinations within 7 days of each other.
To adress this aim the researchers have defined the following assumption that they will refute or confirm through their study:
- PET-perfusion measurements at their department have a high reproducibility.
8 healthy participants over 60 years will undergo a [15O]H2O-PET scan in order to assess the blood perfusion capacity of the brain.
Within 7 days, the 8 healthy participants will undergo an additional [15O]H2O-PET scan assessing the blood perfusion capacity of the brain.
Afterwards the researchers will quantify the variance in their [15O]H2O-PET scan in the same individuals within a 7-day time window.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 24 healthy participants over 60 years | – | Diagnostic Test: PETBaseline measurements of: -[15O]H2O PET of the brain |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy participants \>60 years.
Key inclusion criteria (4 listed)
- Age \> 60 years
- No diagnosis of T2D according to WHO\'s criteria.
- Speaks and understands Danish (required for reliable cognitive testing)
- Able to provide informed and written consent
Key exclusion criteria (6 listed)
- Moderate to high intensity training \>2 times/week.
- Previous AMI, atrial fibrillation, significant cardiac valve disease, HFrEF (LVEF \<45%), asthma.
- Previous stroke or significant neurological disease including cognitive dysfunction.
- Ongoing depression.
- Hypothyroidism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PETPET imaging will be performed with a Discovery 710 PET/CT scanner (GE Healthcare, Milwaukee, WI, USA). Two 5-minute PET recordings will be performed of each subject within a single scanning session of 70 min. One 5-minute scan is conducted of the brain in rest. [15O]H2O, is produced on-site (GENtrace, GE, Uppsala, Sweden), and 600 MBq [15O]H2O is intravenously injected by an automatic Hidex Radiowater Generator (Hidex, Turku, Finland). To induce brain vasodilation, 1 g of acetazolamide is infused over 5 min and 15 min later the brain is scanned. Cerebral perfusion is calculated using PMOD software (PMOD Technologies, Switzerland). | Diagnostic test | 24 healthy participants over 60 years |
Primary outcome
[15O]H2O PET assessment of the blood perfusion of the brain
Time frame: 2 years
We will use the scan to determine our primary outcome: Blood perfusion to the heart and brain. Radioactive water ([15O]H2O) will be used as a PET-tracer since it follows the blood and is the gold standard tracer for PET-based blood perfusion measurements. We measure the blood perfusion of the brain as the perfusion capacity, meaning the difference between blood perfusion to the organ at rest and the maximally possible perfusion. In the brain we use injection of diamox to stimualte maximal dilation of the cerebral arteries which corresponds to the maximally possible perfusion of the brain.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2024.
- Individual participant dataSharing planned: No. Have not gotten the necessary clearence
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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.
Thomas EHJ Primary Investigator, Medical Doctor principal investigator
University Hospital Bispebjerg and Frederiksberg
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 Microvascular Disease and Microvascular Complications, run by University Hospital Bispebjerg and Frederiksberg at 1 site in Denmark.
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 6 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: opening soon, as of the sponsor's last update on 4 Oct 2024. 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 Denmark. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Primary Investigator, Medical Doctor (4551903442, thomasehlighjermindjustesen@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
[15O]H2O PET assessment of the blood perfusion of the brain (time frame: 2 years). 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 4 Oct 2024; AzTrials last refreshed its copy on 8 Nov 2026.