CadasilNCT05902039
MRI Study of Blood-brain Barrier Function in CADASIL
An observational study of Cadasil and Blood Brain Barrier Defect, run by Peking University First Hospital at 1 site in China.
Trial summary
Diffusion prepared pseudo-continuous ASL (DP-pCASL) is a newly proposed MRI method to noninvasively measure the function of blood-brain barrier (BBB). The investigators aim to investigate whether the water exchange rate across the BBB, estimated with DP-pCASL, is changed in patients with CADASIL, and to analyze the… Read more about this study
- Who is it for?
- Ages 20 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Cadasil, Blood Brain Barrier Defect
- What is being tested?
- MRI
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2021to 1 Apr 2026
- 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 20 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: All CADASIL patients and controls who met the criteria described below and who agreed to participate in this study were enrolled. All CADASIL patients included in this study have been visited at Peking University First Hospital, and the included controls were recruited from the community.
Who may be able to join
- Patients with CADASIL confirmed by gene or/and skin biopsy.
- The age range is 20-70 years old.
- There is no contraindication to MRI examination, and the informed consent is signed.
Who cannot join
- Combined with definite cerebrovascular disease, or combined with brain tumor, brain trauma and other causes of brain diseases.
- CADASIL is not confirmed.
- There are contraindications to examination or refusal to sign the informed consent.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking University First Hospital
Beijing
Chen Ling, PhD, +86 18101358135, lnyy.chen@foxmail.com
About this study
Diffusion prepared pseudo-continuous ASL (DP-pCASL) is a newly proposed MRI method to noninvasively measure the function of blood-brain barrier (BBB). The investigators aim to investigate whether the water exchange rate across the BBB, estimated with DP-pCASL, is changed in patients with CADASIL, and to analyze the association between BBB water exchange rate and MRI/clinical features in these patients.
Read the detailed description
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by NOTCH3 gene mutations, is the most frequent monogenic type of hereditary cerebral small vessel disease (CSVD). The unique pathophysiological mechanisms that small vessel disorders in CADASIL are caused by genetic mutations and that the majority of patients do not combine cerebrovascular disease risk factors make CADASIL an ideal model for studying CSVD, and the imaging findings on CADASIL can be used to diagnose and investigate the etiology of CSVD. While abnormalities in the cerebrovascular structure and hemodynamics have been well demonstrated in CADASIL, the abnormality of the BBB remains controversial. One DCE-MRI study suggested an increase in BBB permeability to gadolinium contrast in CADASIL, whereas no abnormality of BBB was found in subsequent studies in mouse models and patients. The aim of this study was to assess whether BBB function is abnormal in patients with CADASIL using DP-pCASL, which is more sensitive to subtle changes in the BBB compared to DCE-MRI. The investigators hypothesized that the BBB water exchange rate (kw) is reduced in patients with CADASIL compared to controls as assessed by DP-pCASL and that the degree of reduction in BBB water exchange rate correlates with the severity of disease in patients with CADASIL.
- Conditions
- Cadasil, Blood Brain Barrier Defect
- Being tested
- MRI
- Medical subject headings
- CADASIL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIOther
Also called Cognitive Scale and Clinical Scale Evaluation
All participants underwent an MR examination on a 3T whole-body Prisma MRI system (Siemens, Erlangen, Germany) with a 64-channel head coil, and a 7T whole-body MAGNETOM MR system (Siemens, Erlangen, Germany) using a 32-channel receive/birdcage transmit head coil (NOVA medical). DP-pCASL, Multi-delay pCASL (MD-pCASL) was acquired to evaluate BBB function and cerebral perfusion. T1-weighted magnetization-prepared rapid gradient echo (T1w-MPRAGE) was scanned at both 3T and 7T for registration in the post-processing workflow. T2-weighted fluid-attenuated inversion recovery (T2w-FLAIR) and T2*-weighted gradient echo (T2*w-GRE) were acquired at 7T for high-resolution structural images and evaluation of lesions.
| Study group | Role | What they receive |
|---|---|---|
| CADASIL patients | Inclusion Criteria:
1. Patients with CADASIL confirmed by gene or/and skin biopsy.
2. The age range is 20-70 years old.
3. There is no contraindication to MRI examination, and the informed consent is signed.
exclusion criteria：
1. Combined with definite cerebrovascular disease, or combined with brain tumor, brain trauma and other causes of brain diseases.
2. CADASIL is not confirmed.
3. There are contraindications to examination or refusal to sign the informed consent. Receives: Other: MRI | |
| Healthy controls | Inclusion Criteria: 1. The age range is 20-70 years old. 2. There is no contraindication to MRI examination, and the informed consent is signed. exclusion criteria： 1. Combined with definite cerebrovascular disease, or combined with brain tumor, brain trauma and other causes of brain diseases. 2. There are contraindications to examination or refusal to sign the informed consent. |
What is being measured
The primary outcome is the main question the study is designed to answer.
kw
Post-processing of DP-pCASL data was performed offline using LOFT BBB Toolbox. Head motion was corrected using SPM12 and the temporal fluctuations were minimized by using principal component analysis. DP-pCASL data with the b value of 50 s/mm2 were used to obtain the ASL signal from the tissue and capillary compartments respectively, and kw was quantified by using a single-pass approximation model with total generalized variation regularization.
Measured: 30 Minutes
Secondary outcomes (3)
CBF
Post-processing of MD-pCASL data was performed offline using the BASIL toolkit of FSL. Cerebral blood flow (CBF) were calculated by a custom script using the BASIL toolkit of FSL.
Measured: 30 Minutes
ATT
Post-processing of MD-pCASL data was performed offline using the BASIL toolkit of FSL. Arterial transit time (ATT) were calculated by a custom script using the BASIL toolkit of FSL.
Measured: 30 Minutes
QSM
QSM image reconstruction, including phase pre-processing and estimation of susceptibility maps, followed the default QSMbox (https:// gitlab. com/ acostaj/ QSMbox) pipeline for single-echo, coil-combined data.
Measured: 30 Minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2023
- Study start1 Apr 2021
- Primary completion1 Apr 2025 (estimated)
- Study completion1 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for CadasilStudies 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
- Cross-sectional
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University First Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Chinese Academy of Sciences
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05902039
- Sponsor's protocol ID
- 2022-715
- Status last verified
- Jun 2023
- First submitted
- 21 Apr 2023
- Last updated
- 13 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
St Lawrence KS, Owen D, Wang DJ. A two-stage approach for measuring vascular water exchange and arterial transit time by diffusion-weighted perfusion MRI. Magn Reson Med. 2012 May;67(5):1275-84. doi: 10.1002/mrm.23104. Epub 2011 Aug 19.
PubMed 21858870Shao X, Ma SJ, Casey M, D'Orazio L, Ringman JM, Wang DJJ. Mapping water exchange across the blood-brain barrier using 3D diffusion-prepared arterial spin labeled perfusion MRI. Magn Reson Med. 2019 May;81(5):3065-3079. doi: 10.1002/mrm.27632. Epub 2018 Dec 18.
PubMed 30561821Uchida Y, Kan H, Sakurai K, Arai N, Inui S, Kobayashi S, Kato D, Ueki Y, Matsukawa N. Iron leakage owing to blood-brain barrier disruption in small vessel disease CADASIL. Neurology. 2020 Sep 1;95(9):e1188-e1198. doi: 10.1212/WNL.0000000000010148. Epub 2020 Jun 25.
PubMed 32586899Walsh J, Tozer DJ, Sari H, Hong YT, Drazyk A, Williams G, Shah NJ, O'Brien JT, Aigbirhio FI, Rosenberg G, Fryer TD, Markus HS. Microglial activation and blood-brain barrier permeability in cerebral small vessel disease. Brain. 2021 Jun 22;144(5):1361-1371. doi: 10.1093/brain/awab003.
PubMed 34000009Sun C, Wu Y, Ling C, Xie Z, Sun Y, Xie Z, Li Z, Fang X, Kong Q, An J, Wang B, Zhuo Y, Zhang W, Wang Z, Yuan Y, Zhang Z. Reduced blood flow velocity in lenticulostriate arteries of patients with CADASIL assessed by PC-MRA at 7T. J Neurol Neurosurg Psychiatry. 2022 Apr;93(4):451-452. doi: 10.1136/jnnp-2021-326258. Epub 2021 Sep 28. No abstract available.
PubMed 34583945Li Y, Ying Y, Yao T, Jia X, Liang H, Tang W, Jia X, Song H, Shao X, Wang DJJ, Wang C, Cheng X, Yang Q. Decreased water exchange rate across blood-brain barrier in hereditary cerebral small vessel disease. Brain. 2023 Jul 3;146(7):3079-3087. doi: 10.1093/brain/awac500.
PubMed 36625892Li Z, Sun D, Ling C, Bai L, Zhang J, Wu Y, Yuan Y, Wang Z, Wang Z, Zhuo Y, Xue R, Zhang Z. Quantitative modeling of lenticulostriate arteries on 7-T TOF-MRA for cerebral small vessel disease. Eur Radiol Exp. 2024 Nov 5;8(1):126. doi: 10.1186/s41747-024-00512-7.
PubMed 39499373
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MRI Study of Blood-brain Barrier Function in CADASIL
- ClinicalTrials.gov ID
- NCT05902039
- Acronym / sponsor ID
- 2022-715
- Conditions
- Cadasil, Blood Brain Barrier Defect
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Peking University First HospitalUniversity, hospital or other
- Collaborators
- Chinese Academy of Sciences
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 1 Apr 2025 (estimated)
- Study completion
- 1 Apr 2026 (estimated)
- First posted
- 13 Jun 2023 (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.
Diffusion prepared pseudo-continuous ASL (DP-pCASL) is a newly proposed MRI method to noninvasively measure the function of blood-brain barrier (BBB). The investigators aim to investigate whether the water exchange rate across the BBB, estimated with DP-pCASL, is changed in patients with CADASIL, and to analyze the association between BBB water exchange rate and MRI/clinical features in these patients.
Detailed description
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by NOTCH3 gene mutations, is the most frequent monogenic type of hereditary cerebral small vessel disease (CSVD). The unique pathophysiological mechanisms that small vessel disorders in CADASIL are caused by genetic mutations and that the majority of patients do not combine cerebrovascular disease risk factors make CADASIL an ideal model for studying CSVD, and the imaging findings on CADASIL can be used to diagnose and investigate the etiology of CSVD. While abnormalities in the cerebrovascular structure and hemodynamics have been well demonstrated in CADASIL, the abnormality of the BBB remains controversial. One DCE-MRI study suggested an increase in BBB permeability to gadolinium contrast in CADASIL, whereas no abnormality of BBB was found in subsequent studies in mouse models and patients. The aim of this study was to assess whether BBB function is abnormal in patients with CADASIL using DP-pCASL, which is more sensitive to subtle changes in the BBB compared to DCE-MRI. The investigators hypothesized that the BBB water exchange rate (kw) is reduced in patients with CADASIL compared to controls as assessed by DP-pCASL and that the degree of reduction in BBB water exchange rate correlates with the severity of disease in patients with CADASIL.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CADASIL patients | – | Other: MRIInclusion Criteria: 1. Patients with CADASIL confirmed by gene or/and skin biopsy. 2. The age range is 20-70 years old. 3. There is no contraindication to MRI examination, and the informed consent is signed. exclusion criteria： 1. Combined with definite cerebrovascular disease, or combined with brain tumor, brain trauma and other causes of brain diseases. 2. CADASIL is not confirmed. 3. There are contraindications to examination or refusal to sign the informed consent. |
| Healthy controls | – | –Inclusion Criteria: 1. The age range is 20-70 years old. 2. There is no contraindication to MRI examination, and the informed consent is signed. exclusion criteria： 1. Combined with definite cerebrovascular disease, or combined with brain tumor, brain trauma and other causes of brain diseases. 2. There are contraindications to examination or refusal to sign the informed consent. |
Who may qualify
- Ages
- 20 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- All CADASIL patients and controls who met the criteria described below and who agreed to participate in this study were enrolled. All CADASIL patients included in this study have been visited at Peking University First Hospital, and the included controls were recruited from the community.
Key inclusion criteria (3 listed)
- Patients with CADASIL confirmed by gene or/and skin biopsy.
- The age range is 20-70 years old.
- There is no contraindication to MRI examination, and the informed consent is signed.
Key exclusion criteria (3 listed)
- Combined with definite cerebrovascular disease, or combined with brain tumor, brain trauma and other causes of brain diseases.
- CADASIL is not confirmed.
- There are contraindications to examination or refusal to sign the informed consent.
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 |
|---|---|---|
| MRIAlso: Cognitive Scale and Clinical Scale EvaluationAll participants underwent an MR examination on a 3T whole-body Prisma MRI system (Siemens, Erlangen, Germany) with a 64-channel head coil, and a 7T whole-body MAGNETOM MR system (Siemens, Erlangen, Germany) using a 32-channel receive/birdcage transmit head coil (NOVA medical). DP-pCASL, Multi-delay pCASL (MD-pCASL) was acquired to evaluate BBB function and cerebral perfusion. T1-weighted magnetization-prepared rapid gradient echo (T1w-MPRAGE) was scanned at both 3T and 7T for registration in the post-processing workflow. T2-weighted fluid-attenuated inversion recovery (T2w-FLAIR) and T2*-weighted gradient echo (T2*w-GRE) were acquired at 7T for high-resolution structural images and evaluation of lesions. | Other | CADASIL patients |
Primary outcome
kw
Time frame: 30 Minutes
Post-processing of DP-pCASL data was performed offline using LOFT BBB Toolbox. Head motion was corrected using SPM12 and the temporal fluctuations were minimized by using principal component analysis. DP-pCASL data with the b value of 50 s/mm2 were used to obtain the ASL signal from the tissue and capillary compartments respectively, and kw was quantified by using a single-pass approximation model with total generalized variation regularization.
3 secondary outcomes
CBF
Time frame: 30 Minutes
ATT
Time frame: 30 Minutes
QSM
Time frame: 30 Minutes
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2023.
- Background: PubMed 21858870St Lawrence KS, Owen D, Wang DJ. A two-stage approach for measuring vascular water exchange and arterial transit time by diffusion-weighted perfusion MRI. Magn Reson Med. 2012 May;67(5):1275-84. doi: 10.1002/mrm.23104. Epub 2011 Aug 19.
- Background: PubMed 30561821Shao X, Ma SJ, Casey M, D'Orazio L, Ringman JM, Wang DJJ. Mapping water exchange across the blood-brain barrier using 3D diffusion-prepared arterial spin labeled perfusion MRI. Magn Reson Med. 2019 May;81(5):3065-3079. doi: 10.1002/mrm.27632. Epub 2018 Dec 18.
- Background: PubMed 32586899Uchida Y, Kan H, Sakurai K, Arai N, Inui S, Kobayashi S, Kato D, Ueki Y, Matsukawa N. Iron leakage owing to blood-brain barrier disruption in small vessel disease CADASIL. Neurology. 2020 Sep 1;95(9):e1188-e1198. doi: 10.1212/WNL.0000000000010148. Epub 2020 Jun 25.
- Background: PubMed 34000009Walsh J, Tozer DJ, Sari H, Hong YT, Drazyk A, Williams G, Shah NJ, O'Brien JT, Aigbirhio FI, Rosenberg G, Fryer TD, Markus HS. Microglial activation and blood-brain barrier permeability in cerebral small vessel disease. Brain. 2021 Jun 22;144(5):1361-1371. doi: 10.1093/brain/awab003.
- Background: PubMed 34583945Sun C, Wu Y, Ling C, Xie Z, Sun Y, Xie Z, Li Z, Fang X, Kong Q, An J, Wang B, Zhuo Y, Zhang W, Wang Z, Yuan Y, Zhang Z. Reduced blood flow velocity in lenticulostriate arteries of patients with CADASIL assessed by PC-MRA at 7T. J Neurol Neurosurg Psychiatry. 2022 Apr;93(4):451-452. doi: 10.1136/jnnp-2021-326258. Epub 2021 Sep 28. No abstract available.
- Background: PubMed 36625892Li Y, Ying Y, Yao T, Jia X, Liang H, Tang W, Jia X, Song H, Shao X, Wang DJJ, Wang C, Cheng X, Yang Q. Decreased water exchange rate across blood-brain barrier in hereditary cerebral small vessel disease. Brain. 2023 Jul 3;146(7):3079-3087. doi: 10.1093/brain/awac500.
- Derived from this study: PubMed 39499373Li Z, Sun D, Ling C, Bai L, Zhang J, Wu Y, Yuan Y, Wang Z, Wang Z, Zhuo Y, Xue R, Zhang Z. Quantitative modeling of lenticulostriate arteries on 7-T TOF-MRA for cerebral small vessel disease. Eur Radiol Exp. 2024 Nov 5;8(1):126. doi: 10.1186/s41747-024-00512-7.
- Individual participant dataSharing planned: No
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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.
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 Cadasil and Blood Brain Barrier Defect, run by Peking University First Hospital at 1 site in China.
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 3 inclusion and 3 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 13 Jun 2023. 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 China. 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?
Contact Chen Ling, PhD (+86 18101358135, lnyy.chen@foxmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
kw (time frame: 30 Minutes). 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 NCT05902039, which also lists 7 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 13 Jun 2023.