CadasilPhase 2AMCADNCT06072118
Adrenomedullin for CADASIL
A Phase 2 study testing Adrenomedullin in people with Cadasil, run by National Cerebral and Cardiovascular Center, Japan at 1 site in Japan.
Trial summary
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary cerebral small vessel disease, with no proven disease-modifying treatments. Read more about this study
- Who is it for?
- Ages 20 to 90 years
- Conditions the study is for
- Cadasil
- What is being tested?
- Adrenomedullin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteJapan
- Study dates
- 6 Jan 2022to 12 Jun 2023
- Phase
- Phase 2
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who have given written informed consent from the patient or the sponsor to participate in the clinical trial
- Patients aged between 20 and 90 at the time of obtaining consent
- Patients diagnosed as CADASIL after confirming NOTCH3 gene mutation by genetic testing
- Patients with Mini-mental state examination-J score of 10-27 or Trail maiking test score (age ajustment) of average + 1.5 SD (standard deviation) or higher
Who cannot join
- Patients who cannot perform cognitive function tests (deafness, blindness, etc., MMSE-J less than 10 points Severe cognitive impairment, etc.)
- Patients received reatment with prohibited drugs or prohibited therapy within the past 12 weeks from the time of registration
- Patients who started to take concomitant restriction drugs or changed dosage of concomitant restriction drugs within the past 4 weeks from the time of registration
- Patients whose Mini-mental state examination-J with 4 or more points improvements between the time of registration and 4 weeks or more at the time of screening (If patients who take concomitant restriction drugs)
- Patients with active infections requiring antibiotic treatment at registration
- Patients with a disability equivalent to modified Rankin Scale 5 at registration
Show all 21Show fewer
- Patients with severe consciousness impairment (Japan Coma Scale 100 or more)
- Patients with severe renal impairment (estimated GFR less than 30 mL / min / 1.73m2) at registration
- Patients with severe liver damage (transaminase AST (GOT) or ALT (GPT) 100 IU / L or more) at registration
- Patients diagnosed as having cerebral infarction or intracranial hemorrhage or transient ischemic attack or cerebral aneurysm with high probability of rupture within the last 12 weeks from the time of registration
- Patients with occlusion or severe stenosis of the intracranial main artery or carotid artery at the time of registration
- Patients with significant ECG abnormalities (atrioventricular block of 2-3 degrees, extension of QRS interval of 120 ms or more, extension of QTcB of 450 msec or more) at registration, or past histroy of acute coronary syndrome or acute heart failure within the last 12 weeks from the time of registration
- Patients with systolic blood pressure less than 100 mmHg at registration
- Patients whose pulse rate is less than 45 beats / minute or 120 beats / minute or more at registration
- Patients with substance abuse or alcoholism
- Patients who cannot perform MRI
- Patients with active solid malignant tumors
- Patients who do not give consent to contraception from the date of obtaining consent until the end of the safety evaluation period
- Pregnant, lactating, and possibly pregnant
- Patient who participated in another trial within 24 weeks before registration
- Other patients judged by the Investigator or Investigator to be ineligible for this study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicenter, Single-arm, Clinical Trial of Adrenomedullin for Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary cerebral small vessel disease, with no proven disease-modifying treatments. Adrenomedullin, a vasoactive peptide, has angiogenic, vasodilation, anti-inflammatory, and anti-oxidative properties and could have triple sites of action on components of the neuro-glial-vascular unit consisting of vessels, microglia and oligodendrocytes or, more specifically, on the white matter oligovascular unit. The aim of the AMCAD trial is to assess the safety and efficacy of Adrenomedullin in CADASIL patients.
- Conditions
- Cadasil
- Being tested
- Adrenomedullin
- Medical subject headings
- CADASIL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdrenomedullinDrug
Dosing at 15 ng/kg/min for 8 hours is continued for 14 days.
| Study group | Role | What they receive |
|---|---|---|
| Adrenomedullin group | Experimental | Not described Receives: Drug: Adrenomedullin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral blood flow change rate evaluated by arterial spin labeling
Frontal lobe
Measured: at 28 days post adrenomedullin administration
Secondary outcomes (10)
Cerebral blood flow change rate evaluated by arterial spin labeling
Frontal lobe
Measured: at 8 hours / 15 days / 90 days / 180 days post adrenomedullin administration
Cerebral blood flow change rate evaluated by arterial spin labeling
Whole brain mean and each area
Measured: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Mean diffusivity change rate of the white matter evaluated by MR diffusion tensor imaging
Whole brain mean and each area
Measured: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Fractional anisotropy change rate of the white matter evaluated by MR diffusion tensor imaging
Whole brain mean and each area
Measured: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Change in times of Trail making test-A/B from baseline evaluation
Measured: at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Change in scores of Montreal cognitive assessment from baseline evaluation
Measured: at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Change in scores of Wechsler Adult Intelligence Scale-Fourth edition from baseline evaluation
Measured: at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Occurence of cerebral infarction
Measured: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Cerebral blood flow change rate evaluated by single photon emission computed tomography
Frontal lobe
Measured: at 28 days post adrenomedullin administration
Safety: Serious adverse event
Measured: From the initiation of adrenomedullin administration to 28 days post
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2023
- Study start6 Jan 2022
- Primary completion23 Jan 2023
- Study completion12 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cerebral and Cardiovascular Center, Japan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Masafumi Ihara, National Cerebral and Cardiovascular Center, Japan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06072118
- Sponsor's protocol ID
- NCVC-AM-CAD
- Other IDs
- jRCT2051210117
- Acronym
- AMCAD
- Status last verified
- Oct 2023
- First submitted
- 2 Oct 2023
- Last updated
- 10 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Single-arm, Clinical Trial of Adrenomedullin for Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
- ClinicalTrials.gov ID
- NCT06072118
- Acronym / sponsor ID
- AMCAD / NCVC-AM-CAD
- Conditions
- Cadasil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Cerebral and Cardiovascular Center, JapanUniversity, hospital or other
- Study start
- 6 Jan 2022 (actual)
- Primary completion
- 23 Jan 2023 (actual)
- Study completion
- 12 Jun 2023 (actual)
- First posted
- 10 Oct 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.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary cerebral small vessel disease, with no proven disease-modifying treatments. Adrenomedullin, a vasoactive peptide, has angiogenic, vasodilation, anti-inflammatory, and anti-oxidative properties and could have triple sites of action on components of the neuro-glial-vascular unit consisting of vessels, microglia and oligodendrocytes or, more specifically, on the white matter oligovascular unit. The aim of the AMCAD trial is to assess the safety and efficacy of Adrenomedullin in CADASIL patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adrenomedullin group | Experimental | Drug: Adrenomedullin |
Who may qualify
- Ages
- 20 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients who have given written informed consent from the patient or the sponsor to participate in the clinical trial
- Patients aged between 20 and 90 at the time of obtaining consent
- Patients diagnosed as CADASIL after confirming NOTCH3 gene mutation by genetic testing
- Patients with Mini-mental state examination-J score of 10-27 or Trail maiking test score (age ajustment) of average + 1.5 SD (standard deviation) or higher
Key exclusion criteria (21 listed)
- Patients who cannot perform cognitive function tests (deafness, blindness, etc., MMSE-J less than 10 points Severe cognitive impairment, etc.)
- Patients received reatment with prohibited drugs or prohibited therapy within the past 12 weeks from the time of registration
- Patients who started to take concomitant restriction drugs or changed dosage of concomitant restriction drugs within the past 4 weeks from the time of registration
- Patients whose Mini-mental state examination-J with 4 or more points improvements between the time of registration and 4 weeks or more at the time of screening (If patients who take concomitant restriction drugs)
- Patients with active infections requiring antibiotic treatment at registration
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 |
|---|---|---|
| AdrenomedullinDosing at 15 ng/kg/min for 8 hours is continued for 14 days. | Drug | Adrenomedullin group |
Primary outcome
Cerebral blood flow change rate evaluated by arterial spin labeling
Time frame: at 28 days post adrenomedullin administration
Frontal lobe
10 secondary outcomes
Cerebral blood flow change rate evaluated by arterial spin labeling
Time frame: at 8 hours / 15 days / 90 days / 180 days post adrenomedullin administration
Cerebral blood flow change rate evaluated by arterial spin labeling
Time frame: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Mean diffusivity change rate of the white matter evaluated by MR diffusion tensor imaging
Time frame: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Fractional anisotropy change rate of the white matter evaluated by MR diffusion tensor imaging
Time frame: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Change in times of Trail making test-A/B from baseline evaluation
Time frame: at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Change in scores of Montreal cognitive assessment from baseline evaluation
Time frame: at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Change in scores of Wechsler Adult Intelligence Scale-Fourth edition from baseline evaluation
Time frame: at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Occurence of cerebral infarction
Time frame: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Cerebral blood flow change rate evaluated by single photon emission computed tomography
Time frame: at 28 days post adrenomedullin administration
Safety: Serious adverse event
Time frame: From the initiation of adrenomedullin administration to 28 days post
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 10 Oct 2023.
- Trial registrationLink provided by the sponsor.
Related trials for Cadasil
RecruitingObservational study
Registry for CADASIL
Cerebral Autosomal Dominant Ateriopathy With Subcortical Infarcts and Leukoencephalopathy
RecruitingObservational study
Natural History Study of CADASIL
Cardiovascular Disease, Arterial Stiffness
RecruitingObservational study
The Erlanger Stroke Registry (ESPro) is the Only Ongoing Prospective Population-based Stroke Registry in Germany, Started in 1994. ESPro Includes All Hospitalized and Non-hospitalized Patients With Stroke in the Community of Erlangen (120.000 Inhabitants), With a Long-life Follow-up.
Intracerebral Haemorrhage (ICH), Cerebral Infarction
Active, not recruitingObservational study
Florida Cerebrovascular Disease Biorepository and Genomics Center
Cerebrovascular Disease, Ischemic Stroke
RecruitingObservational study
Effect of the Mediterranean Diet in Patients Affected by CADASIL and Cerebral Amyloid Angiopathy.
Cerebral Amyloid Angiopathy, CAA - Cerebral Amyloid Angiopathy
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Adrenomedullin in people with Cadasil, run by National Cerebral and Cardiovascular Center, Japan at 1 site in Japan.
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 21 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 10 Oct 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 Japan. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Cerebral blood flow change rate evaluated by arterial spin labeling (time frame: at 28 days post adrenomedullin administration). 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 10 Oct 2023.