Asmd, Visceral TypeMONACONCT05904366
Magnetic Resonance Spectroscopy in Acid Sphingomyelinase Deficiency
A study testing MR Spectroscopy (MRS) and MR Elastography (MRE) in people with Asmd, Visceral Type, run by Eline C. B. Eskes at 1 site in Netherlands.
Trial summary
The goal of this study is to assess the ability of MRI techniques to detect early stages of lipid accumulation in the liver of ASMD patients with the chronic visceral subtype compared to healthy subjects. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Asmd, Visceral Type
- What is being tested?
- MR Spectroscopy (MRS) and MR Elastography (MRE)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteNetherlands
- Study dates
- 5 May 2023to 1 Sep 2024
- Phase
- Interventional
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients:
- The patient has biochemically proven ASMD (preferably genetically confirmed)
- The patient is willing and able to provide written informed consent prior to the study-related procedure.
- The patient is ≥ 18 years of age
- Healthy controls:
- The individual is willing and able to provide written informed consent prior to the study-related procedure
- The individual is ≥ 18 years of age
- General good health as determined by medical history
Who cannot join
- Patients and healthy controls:
- Inability to adhere to the study protocol
- Inability to undergo an MRI procedure
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC
Amsterdam, North Holland, 1105 AZ
Eline CB Eskes, MD, 0205669111, e.c.eskes@amsterdamumc.nl
About this study
The goal of this study is to assess the ability of MRI techniques to detect early stages of lipid accumulation in the liver of ASMD patients with the chronic visceral subtype compared to healthy subjects.
Participants will undergo an MRI with MR Spectroscopy (MRS) to measure lipid accumulation (steatosis) and MR Elastography (MRE) to measure liver stiffness (fibrosis).
Read the detailed description
Rationale: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder caused by a deficiency of sphingomyelinase resulting in accumulation of the sphingolipid sphingomyelin (SM) in the liver, spleen and lungs. Accumulation of SM in the liver leads to liver fibrosis in a subset of ASMD patients. Enzyme replacement therapy (ERT, olipudase alfa, Sanofi Genzyme) is currently investigated in a phase 2/3 trial and recently received market authorization by the EMA and FDA. As ASMD is a slowly progressive disease, detection of early stages of SM storage in the liver might aid in identifying patients at risk for major complications who would benefit from therapy. Two magnetic resonance (MR) based techniques might be of interest: MR Spectroscopy (MRS) to measure lipid accumulation (steatosis) and MR Elastography (MRE) to measure liver stiffness (fibrosis).
Objective: To assess the ability of MRI techniques to detect early stages of lipid accumulation in the liver of ASMD patients with the chronic visceral subtype compared to healthy subjects.
Study design: Cross-sectional pilot study in which MRS and MRE measurements of ASMD patients will be compared to measurements in healthy subjects. All ASMD patients who participate will undergo an MRI during their yearly assessments. Patients eligible for therapy will also undergo an MRI after one year of treatment.
Study population: All adult patients with ASMD visiting the outpatient clinic for metabolic disorders of the Amsterdam UMC will be invited to participate. Participating ASMD patients will be matched to healthy controls based on age, sex and BMI in a ratio of 1:1.
Main study endpoint: Fat fraction in volume percentage (%) of liver tissue of ASMD patients measured with MRS compared to values of healthy subjects.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The MRI procedure yields no risk: at most patients might feel uncomfortable lying in the tight space. Patients and healthy subjects will not directly benefit from participation in the study. The results of the study may improve clinical care in the future.
- Conditions
- Asmd, Visceral Type
- Being tested
- MR Spectroscopy (MRS), MR Elastography (MRE)
- Medical subject headings
- Niemann-Pick Disease, Type B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MR Spectroscopy (MRS)Diagnostic test
MR Spectroscopy (MRS)
MR Elastography (MRE)Diagnostic test
MR Elastography (MRE) with a device that induces shear waves in the body. This device is placed upon the abdomen of the subject and is hold in place by straps. The device will produce low-frequency vibrations (e.g. 30-60 Hz) which are not painful to the participant. A declaration of conformity and a safety document are provided in the study dossier.
| Study group | Role | What they receive |
|---|---|---|
| Patients | Other | Participants will undergo an MRI with MR Spectroscopy (MRS) and MR Elastography (MRE) measurements Receives: Diagnostic Test: MR Spectroscopy (MRS); Diagnostic Test: MR Elastography (MRE) |
| Healthy controls | Other | Participants will undergo an MRI with MR Spectroscopy (MRS) and MR Elastography (MRE) measurements Receives: Diagnostic Test: MR Spectroscopy (MRS); Diagnostic Test: MR Elastography (MRE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fat fraction in volume percentage measured with MRS-PDFF
Fat fraction in volume percentage measured with MRS-PDFF of ASMD patients compared to age-, sex, and BMI-matched healthy subjects.
Measured: 1 year
Secondary outcomes (3)
Liver stiffness in kPa measured with MRE
Liver stiffness in kPa measured with MRE of ASMD patients compared to age-, sex, and BMI-matched healthy subjects.
Measured: 1 year
Correlations between fat fraction and/or liver stiffness and liver parameters
Correlations between fat fraction and/or liver stiffness and liver parameters (i.e. liver stiffness measured with fibroscan, liver volume and plasma ALT and AST levels)
Measured: 1 year
Correlations between fat fraction and/or liver stiffness and general disease parameters
Correlations between fat fraction and/or liver stiffness and general disease parameters (i.e. spleen volume, CO diffusion capacity, plasma LSM, LSM-509 and chitotriosidase levels)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2023
- Study start5 May 2023
- Primary completion1 Apr 2024 (estimated)
- Study completion1 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asmd, Visceral TypeStudies 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Cross-sectional pilot study in which MRS and MRE measurements of ASMD patients will be compared to measurements in healthy subjects.
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eline C. B. Eskes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Eline C. B. Eskes, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Carla EM Hollak, prof dr, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)xx xx xx, xx, Study director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05904366
- Sponsor's protocol ID
- 2022.0444
- Acronym
- MONACO
- Status last verified
- Jun 2023
- First submitted
- 6 Jun 2023
- Last updated
- 15 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Research data will be submitted as articles to peer-reviewed journals. Also, an abstract of our research data reporting our findings will be submitted for presentations on scientific, public and/or patient organization meetings for (oral) presentation(s).
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Magnetic Resonance Spectroscopy in Acid Sphingomyelinase Deficiency
- ClinicalTrials.gov ID
- NCT05904366
- Acronym / sponsor ID
- MONACO / 2022.0444
- Conditions
- Asmd, Visceral Type
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Eline C. B. EskesUniversity, hospital or other
- Study start
- 5 May 2023 (actual)
- Primary completion
- 1 Apr 2024 (estimated)
- Study completion
- 1 Sep 2024 (estimated)
- First posted
- 15 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.
The goal of this study is to assess the ability of MRI techniques to detect early stages of lipid accumulation in the liver of ASMD patients with the chronic visceral subtype compared to healthy subjects.
Participants will undergo an MRI with MR Spectroscopy (MRS) to measure lipid accumulation (steatosis) and MR Elastography (MRE) to measure liver stiffness (fibrosis).
Detailed description
Rationale: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder caused by a deficiency of sphingomyelinase resulting in accumulation of the sphingolipid sphingomyelin (SM) in the liver, spleen and lungs. Accumulation of SM in the liver leads to liver fibrosis in a subset of ASMD patients. Enzyme replacement therapy (ERT, olipudase alfa, Sanofi Genzyme) is currently investigated in a phase 2/3 trial and recently received market authorization by the EMA and FDA. As ASMD is a slowly progressive disease, detection of early stages of SM storage in the liver might aid in identifying patients at risk for major complications who would benefit from therapy. Two magnetic resonance (MR) based techniques might be of interest: MR Spectroscopy (MRS) to measure lipid accumulation (steatosis) and MR Elastography (MRE) to measure liver stiffness (fibrosis).
Objective: To assess the ability of MRI techniques to detect early stages of lipid accumulation in the liver of ASMD patients with the chronic visceral subtype compared to healthy subjects.
Study design: Cross-sectional pilot study in which MRS and MRE measurements of ASMD patients will be compared to measurements in healthy subjects. All ASMD patients who participate will undergo an MRI during their yearly assessments. Patients eligible for therapy will also undergo an MRI after one year of treatment.
Study population: All adult patients with ASMD visiting the outpatient clinic for metabolic disorders of the Amsterdam UMC will be invited to participate. Participating ASMD patients will be matched to healthy controls based on age, sex and BMI in a ratio of 1:1.
Main study endpoint: Fat fraction in volume percentage (%) of liver tissue of ASMD patients measured with MRS compared to values of healthy subjects.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The MRI procedure yields no risk: at most patients might feel uncomfortable lying in the tight space. Patients and healthy subjects will not directly benefit from participation in the study. The results of the study may improve clinical care in the future.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Cross-sectional pilot study in which MRS and MRE measurements of ASMD patients will be compared to measurements in healthy subjects.
| Arm | Type | Receives |
|---|---|---|
| Patients | Other | Diagnostic Test: MR Spectroscopy (MRS), Diagnostic Test: MR Elastography (MRE)Participants will undergo an MRI with MR Spectroscopy (MRS) and MR Elastography (MRE) measurements |
| Healthy controls | Other | Diagnostic Test: MR Spectroscopy (MRS), Diagnostic Test: MR Elastography (MRE)Participants will undergo an MRI with MR Spectroscopy (MRS) and MR Elastography (MRE) measurements |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The patient has biochemically proven ASMD (preferably genetically confirmed)
- The patient is willing and able to provide written informed consent prior to the study-related procedure.
- The patient is ≥ 18 years of age
- The individual is willing and able to provide written informed consent prior to the study-related procedure
- The individual is ≥ 18 years of age
Key exclusion criteria (3 listed)
- Inability to adhere to the study protocol
- Inability to undergo an MRI procedure
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 |
|---|---|---|
| MR Spectroscopy (MRS)MR Spectroscopy (MRS) | Diagnostic test | Healthy controls, Patients |
| MR Elastography (MRE)MR Elastography (MRE) with a device that induces shear waves in the body. This device is placed upon the abdomen of the subject and is hold in place by straps. The device will produce low-frequency vibrations (e.g. 30-60 Hz) which are not painful to the participant. A declaration of conformity and a safety document are provided in the study dossier. | Diagnostic test | Healthy controls, Patients |
Primary outcome
Fat fraction in volume percentage measured with MRS-PDFF
Time frame: 1 year
Fat fraction in volume percentage measured with MRS-PDFF of ASMD patients compared to age-, sex, and BMI-matched healthy subjects.
3 secondary outcomes
Liver stiffness in kPa measured with MRE
Time frame: 1 year
Correlations between fat fraction and/or liver stiffness and liver parameters
Time frame: 1 year
Correlations between fat fraction and/or liver stiffness and general disease parameters
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2023.
- Individual participant dataSharing planned: Undecided. Research data will be submitted as articles to peer-reviewed journals. Also, an abstract of our research data reporting our findings will be submitted for presentations on scientific, public and/or patient organization meetings for (oral) presentation(s).
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.
Carla EM Hollak, prof dr principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
xx xx xx, xx study director
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MR Spectroscopy (MRS) and MR Elastography (MRE) in people with Asmd, Visceral Type, run by Eline C. B. Eskes at 1 site in Netherlands.
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 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 15 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 Netherlands. 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 Eline CB Eskes, MD (0205669111, e.c.eskes@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fat fraction in volume percentage measured with MRS-PDFF (time frame: 1 year). 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 15 Jun 2023.