Using advanced MRI to explore metabolism and tissue structure in multiple sclerosis (MISSION MIMS)
| ISRCTN | ISRCTN10088443 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10088443 |
| IRAS number | 166097 |
| Secondary identifying numbers | IRAS 166097, CPMS 19436 |
- Submission date
- 16/11/2023
- Registration date
- 21/11/2023
- Last edited
- 12/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Multiple sclerosis (MS) is a brain degenerative condition caused by immune system changes. Magnetic Resonance Imaging (MRI) with contrast injection is the current standard for detection. In our study, we aim to use two new MRI techniques, 'Sodium MRI' and 'Carbon MRI,' to assess biological changes in MS-affected brains. Evidence suggests a buildup of 'lactate' in MS areas visible with 'Carbon MRI,' while 'Sodium MRI' images salt level changes. Another aspect of the study involves imaging glucose activity in the brain using Hyperpolarized Carbon and Deuterium MRI techniques. This substudy aims to compare the advantages of each method in measuring fast and slow glucose metabolism in MS patients.
We plan to compare brain images of both MS patients and healthy volunteers to understand normal versus abnormal brain patterns. The goal is to better understand MS-related brain changes, predicting treatment outcomes based on tissue lactate and glucose levels and blood vessel structure.
Who can participate?
Patients aged 18 years or older, with Multiple sclerosis. Healthy volunteers aged 18 years or older.
What does the study involve?
The MRI procedure involves a cylindrical machine with a plastic case over your head. 'Sodium MRI' is like a standard MRI, 'Carbon MRI' includes an injection of a natural sugar compound and 'Deuterium MRI' includes an administration of a sweet drink.
You might be offered an optional scan within 14 days to test the technique's repeatability.
Other procedures may include basic health checks, blood tests, and pregnancy tests, conducted with your well-being in mind.
Fasting for up to six hours before a scan may be required.
What are the possible benefits and risks of participating?
Taking part in this study may not directly help you, but it could help doctors find better ways to check for and keep track of brain tumours without using invasive methods. You will not be paid for taking part, we can cover your travel and parking costs.
MRI Scans: MRI scans are safe and do not involve X-rays or radioactivity. Some people might feel a bit closed-in (claustrophobic) or bothered by the noise, but you will be given earplugs and a squeeze-ball to help you feel more comfortable. The imaging software and hardware used are for research and not yet approved for routine diagnosis.
Incidental Findings: Although the scans are not part of your medical record, if we notice anything unusual, we will consult a specialist who may need to discuss it with you and your doctor.
Cannulation (inserting a small tube into a vein): This is a common procedure and is generally safe, but it might cause some discomfort or bruising at the insertion site. The cannula will be removed immediately after the scan.
Injection containing a substance called pyruvate: The injection is generally safe, with only mild and short-lasting side effects like flushing, feeling hot, dizziness or a metallic taste. Allergic reactions are highly unlikely, but we are prepared to manage any issues that may arise.
Sweet drink containing a substance called deuterated glucose: Glucose is a natural sugar that our body uses for energy, and deuterium is a safe form of hydrogen that is also found naturally in small amounts in our body. Scientists have previously studied water and glucose containing deuterium in people, and they did not find safety concerns. Any potential side effects will be managed by our team.
Where is the study run from?
Cambridge University Hospitals NHS Foundation Trust (UK).
When is the study starting and how long is it expected to run for?
July 2015 to December 2025
Who is funding the study?
MULTIPLE SCLEROSIS SOCIETY (UK)
Who is the main contact?
cuh.radiologyresearch@nhs.net
Contact information
Public, Scientific
Department of Radiology, Level 5, Box 218
Addenbrooke's Hospital, Hills Road
Cambridge
CB2 0QQ
United Kingdom
| Phone | +44(0)1223767926 |
|---|---|
| marta.wylot@nhs.net |
Principal Investigator
Department of Radiology, Level 5, Box 218
Addenbrooke's Hospital, Hills Road
Cambridge
CB2 0QQ
United Kingdom
 ORCID ID |
0000-0003-4784-5230 |
|---|---|
| Phone | +44 (0)1223 767062 |
| ferdia.gallagher@nhs.net |
Scientific
Box 218, Department of Radiology, Level 5
University of Cambridge School of Clinical Medicine
Cambridge Biomedical Campus
Cambridge
CB2 0QQ
United Kingdom
| maria.zamoramorales@nhs.net |
Study information
| Study design | Observational physiological imaging study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital, University/medical school/dental school |
| Study type | Diagnostic |
| Participant information sheet | 44606 MISSION-MIMS C13 Patient Information Sheet v6.0 06May2022.pdf |
| Scientific title | Molecular Imaging and Spectroscopy with Stable Isotopes in Oncology and Neurology: Imaging metabolism and tissue structure in Multiple Sclerosis with MRI (MISSION: MIMS) |
| Study acronym | MISSION: MIMS |
| Study objectives | The distribution of tissue sodium and the physiological metabolism of a glucose breakdown product, pyruvate can be assesed by hyperpolarised 13C-pyruvate MRI and sodium MRI. |
| Ethics approval(s) |
Approved 08/09/2015, NRES Committee East of England - Cambridge South (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, United Kingdom; +44 (0)115 883 9428; nrescommittee.eastofengland-cambridgesouth@nhs.net), ref: 15/EE/0255 |
| Health condition(s) or problem(s) studied | Multiple sclerosis |
| Intervention | Up to 15 patients with MS will be successfully imaged following injection with 13C pyruvate. Up to 40 healthy volunteers will be successfully imaged following injection with 13C pyruvate. An optional second imaging study up to 14 days later will be offered. Some of these volunteers will be asked to fast for 6 hours prior to the scan taking place. Up to 30 healthy volunteers will be recruited as part of the deuterium metabolic imaging (DMI) sub-study. Up to 15 patients with MS will be recruited as part of the deuterium metabolic imaging (DMI) sub-study. |
| Intervention type | Other |
| Primary outcome measure | Using MRI imaging: 1. 13C. Spatial maps of area under the curve (AUC) timecourse sums of signals from hyperpolarized pyruvate, lactate, and any other metabolites detected, and ratios between these metabolite AUCs. Also estimates of the kinetic rate constants of conversion between injected tracer pyruvate and the metabolites formed (lactate, other). The timecourse typically covers approximately 1 minute beginning approximately 16 seconds after the start of injection. 2. DMI. Spectral peak intensity ratios between deuterated water, glucose, glutamate (brain only), lactate and lipids. These will be either in spatial maps derived from 3D spectroscopic imaging, or in unlocalized spectra from the whole sensitive volume of the coil. |
| Secondary outcome measures | Sensitivity and spatial resolution of carbon-13 imaging of pyruvate and lactate in the human brain as measured by computing the signal-to-noise ratio in images of the area-under-the-curve of the timecourse signals of pyruvate, lactate and bicarbonate. |
| Overall study start date | 01/07/2015 |
| Completion date | 31/12/2025 |
Eligibility
| Participant type(s) | Healthy volunteer, Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 40 healthy volunteers, 30 patients with MS |
| Total final enrolment | 70 |
| Key inclusion criteria | MS patients (for C13 and DMI) 1. Be aged 18 years or older. 2. Have a confirmed diagnosis of MS. 3. Be aware of and understand their diagnosis. 4. Be able to provide written informed consent according to ICH/GCP, national and local regulations. 5. Be willing and able to comply with scheduled visits, laboratory tests, imaging and other study procedures. Healthy volunteers (C13 and DMI) 1. Be aged 18 years or older 2. Be able to provide written informed consent according to ICH/GCP, national and local regulations 3. Be willing and able to comply with scheduled visits, laboratory tests, imaging and other study procedures |
| Key exclusion criteria | MS patients (for C13 and DMI) 1. Have uncontrolled diabetes or glucose deranging conditions, or treatment that would cause such effects. 2. Have any medical condition that may increase the risk associated with study participation or in the judgement of the investigators make it unsuitable for the patient to enter the study. 3. Have a known allergy, adverse reaction or contraindication to any of the injected contrast agents used in this study including gadolinium contrast agents or pyruvate. 4. Be otherwise unsuitable for MRI e.g. having a permanent pacemaker, severe obesity or inability to lie still. 5. Be pregnant or breastfeeding Healthy volunteers (for C13 and DMI) 1. Have uncontrolled diabetes or glucose deranging conditions, or treatment that would cause such effects. The significance of this will be determined by the research team. 2. Have any medical condition that may increase the risk associated with study participation, or in the judgement of the investigators make it unsuitable for the patient to enter the study. 3. Have a known allergy, adverse reaction or contraindication to any of the injected contrast agents used in this study including gadolinium contrast agents or pyruvate. 4. Be otherwise unsuitable for MRI e.g. having a permanent pacemaker, severe obesity or inability to lie still. 5. Be pregnant or breastfeeding 6. Any previous or current neurological condition deemed to be significant by the research team. |
| Date of first enrolment | 30/03/2016 |
| Date of final enrolment | 30/11/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Hospital/treatment centre
Research and Development Department
Box 277
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
| Phone | +44 (0)1223 245151 |
|---|---|
| cuh.research@nhs.net | |
| Website | http://www.cuh.org.uk/ |
"ROR" |
https://ror.org/04v54gj93 |
Funders
Funder type
Not defined
Private sector organisation / Associations and societies (private and public)
- Alternative name(s)
- Multiple Sclerosis Society of Great Britain and Northern Ireland, The MS Society, MS Society UK, Multiple Sclerosis Society UK, MS Society
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/10/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Audiences for this research: 1. Scientific community 2. Funders, sponsors including NHS, ethics committees 3. Patients and the public Dissemination activities will include: 1. Abstracts, posters and talks for national and international scientific conferences 2. PPI events 3. Use of electronic media such as websites and specialised social networks such as Linkedin and ResearchGate 4. Publications including Full, Executive Summary and Plain English Summary reports of the research, peer review journals and local NHS/University of Cambridge newsletters. Whenever possible, open access to publications will be sought. This study may form part of a PhD thesis for a PhD student working in the research team. |
| IPD sharing plan | Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis. Access to trial IPD can be requested by qualified researchers engaging in independent scientific research and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact cuh.radiologyresearch@nhs.net. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | C13 Patient Information Sheet version 6.0 |
06/05/2022 | 21/11/2023 | No | Yes |
| Participant information sheet | C13 Volunteer Information Sheet version 6.0 |
06/05/2022 | 21/11/2023 | No | Yes |
| Participant information sheet | DMI Patient Information Sheet version 6.0 |
06/05/2022 | 21/11/2023 | No | Yes |
| Participant information sheet | DMI Volunteer Information Sheet version 6.0 |
06/05/2022 | 21/11/2023 | No | Yes |
| Protocol file | version 6.0 | 06/05/2022 | 21/11/2023 | No | No |
| Other publications | 15/04/2018 | 19/11/2024 | Yes | No | |
| Other publications | 01/02/2018 | 19/11/2024 | Yes | No | |
| Other publications | 01/06/2020 | 19/11/2024 | Yes | No | |
| Other publications | 18/01/2016 | 19/11/2024 | Yes | No | |
| Other publications | 04/09/2017 | 19/11/2024 | Yes | No | |
| Other publications | 22/10/2021 | 19/11/2024 | Yes | No | |
| Results article | 01/04/2019 | 19/11/2024 | Yes | No | |
| Results article | 15/08/2022 | 19/11/2024 | Yes | No |
Additional files
- 44606 MISSION-MIMS Protocol v6.0 06May2022.pdf
- 44606 MISSION-MIMS C13 Patient Information Sheet v6.0 06May2022.pdf
- C13 Patient Information Sheet
- 44606 MISSION-MIMS C13 Volunteer Information Sheet v6.0 06May2022.pdf
- C13 Volunteer Information Sheet
- 44606 MISSION-MIMS DMI Patient Information Sheet v6.0 06May2022.pdf
- DMI Patient Information Sheet
- 44606 MISSION-MIMS DMI Volunteer Information Sheet v6.0 06May2022.pdf
- DMI Volunteer Information Sheet
Editorial Notes
12/12/2024: The following changes were made:
1. The overall study end date was changed from 31/12/2024 to 31/12/2025.
2. The intention to publish date was changed from 01/10/2025 to 01/10/2026.
19/11/2024: Publication reference added.
22/07/2024: The contact emails were changed.
01/12/2023: Internal review.
21/11/2023: Trial's existence confirmed by NRES Committee East of England - Cambridge South.
