Multiple System AtrophyNCT05121012
Synaptic Loss in Multiple System Atrophy
An observational study of Multiple System Atrophy and Progressive Supranuclear Palsy (PSP), run by University of Exeter at 1 site in United Kingdom.
Trial summary
In this study the investigators would like to investigate the degree of damage of the synapses, an important part of the neurons vital for the communications between neurons, in Multiple System Atrophy (MSA), and pathology related to abnormal accumulation of a protein named tau, in Progressive Supranuclear Palsy (PSP). Read more about this study
- Who is it for?
- Ages 45 to 80 years
- Conditions the study is for
- Multiple System Atrophy, Progressive Supranuclear Palsy (PSP)
- What is being tested?
- Study procedures for MSA patients and Study procedures for PSP patients
- How many people
- 36 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2021to 31 Mar 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 45 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with a diagnosis of MSA; patients with a diagnosis of PSP
Who may be able to join
- MSA group:
- Male or female, aged 45-80 at the time of informed consent. Meet criteria for diagnosis of probable or possible MSA (Gilman et al., 2008) (Appendix 1).
- A female subject is eligible to participate if she is a) of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea or b) of childbearing potential but not pregnant (as determined by urinary pregnancy test on screening and on each study day), is not lactating and is willing to use one of the contraception methods listed below:
- Combined (estrogen and progesterone containing) hormonal contraception associated with initiation of ovulation( oral, intravaginal, or transdermal);
- Progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable);
- Intrauterine device;
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- Intrauterine hormone releasing system;
- Bilateral tubal occlusion;
- Vasectomized partner;
- Sexual abstinence.
- Male subject with a female partner of child-bearing potential must use one of the following contraceptive methods for 90 days after each dose of radiotracer:
- Condom plus partner use of a highly effective contraceptive (see point above) OR
- Abstinence Subjects must understand the nature of the study and be able to provide signed and dated written informed consent in accordance with local regulations before the conduct of any study-related procedures. They must be able and willing to participate in all scheduled evaluations, abide by all study restrictions, and complete all required tests and procedures.
- Must have anticipated survival of ≥3 years (in the opinion of the Investigator).
- Medical treatment of MSA and co-morbid medical conditions must be stable for at least 30 days prior to screening and between screening and baseline PET scan. Intermittently administered treatment may be considered stable if the dose and dosing frequency have been unchanged for the greater of 30 days or three dosing inbiomartervals (e.g. a treatment given once a month must be at a stable dose and dosing frequency for 3 months).
- For inclusion in optional CSF sampling, written informed consent must be provided, either by separate signed and dated written informed consent or by specific written acknowledgement on the main study informed consent form, according to local procedure. Failure to participate in optional CSF sampling will have no influence on the subject's ability to participate in the main study.
- In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have high probability of completing the study.
- PSP Group:
- Male or female, aged 45-80 at the time of informed consent. Meet criteria for diagnosis of suggestive, probable or possible PSP - with preference for PSP-RS, PSP-OM, PSP-PI, PSP with gait freezing, and PSP-SL and PSP-P subtypes (Höglinger et al., 2017 (Appendix 2).
- A female subject is eligible to participate if she is a) of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea or b) of childbearing potential but not pregnant (as determined by urinary pregnancy test on screening and on each study day), is not lactating and is willing to use one of the contraception methods listed below:
- Combined (estrogen and progesterone containing) hormonal contraception associated with initiation of ovulation( oral, intravaginal, or transdermal);
- Progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable);
- Intrauterine device;
- Intrauterine hormone releasing system;
- Bilateral tubal occlusion;
- Vasectomized partner; Sexual abstinence.
- Male subject with a female partner of child-bearing potential must use one of the following contraceptive methods for 90 days after each dose of radiotracer:
- Condom plus partner use of a highly effective contraceptive (see point above) OR Abstinence Subjects must understand the nature of the study and be able to provide signed and dated written informed consent in accordance with local regulations before the conduct of any study-related procedures. They must be able and willing to participate in all scheduled evaluations, abide by all study restrictions, and complete all required tests and procedures.
Who cannot join
- MSA group:
- History of other neurological disorders or intracranial co-morbidities, such as stroke, haemorrhage, space-occupying lesions.
- Presence of supranuclear gaze palsy. Presence of any clinically significant medical condition (including cardiovascular, respiratory, cerebrovascular, hematological, hepatic, renal, gastrointestinal, or other disease) that, based on the judgement of the investigator, is clinically unstable, is likely to deteriorate during the course of the study, could put the patient at risk because of participation in the study, could affect the subject's ability to complete the study, or could influence the study results.
- Severe-to-complete dependence on caregivers (score >3 on UMSARS Part IV, Global Disability), severe impairment of swallowing (score ≥3 on UMSARS Part I, Question 2), or frequent falls (score ≥3 on UMSARS Part I, Question 8) at Screening.
- Presence of any of the following MRI contraindications: pacemaker; cardiac defibrillator; spinal cord or vagus nerve stimulator; aneurysm clip; artificial heart valve; recent coronary or carotid stent; ear implant; CSF shunt; other implanted medical device (e.g. Swan-Ganz catheter, insulin pump); or metal fragments or foreign objects in the eyes, skin, or body. If the principal investigator considers the presence of any of the above not to be a contraindication to MRI in a given subject, the investigator may obtain approval from the MR operators based on a discussion of the case.Negative modified Allen test in both hands.
- History of claustrophobia or back pain that makes prolonged laying on the MRI or PET scanner intolerable.
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- Pregnancy, lactation, or, if female of childbearing potential, positive urine β-hCG at screening or prior to PET scan.
- Use of drugs acting on SV2A such as antiepileptics (e.g. levetiracetam or brivaracetam).
- History of brain surgery for parkinsonism or stem cell treatment. Clinically significant blood clotting or bleeding disorder, including clinically significant abnormal findings in laboratory assessments of coagulation or hematology.
- Current or recent history of alcohol or drug abuse / dependence (except nicotine dependence).
- History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma of the skin.
- Hemoglobin A1c (HbA1c) ≥ 6.5% at screening. Uncontrolled/poorly controlled diabetes mellitus.
- For subjects participating in optional CSF sampling:
- Any spinal malformation or other aspects (e.g. tattoos) / clinical findings (e.g. papilledema) that may complicate or contraindicate lumbar puncture, as judged by the investigator.
- Neoplasm or other space-occupying intracranial lesion on MRI. Any clinically important abnormality, as determined by the investigator, on physical examination or vital signs, ECG, or clinical laboratory test results other than abnormality due to a stable, well-controlled medical condition; or any abnormality that could be detrimental to the subject or could compromise the study.
- PSP group:
- History of other neurological disorders or intracranial co-morbidities, such as stroke, haemorrhage, space-occupying lesions.
- Inclusion in any clinical trial with investigational drugs targeting tau. Presence of any clinically significant medical condition (including cardiovascular, respiratory, cerebrovascular, hematological, hepatic, renal, gastrointestinal, or other disease) that, based on the judgement of the investigator, is clinically unstable, is likely to deteriorate during the course of the study, could put the patient at risk because of participation in the study, could affect the subject's ability to complete the study, or could influence the study results.
- Presence of any of the following MRI contraindications: pacemaker; cardiac defibrillator; spinal cord or vagus nerve stimulator; aneurysm clip; artificial heart valve; recent coronary or carotid stent; ear implant; CSF shunt; other implanted medical device (e.g. Swan-Ganz catheter, insulin pump); or metal fragments or foreign objects in the eyes, skin, or body. If the principal investigator considers the presence of any of the above not to be a contraindication to MRI in a given subject, the investigator may obtain approval from the MR operators based on a discussion of the case.
- Abnormal modified Allen test in both hands. History of claustrophobia or back pain that makes prolonged laying on the MRI or PET scanner intolerable.
- Pregnancy, lactation, or, if female of childbearing potential, positive urine β-hCG at screening or prior to PET scan.
- History of brain surgery for parkinsonism or stem cell treatment. Clinically significant blood clotting or bleeding disorder, including clinically significant abnormal findings in laboratory assessments of coagulation or hematology.
- Current or recent history of alcohol or drug abuse / dependence (except nicotine dependence).
- History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma of the skin.
- For subjects participating in optional CSF sampling:
- Any spinal malformation or other aspects (e.g. tattoos) / clinical findings (e.g. papilledema) that may complicate or contraindicate lumbar puncture, as judged by the investigator.
- Neoplasm or other space-occupying intracranial lesion on MRI. Any clinically important abnormality, as determined by the investigator, on physical examination or vital signs, ECG, or clinical laboratory test results other than abnormality due to a stable, well-controlled medical condition; or any abnormality that could be detrimental to the subject or could compromise the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Heather Wilson, MSc Ph.D contact
United Kingdom1 site, 1 recruiting
- Recruiting
University of Exeter
Exeter, SE16 7RJ
Edoardo R de Natale, MD MSc PhD, 07503741242, e.de-natale@exeter.ac.uk
About this study
Official title: Molecular Imaging of Synaptic Loss in Multiple System Atrophy (MSA)
In this study the investigators would like to investigate the degree of damage of the synapses, an important part of the neurons vital for the communications between neurons, in Multiple System Atrophy (MSA), and pathology related to abnormal accumulation of a protein named tau, in Progressive Supranuclear Palsy (PSP).
Read the detailed description
Multiple System Atrophy (MSA) is a chronic and progressive neurological disease, for which unfortunately there is no cure yet. It is known from pathological studies that the synapses (the terminal parts of the neurons) are affected in this disease, but the investigators don't know how, and how much this happens. An imaging tool called Positron Emission Tomography (PET) can study the integrity of the synapses by the use of a dedicated tracer, called [11C]UCB-J. In this study the investigators would like to study how, and how early, the synapse deteriorate in patients with MSA.
For this study, patients with the MSA will be enrolled. Participants will be asked to undergo a clinical visit with questionnaires and scales for motor and cognitive symptoms. Then, participants will come for a [11C]UCB-J PET scan, a [18F]FDG PET scan, to check the metabolism of the brain, and a MRI scan, to help the analysis of the PET. The participants will also be asked to perform a Lumbar puncture for a cerebrospinal fluid draw. This procedure will be optional.
A subgroup of up to 10 patients with MSA who took part to the main study will also undergo an imaging substudy, with a PET scan (only at a single timepoint) with the tracer [18F]APN107. [18F]APN107 is a novel tracer measuring a protein in the brain named tau. Tau abnormally accumulates in patients with a disease named Progressive Supranuclear Palsy (PSP) but not in MSA. It is sometimes very challenging to distinguish MSA and PSP on the basis of the clinical observation. We hope that a PET scan with [18F]APN107 could help distinguish these disorders more. This subgroup of patients with MSA will be compared with a group of up to 16 patients with PSP (the clinical forms named PSP-RS and PSP-P) who will undergo the following activities:
At baseline, a clinical visit with administration of pen-and-paper tests and scales,, a venous blood collection, an MRI scan and one [18F]APN107 PET scan; After approximately one year from baseline (follow-up), the repetition of the same activities as at baseline.
The results will help in understanding better the mechanisms underlying thiese two conditions and open new avenues for its treatment.
- Being tested
- Study procedures for MSA patients, Study procedures for PSP patients
- Keywords
- Neurodegeneration, Positron Emission Tomography, Multiple System Atrophy, Biomarkers, Progressive Supranuclear Palsy
- Medical subject headings
- Multiple System Atrophy, Supranuclear Palsy, Progressive, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Study procedures for MSA patientsOther
The group of MSA patients will undergo a collection of demographic data, a neurological examination with administration of clinical scales relevant for MSA, and a collection of venous blood sample for routine and biomarker analyses.
Participants will undergo one PET scan with the tracer [11C]UCB-J, and one PET scan with the tracer [18F]FDG. All participants will also undergo one MRI scan.
Participants will also undergo one lumbar puncture (optional).
All procedures will be performed at baseline and after one-year follow-up.
A subgroup of patients with MSA will also undergo, at one time point only, one PET scan with the tracer [18F]APN107.
Study procedures for PSP patientsOther
The group of PSP patients will undergo a collection of demographic data, a neurological examination with administration of clinical scales relevant for PSP, and a collection of venous blood sample for routine and biomarker analyses. Participants will undergo one PET scan with the tracer [18F]APN107 and one MRI scan. All procedures will be performed at baseline and after one-year follow-up.
| Study group | Role | What they receive |
|---|---|---|
| Patients with MSA | Patients with a diagnosis of MSA and either a clinical form MSA-C or MSA-P Receives: Other: Study procedures for MSA patients | |
| Patients with Progressive Supranuclear Palsy | Patients with a diagnosis of PSP, either the clinical forms PSP-RS or PSP-P Receives: Other: Study procedures for PSP patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
To measure the magnitude of longitudinal within-group change in [11C]UCB-J volume of distribution in MSA
[11C]UCB-J is a marker of synaptic damage in MSA
Measured: Baseline to 12 Months
Secondary outcomes (27)
Progression of brain glucose metabolism in MSA
Brain glucose metabolism is assessed with serial [18F]FDG PET scans at baseline and after 12-month follow-up.
Measured: Baseline to 12 Months
To investigate differences in MRI structural, microstructural, molecular, and functional parameters in MSA patients.
Magnetic Resonance Imaging change in Magnetization Prepared Rapid Acquisition Gradient Echo [MPRAGE]
Measured: Baseline to 12 Months
To investigate differences in structural MRI parameters in MSA patients.
Magnetic Resonance Imaging change in Magnetization Prepared Rapid Acquisition Gradient Echo [MPRAGE]
Measured: Baseline to 12 Months
To investigate differences in iron-sensitive MRI in MSA patients.
Magnetic Resonance Imaging change in Susceptibility Weighted Imaging [SWI]
Measured: Baseline to 12 Months
To investigate differences in quantitative iron in MSA patients.
Magnetic Resonance Imaging change in Quantitative Susceptibility Mapping [QSM]
Measured: Baseline to 12 Months
To investigate differences in microstructural MRI parameters in MSA patients.
Magnetic Resonance Imaging change in Diffusion Tensor Imaging [DTI]
Measured: Baseline to 12 Months
To investigate differences in neuromelanin-MRI in MSA patients.
Magnetic Resonance Imaging change in Neuromelanin-MRI
Measured: Baseline to 12 Months
To investigate differences in perfusion MRI parameters in MSA patients.
Magnetic Resonance Imaging change in Arterial Spin Labelling [ASL]
Measured: Baseline to 12 Months
To investigate differences in functional MRI parameters in MSA patients.
Magnetic Resonance Imaging change in resting state functional MRI [rs-fMRI]
Measured: Baseline to 12 Months
To investigate differences in markers of neurite density on MRI in MSA patients.
Magnetic Resonance Imaging change in Neurite Orientation Dispersion and Density Imaging [NODDI]
Measured: Baseline to 12 Months
To investigate correlations between imaging and grading of MSA in MSA patients.
Correlations between imaging measures and the grading scale UMSARS
Measured: Baseline to 12 Months
To investigate correlations between imaging and staging of MSA in MSA patients.
Correlations between imaging measures and the staging scale Hoehn and Yahr
Measured: Baseline to 12 Months
To investigate correlations between synaptic density, regional brain glucose metabolism, and clinical measures in MSA patients.
Correlations between imaging measures and the screening cognitive measure MoCA
Measured: Baseline to 12 Months
To investigate correlations between imaging measures and functional scales in MSA patients.
Correlations between imaging measures and the ability scale Schwab \& England
Measured: Baseline to 12 Months
To investigate correlations between imaging measures and quality of life in MSA patients.
Correlations between imaging measures and the quality of life scale MSA QoL
Measured: Baseline to 12 Months
To investigate correlations between imaging measures and symptoms of autonomic dysfunction in MSA patients.
Correlations between imaging measures and the autonomic symptoms scale COMPASS-31
Measured: Baseline to 12 Months
To investigate correlations between imaging measures and symptoms of postural instability and tendency to fall in MSA patients.
Correlations between imaging measures and the balance scale ABC-16
Measured: Baseline to 12 Months
To investigate correlations between imaging measures and symptoms of depression in MSA patients.
Correlations between imaging measures and the depression scale BDI-II
Measured: Baseline to 12 Months
To investigate correlations between imaging measures and symptoms suggestive of depression in MSA patients.
Correlations between imaging measures and the depression scale HDRS
Measured: Baseline to 12 Months
To investigate correlations between imaging measures and REM sleep behaviour disorder in MSA patients.
Correlations between imaging measures and the sleep scale RBD-SQ
Measured: Baseline to 12 Months
To investigate correlations between imaging measures and presence of behavioural symptoms in MSA patients.
Correlations between imaging measures and the behavioural scale NPI
Measured: Baseline to 12 Months
To investigate correlations between imaging measures and cognitive decline in MSA patients.
Correlations between imaging measures and the cognitive battery CANTAB
Measured: Baseline to 12 Months
To investigate correlations between imaging measures and fluid biomarkers of inflammation in MSA patients.
Correlations between imaging measures and blood biomarkers related to neuroinflammation
Measured: Baseline to 12 Months
To investigate correlations between imaging measures and CSF biomarkers in MSA patients.
Correlations between imaging measures and CSF biomarkers related to neuroinflammation and misfolded proteins deposition
Measured: Baseline to 12 Months
Change in [18F]APN107 brain uptake in patients with PSP
Quantification of the changes over time of [18F]APN107 brain uptake, reflective of tau deposition, in patients with PSP
Measured: Baseline to 12 months
Correlation between longitudinal changes in [18F]APN107 and structural changes on MRI
Magnetic Resonance Imaging change in Magnetization Prepared Rapid Acquisition Gradient Echo [MPRAGE]
Measured: Baseline to 12 months
To investigate differences in tau pathology across MSA and PSP patients
differences in the brain uptake of [18F]APN107 between MSA and PSP patients
Measured: Baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2021
- Study start1 Sep 2021
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple System AtrophyStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Exeter
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marios Politis, MD MSc PhD, Study chair, University of Exeter
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05121012
- Sponsor's protocol ID
- 1920/15
- Status last verified
- Feb 2026
- First submitted
- 29 Sep 2021
- Last updated
- 10 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Imaging of Synaptic Loss in Multiple System Atrophy (MSA)
- ClinicalTrials.gov ID
- NCT05121012
- Acronym / sponsor ID
- 1920/15
- Keywords
- Neurodegeneration, Positron Emission Tomography, Multiple System Atrophy, Biomarkers, Progressive Supranuclear Palsy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- University of ExeterUniversity, hospital or other
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 16 Nov 2021 (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 this study the investigators would like to investigate the degree of damage of the synapses, an important part of the neurons vital for the communications between neurons, in Multiple System Atrophy (MSA), and pathology related to abnormal accumulation of a protein named tau, in Progressive Supranuclear Palsy (PSP).
Detailed description
Multiple System Atrophy (MSA) is a chronic and progressive neurological disease, for which unfortunately there is no cure yet. It is known from pathological studies that the synapses (the terminal parts of the neurons) are affected in this disease, but the investigators don't know how, and how much this happens. An imaging tool called Positron Emission Tomography (PET) can study the integrity of the synapses by the use of a dedicated tracer, called [11C]UCB-J. In this study the investigators would like to study how, and how early, the synapse deteriorate in patients with MSA.
For this study, patients with the MSA will be enrolled. Participants will be asked to undergo a clinical visit with questionnaires and scales for motor and cognitive symptoms. Then, participants will come for a [11C]UCB-J PET scan, a [18F]FDG PET scan, to check the metabolism of the brain, and a MRI scan, to help the analysis of the PET. The participants will also be asked to perform a Lumbar puncture for a cerebrospinal fluid draw. This procedure will be optional.
A subgroup of up to 10 patients with MSA who took part to the main study will also undergo an imaging substudy, with a PET scan (only at a single timepoint) with the tracer [18F]APN107. [18F]APN107 is a novel tracer measuring a protein in the brain named tau. Tau abnormally accumulates in patients with a disease named Progressive Supranuclear Palsy (PSP) but not in MSA. It is sometimes very challenging to distinguish MSA and PSP on the basis of the clinical observation. We hope that a PET scan with [18F]APN107 could help distinguish these disorders more. This subgroup of patients with MSA will be compared with a group of up to 16 patients with PSP (the clinical forms named PSP-RS and PSP-P) who will undergo the following activities:
At baseline, a clinical visit with administration of pen-and-paper tests and scales,, a venous blood collection, an MRI scan and one [18F]APN107 PET scan; After approximately one year from baseline (follow-up), the repetition of the same activities as at baseline.
The results will help in understanding better the mechanisms underlying thiese two conditions and open new avenues for its treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with MSA | – | Other: Study procedures for MSA patientsPatients with a diagnosis of MSA and either a clinical form MSA-C or MSA-P |
| Patients with Progressive Supranuclear Palsy | – | Other: Study procedures for PSP patientsPatients with a diagnosis of PSP, either the clinical forms PSP-RS or PSP-P |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a diagnosis of MSA; patients with a diagnosis of PSP
Key inclusion criteria (28 listed)
- Male or female, aged 45-80 at the time of informed consent. Meet criteria for diagnosis of probable or possible MSA (Gilman et al., 2008) (Appendix 1).
- A female subject is eligible to participate if she is a) of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea or b) of childbearing potential but not pregnant (as determined by urinary pregnancy test on screening and on each study day), is not lactating and is willing to use one of the contraception methods listed below:
- Combined (estrogen and progesterone containing) hormonal contraception associated with initiation of ovulation( oral, intravaginal, or transdermal);
- Progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable);
- Intrauterine device;
Key exclusion criteria (27 listed)
- History of other neurological disorders or intracranial co-morbidities, such as stroke, haemorrhage, space-occupying lesions.
- Presence of supranuclear gaze palsy. Presence of any clinically significant medical condition (including cardiovascular, respiratory, cerebrovascular, hematological, hepatic, renal, gastrointestinal, or other disease) that, based on the judgement of the investigator, is clinically unstable, is likely to deteriorate during the course of the study, could put the patient at risk because of participation in the study, could affect the subject's ability to complete the study, or could influence the study results.
- Severe-to-complete dependence on caregivers (score >3 on UMSARS Part IV, Global Disability), severe impairment of swallowing (score ≥3 on UMSARS Part I, Question 2), or frequent falls (score ≥3 on UMSARS Part I, Question 8) at Screening.
- Presence of any of the following MRI contraindications: pacemaker; cardiac defibrillator; spinal cord or vagus nerve stimulator; aneurysm clip; artificial heart valve; recent coronary or carotid stent; ear implant; CSF shunt; other implanted medical device (e.g. Swan-Ganz catheter, insulin pump); or metal fragments or foreign objects in the eyes, skin, or body. If the principal investigator considers the presence of any of the above not to be a contraindication to MRI in a given subject, the investigator may obtain approval from the MR operators based on a discussion of the case.Negative modified Allen test in both hands.
- History of claustrophobia or back pain that makes prolonged laying on the MRI or PET scanner intolerable.
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 |
|---|---|---|
| Study procedures for MSA patientsThe group of MSA patients will undergo a collection of demographic data, a neurological examination with administration of clinical scales relevant for MSA, and a collection of venous blood sample for routine and biomarker analyses. Participants will undergo one PET scan with the tracer [11C]UCB-J, and one PET scan with the tracer [18F]FDG. All participants will also undergo one MRI scan. Participants will also undergo one lumbar puncture (optional). All procedures will be performed at baseline and after one-year follow-up. A subgroup of patients with MSA will also undergo, at one time point only, one PET scan with the tracer [18F]APN107. | Other | Patients with MSA |
| Study procedures for PSP patientsThe group of PSP patients will undergo a collection of demographic data, a neurological examination with administration of clinical scales relevant for PSP, and a collection of venous blood sample for routine and biomarker analyses. Participants will undergo one PET scan with the tracer [18F]APN107 and one MRI scan. All procedures will be performed at baseline and after one-year follow-up. | Other | Patients with Progressive Supranuclear Palsy |
Primary outcome
To measure the magnitude of longitudinal within-group change in [11C]UCB-J volume of distribution in MSA
Time frame: Baseline to 12 Months
[11C]UCB-J is a marker of synaptic damage in MSA
27 secondary outcomes
Progression of brain glucose metabolism in MSA
Time frame: Baseline to 12 Months
To investigate differences in MRI structural, microstructural, molecular, and functional parameters in MSA patients.
Time frame: Baseline to 12 Months
To investigate differences in structural MRI parameters in MSA patients.
Time frame: Baseline to 12 Months
To investigate differences in iron-sensitive MRI in MSA patients.
Time frame: Baseline to 12 Months
To investigate differences in quantitative iron in MSA patients.
Time frame: Baseline to 12 Months
To investigate differences in microstructural MRI parameters in MSA patients.
Time frame: Baseline to 12 Months
To investigate differences in neuromelanin-MRI in MSA patients.
Time frame: Baseline to 12 Months
To investigate differences in perfusion MRI parameters in MSA patients.
Time frame: Baseline to 12 Months
To investigate differences in functional MRI parameters in MSA patients.
Time frame: Baseline to 12 Months
To investigate differences in markers of neurite density on MRI in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging and grading of MSA in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging and staging of MSA in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between synaptic density, regional brain glucose metabolism, and clinical measures in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging measures and functional scales in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging measures and quality of life in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging measures and symptoms of autonomic dysfunction in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging measures and symptoms of postural instability and tendency to fall in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging measures and symptoms of depression in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging measures and symptoms suggestive of depression in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging measures and REM sleep behaviour disorder in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging measures and presence of behavioural symptoms in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging measures and cognitive decline in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging measures and fluid biomarkers of inflammation in MSA patients.
Time frame: Baseline to 12 Months
To investigate correlations between imaging measures and CSF biomarkers in MSA patients.
Time frame: Baseline to 12 Months
Change in [18F]APN107 brain uptake in patients with PSP
Time frame: Baseline to 12 months
Correlation between longitudinal changes in [18F]APN107 and structural changes on MRI
Time frame: Baseline to 12 months
To investigate differences in tau pathology across MSA and PSP patients
Time frame: Baseline to 12 months
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 10 Feb 2026.
- 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.
Heather Wilson, MSc Ph.D contact
Marios Politis, MD MSc PhD study chair
University of Exeter
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 Multiple System Atrophy and Progressive Supranuclear Palsy (PSP), run by University of Exeter at 1 site in United Kingdom.
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 28 inclusion and 27 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: looking for participants now, as of the sponsor's last update on 10 Feb 2026. 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 United Kingdom. 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 Edoardo R. de Natale, MD MSc Ph.D (07503741242, e.de-natale@exeter.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To measure the magnitude of longitudinal within-group change in [11C]UCB-J volume of distribution in MSA (time frame: Baseline to 12 Months). 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 Feb 2026.