Synaptic Loss in Multiple System Atrophy

NCT05121012 | Recruiting

• 1 other identifier: 1920/15
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Multiple System Atrophy; Progressive Supranuclear Palsy (PSP)

Keywords

Neurodegeneration; Positron Emission Tomography; Multiple System Atrophy; Biomarkers; Progressive Supranuclear Palsy

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline to 12 Months

Secondary Outcomes (27)

• Progression of brain glucose metabolism in MSA

  Baseline to 12 Months

• To investigate differences in MRI structural, microstructural, molecular, and functional parameters in MSA patients.

  Baseline to 12 Months

• To investigate differences in structural MRI parameters in MSA patients.

  Baseline to 12 Months

• To investigate differences in iron-sensitive MRI in MSA patients.

  Baseline to 12 Months

• To investigate differences in quantitative iron in MSA patients.

  Baseline to 12 Months

Study Arms (2)

Patients with MSA

Patients with a diagnosis of MSA and either a clinical form MSA-C or MSA-P

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

Other: Study procedures for PSP patients

Interventions

Study procedures for MSA patients OTHER

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.

Patients with MSA

Study procedures for PSP patients OTHER

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.

Patients with Progressive Supranuclear Palsy

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of MSA; patients with a diagnosis of PSP

You may qualify if:

• 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;
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Exeter: lead

Study Sites (1)

University of Exeter

Exeter, SE16 7RJ, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Venous blood will be collected for analysis of inflammatory biomarkers (including CRP, IL-6, IL-1b, TNF, ferritin, ESR, NfL) and for storage in biobanks for future ethically approved studies. Cerebrospinal fluid (CSF) will be collected for analysis of cell count and for biomarkers (for MSA only).

MeSH Terms

Conditions

Multiple System Atrophy; Supranuclear Palsy, Progressive; Nerve Degeneration

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Study Officials

• Marios Politis, MD MSc PhD

  University of Exeter

  STUDY CHAIR

Central Study Contacts

Edoardo R. de Natale, MD MSc Ph.D

CONTACT

07503741242; e.de-natale@exeter.ac.uk

Heather Wilson, MSc Ph.D

CONTACT

h.wilson4@exeter.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: November 16, 2021
• Study Start: September 1, 2021
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)