Parkinson DiseaseNCT05741151
Superior Cervical Ganglion in Parkinson's Disease
A study testing PET-Neck Parkinsonian patients in people with Parkinson Disease, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
In several neurodegenerative diseases, such as Parkinson's disease, the progressive loss of neurons of monoaminergic systems leads to the development of characteristic clinical manifestations. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- PET-Neck Parkinsonian patients
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2023to 31 Dec 2026
- Phase
- Interventional
- 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 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients affected with Parkinson Disease according to the criteria defined by the Movements Disorder Society
Who cannot join
- Unambiguous cerebellar abnormalities, such as cerebellar gait, limb ataxia, or cerebellar oculomotor abnormalities (eg, sustained gaze-evoked nystagmus, square wave macro jerks, hypermetric saccades)
- Palsy of vertical descending supranuclear gaze or selective slowing of vertical descending saccades
- Diagnosis of probable behavioral variant of frontotemporal dementia or primary progressive aphasia, defined according to consensus criteria, within the first 5 years of the disease
- Parkinsonian features limited to the lower limbs for more than 3 years
- Treatment with a dopamine receptor blocker or dopamine-reducing agent at a dose and time consistent with drug-induced parkinsonism
- Absence of observable response to high-dose levodopa despite at least moderate disease severity
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- Unequivocal cortical sensory deficit (i.e., graphesthesia, stereognosis with intact primary sensitivities), clear ideomotor apraxia of limbs, or progressive aphasia
- Normal functional neuroimaging of the presynaptic dopaminergic system
- Documentation of an alternative condition known to induce parkinsonism and plausibly related to the patient's symptoms, or, expert medical opinion that, based on the full diagnostic evaluation, believes that an alternative syndrome is more likely than Parkinson Disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, 00168
Liverana Lauretti, MD
Liverana Lauretti, MD
About this study
Official title: Evaluation of Peripheral Catecholaminergic System in Neurodegenerative Diseases of the Central Nervous System. A Pilot Study.
In several neurodegenerative diseases, such as Parkinson's disease, the progressive loss of neurons of monoaminergic systems leads to the development of characteristic clinical manifestations.
Therefore, since the discovery that neurodegenerative phenomena are the basis of these Central Nervous System (CNS) diseases, re-innervation strategies have been studied that would allow to stop or at least slow down neurodegenerative phenomena, restoring lost catecholaminergic transmission.
Read more
Cell therapy in Parkinson's disease aims to treat motor disorders, but should not affect cognitive disorders that result from pathological alterations external to CNS and affecting other transmission systems, such as noradrenergic and cholinergic. These limitations lead to the search for new approaches based on the use of different cell types, but currently these scenarios still seem far away.
The theme of cerebral re-innervation in the treatment of neurodegenerative diseases is at the center of numerous translational and clinical research studies, developed according to various approaches and models, which testify to all the complexity and charm of the subject. Among the possible sources for a catecholamine reinnervation in Parkinson's disease, Superior Cervical Ganglion (SCG) could represent a valid autologous source: however, there is no functional evaluation in the literature that expresses the involvement or not of the ganglion in the neurodegenerative process.
This clinical study project is the first and essential phase of a larger project aimed at verifying the possibility of autologous catecholamine reinnervation in degenerative diseases of the CNS using the peripheral catecholamine system and in particular the superior cervical ganglion (GCS).
The aim of this project is to evaluate whether the peripheral catecholaminergic system, and in particular the SCG, is involved in the process of neurodegeneration. For this purpose, for an "in vivo" functional study, the suitability of the PET-CT 68Ga-PSMA examination will be studied in particular.
Read the detailed description
- (visit 1) The multidisciplinary team (neurologist, neuroradiologist, nuclear doctor and neurosurgeon) illustrates the research project to the patient eligible for the study: in case of consent to participation, informed consent is signed
- (visit 2) Review of inclusion and exclusion criteria. Neurological evaluation Patients will undergo a complete neurological examination by a neurologist experienced in movement disorders. The inclusion criteria for this study will be verified, including the correctness of the diagnosis according to the MDS diagnostic criteria. The stage of the disease will be quantified with staging according to Hoehn and Yahr. Motor symptoms, the impact of the disease on activities of daily living, neuropsychiatric disorders and the possible presence of motor fluctuations will be quantified with the Unified Parkinson's Disease Rating scale, part I, II, III and IV. In addition, patients will be evaluated with the Mini mental Status Evaluation for cognitive impairment screening. The neurological evaluation will be performed a maximum of three months after the imaging examinations. Neurological evaluation will also be performed on patients in the control group, in order to exclude a diagnosis of PD.
- (visit 3) Neuroradiology The craniocervical MRI protocol includes the sequences: axial T2 and T1 FSE/TSE, coronal T2 FSE/TSE with adipose signal saturation, axial T1 FSE/SE pre- and post-contrast (standard dose of paramagnetic MDC), 3D isotropic T1 with fat saturation, axial DWI (b 0-1000). The acquisition thicknesses will not exceed 3mm with a gap of 10%. 3D-STIR sequences will also be used on the 3T. MRI examination will be performed only on patients in the PD group.
- (visit 4) Nuclear medicine Prostate-specific membrane antigen (PSMA) or glutamate carboxypeptidase II (GCII) is a membrane glycoprotein expressed 100-1000 times more by prostate cancer cells than by other tissues (including benign prostate tissue): its expression increases with increasing stage and grading, and in tumors resistant to antiandrogenic hormone therapy (CRPC). This makes PSMA an ideal target for detecting cancer cells with Positron Emission Tomography (PET). This method is valid in the initial staging of prostate cancer, in the re-evaluation after biochemical recurrence and in the evaluation of the response to treatment. In addition, other non-prostatic malignancies (urothelial carcinoma, bronchial carcinoma, glioblastoma), benign tumors (schwannomas, thyroid adenomas and subcutaneous or vertebral hemangiomas) as well as non-neoplastic tissues (renal tubules, duodenum, colon) have been identified by PET with 68Ga-PSMA by virtue of GCII expression.
Similarly, radiopharmaceutical uptake for PSMA has also been found in celiac, cervicothoracic (stellate) and sacral sympathetic ganglia. Histological studies have demonstrated increased GCII expression by non-myelin Schwann cells of the sympathetic nervous system ganglia . Rather limited in the literature are the studies that have analyzed the physiological greed of 68Ga-PSMA by celiac, stellate and sacral ganglia, as a potential cause of false positive findings on multimodal PET/CT or PET-MR imagin. Moreover, the uptake of 68Ga-PSMA in the superior cervical ganglion (GCS) has been analyzed only in very recent times [1].
In the present study, PET-CT imaging with 68Ga-PSMA will be used to assess the extent to which GCS uptake radiopharmaceutical for PSMA in Parkinson's disease patients. The exam will be performed at the PET Center of the Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Rome. The acquisition of the study will be performed by PET-CT tomograph 80 minutes after the administration of 68Ga-PSMA. The PET images will be evaluated independently by two Nuclear Physicians, after fusion with the MRI images for the correct anatomical localization of the GCS. After a preliminary qualitative (visual) analysis of the radiopharmaceutical uptake, a semi-quantitative evaluation will be carried out by positioning the Volume of Interest (VOI) on each of the GCS in order to calculate the Standardized Uptake Value (SUVmax). These values will be compared with those obtained in patients with prostate cancer undergoing PET-CT with 68Ga-PSMA at the same Center.
- Conditions
- Parkinson Disease
- Being tested
- PET-Neck Parkinsonian patients
- Keywords
- Superior Cervical Ganglion, Catecholaminergic system, Neurodegeneration, Neuroregeneration
- Medical subject headings
- Parkinson Disease, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET-Neck Parkinsonian patientsDiagnostic test
Brain and neck PET-CT scan with 68Ga-PSMA to detect metabolism in the Superior Cervical Ganglion of both sides.
| Study group | Role | What they receive |
|---|---|---|
| PET-Neck Parkinsonian patients | Experimental | Brain and neck PET-CT with 68Ga-PSMA scan would be administered Receives: Diagnostic Test: PET-Neck Parkinsonian patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Capacity of the Superior Cervical Ganglion in parkinsonian patients
The capacity of the Ganglion would be assessed through the analysis of degree of captation (68Ga-CTPET)
Measured: through study completion, an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2023
- Study start1 Jan 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05741151
- Sponsor's protocol ID
- 4656
- Status last verified
- Feb 2023
- First submitted
- 14 Feb 2023
- Last updated
- 1 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Bialek EJ, Malkowski B. Are superior cervical sympathetic ganglia avid on whole body 68Ga-PSMA-11 PET/magnetic resonance?: a comprehensive morphologic and molecular assessment in patients with prostate cancer. Nucl Med Commun. 2019 Nov;40(11):1105-1111. doi: 10.1097/MNM.0000000000001083.
PubMed 31469805
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Peripheral Catecholaminergic System in Neurodegenerative Diseases of the Central Nervous System. A Pilot Study.
- ClinicalTrials.gov ID
- NCT05741151
- Acronym / sponsor ID
- 4656
- Conditions
- Parkinson Disease
- Keywords
- Superior Cervical Ganglion, Catecholaminergic system, Neurodegeneration, Neuroregeneration
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 23 Feb 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.
In several neurodegenerative diseases, such as Parkinson's disease, the progressive loss of neurons of monoaminergic systems leads to the development of characteristic clinical manifestations.
Therefore, since the discovery that neurodegenerative phenomena are the basis of these Central Nervous System (CNS) diseases, re-innervation strategies have been studied that would allow to stop or at least slow down neurodegenerative phenomena, restoring lost catecholaminergic transmission.
Cell therapy in Parkinson's disease aims to treat motor disorders, but should not affect cognitive disorders that result from pathological alterations external to CNS and affecting other transmission systems, such as noradrenergic and cholinergic. These limitations lead to the search for new approaches based on the use of different cell types, but currently these scenarios still seem far away.
The theme of cerebral re-innervation in the treatment of neurodegenerative diseases is at the center of numerous translational and clinical research studies, developed according to various approaches and models, which testify to all the complexity and charm of the subject. Among the possible sources for a catecholamine reinnervation in Parkinson's disease, Superior Cervical Ganglion (SCG) could represent a valid autologous source: however, there is no functional evaluation in the literature that expresses the involvement or not of the ganglion in the neurodegenerative process.
This clinical study project is the first and essential phase of a larger project aimed at verifying the possibility of autologous catecholamine reinnervation in degenerative diseases of the CNS using the peripheral catecholamine system and in particular the superior cervical ganglion (GCS).
The aim of this project is to evaluate whether the peripheral catecholaminergic system, and in particular the SCG, is involved in the process of neurodegeneration. For this purpose, for an "in vivo" functional study, the suitability of the PET-CT 68Ga-PSMA examination will be studied in particular.
Detailed description
- (visit 1) The multidisciplinary team (neurologist, neuroradiologist, nuclear doctor and neurosurgeon) illustrates the research project to the patient eligible for the study: in case of consent to participation, informed consent is signed
- (visit 2) Review of inclusion and exclusion criteria. Neurological evaluation Patients will undergo a complete neurological examination by a neurologist experienced in movement disorders. The inclusion criteria for this study will be verified, including the correctness of the diagnosis according to the MDS diagnostic criteria. The stage of the disease will be quantified with staging according to Hoehn and Yahr. Motor symptoms, the impact of the disease on activities of daily living, neuropsychiatric disorders and the possible presence of motor fluctuations will be quantified with the Unified Parkinson's Disease Rating scale, part I, II, III and IV. In addition, patients will be evaluated with the Mini mental Status Evaluation for cognitive impairment screening. The neurological evaluation will be performed a maximum of three months after the imaging examinations. Neurological evaluation will also be performed on patients in the control group, in order to exclude a diagnosis of PD.
- (visit 3) Neuroradiology The craniocervical MRI protocol includes the sequences: axial T2 and T1 FSE/TSE, coronal T2 FSE/TSE with adipose signal saturation, axial T1 FSE/SE pre- and post-contrast (standard dose of paramagnetic MDC), 3D isotropic T1 with fat saturation, axial DWI (b 0-1000). The acquisition thicknesses will not exceed 3mm with a gap of 10%. 3D-STIR sequences will also be used on the 3T. MRI examination will be performed only on patients in the PD group.
- (visit 4) Nuclear medicine Prostate-specific membrane antigen (PSMA) or glutamate carboxypeptidase II (GCII) is a membrane glycoprotein expressed 100-1000 times more by prostate cancer cells than by other tissues (including benign prostate tissue): its expression increases with increasing stage and grading, and in tumors resistant to antiandrogenic hormone therapy (CRPC). This makes PSMA an ideal target for detecting cancer cells with Positron Emission Tomography (PET). This method is valid in the initial staging of prostate cancer, in the re-evaluation after biochemical recurrence and in the evaluation of the response to treatment. In addition, other non-prostatic malignancies (urothelial carcinoma, bronchial carcinoma, glioblastoma), benign tumors (schwannomas, thyroid adenomas and subcutaneous or vertebral hemangiomas) as well as non-neoplastic tissues (renal tubules, duodenum, colon) have been identified by PET with 68Ga-PSMA by virtue of GCII expression.
Similarly, radiopharmaceutical uptake for PSMA has also been found in celiac, cervicothoracic (stellate) and sacral sympathetic ganglia. Histological studies have demonstrated increased GCII expression by non-myelin Schwann cells of the sympathetic nervous system ganglia . Rather limited in the literature are the studies that have analyzed the physiological greed of 68Ga-PSMA by celiac, stellate and sacral ganglia, as a potential cause of false positive findings on multimodal PET/CT or PET-MR imagin. Moreover, the uptake of 68Ga-PSMA in the superior cervical ganglion (GCS) has been analyzed only in very recent times [1].
In the present study, PET-CT imaging with 68Ga-PSMA will be used to assess the extent to which GCS uptake radiopharmaceutical for PSMA in Parkinson's disease patients. The exam will be performed at the PET Center of the Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Rome. The acquisition of the study will be performed by PET-CT tomograph 80 minutes after the administration of 68Ga-PSMA. The PET images will be evaluated independently by two Nuclear Physicians, after fusion with the MRI images for the correct anatomical localization of the GCS. After a preliminary qualitative (visual) analysis of the radiopharmaceutical uptake, a semi-quantitative evaluation will be carried out by positioning the Volume of Interest (VOI) on each of the GCS in order to calculate the Standardized Uptake Value (SUVmax). These values will be compared with those obtained in patients with prostate cancer undergoing PET-CT with 68Ga-PSMA at the same Center.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PET-Neck Parkinsonian patients | Experimental | Diagnostic Test: PET-Neck Parkinsonian patientsBrain and neck PET-CT with 68Ga-PSMA scan would be administered |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients affected with Parkinson Disease according to the criteria defined by the Movements Disorder Society
Key exclusion criteria (9 listed)
- Unambiguous cerebellar abnormalities, such as cerebellar gait, limb ataxia, or cerebellar oculomotor abnormalities (eg, sustained gaze-evoked nystagmus, square wave macro jerks, hypermetric saccades)
- Palsy of vertical descending supranuclear gaze or selective slowing of vertical descending saccades
- Diagnosis of probable behavioral variant of frontotemporal dementia or primary progressive aphasia, defined according to consensus criteria, within the first 5 years of the disease
- Parkinsonian features limited to the lower limbs for more than 3 years
- Treatment with a dopamine receptor blocker or dopamine-reducing agent at a dose and time consistent with drug-induced parkinsonism
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 |
|---|---|---|
| PET-Neck Parkinsonian patientsBrain and neck PET-CT scan with 68Ga-PSMA to detect metabolism in the Superior Cervical Ganglion of both sides. | Diagnostic test | PET-Neck Parkinsonian patients |
Primary outcome
Capacity of the Superior Cervical Ganglion in parkinsonian patients
Time frame: through study completion, an average of 3 years
The capacity of the Ganglion would be assessed through the analysis of degree of captation (68Ga-CTPET)
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 1 Mar 2023.
- Results publication: PubMed 31469805Bialek EJ, Malkowski B. Are superior cervical sympathetic ganglia avid on whole body 68Ga-PSMA-11 PET/magnetic resonance?: a comprehensive morphologic and molecular assessment in patients with prostate cancer. Nucl Med Commun. 2019 Nov;40(11):1105-1111. doi: 10.1097/MNM.0000000000001083.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PET-Neck Parkinsonian patients in people with Parkinson Disease, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
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 1 inclusion and 9 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 1 Mar 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 Italy. 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 Liverana Lauretti, MD (+39 06 3015 5031, Liverana.Lauretti@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Capacity of the Superior Cervical Ganglion in parkinsonian patients (time frame: through study completion, an average of 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05741151, which also lists 1 linked publication.
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 1 Mar 2023.