Neuro-Degenerative DiseaseNeuroInfiamNCT03918616
P2X7 Receptor, Inflammation and Neurodegenerative Diseases
An observational study of Neuro-Degenerative Disease, run by University of Pisa at 1 site in Italy.
Trial summary
Parkinson disease (PD) is a chronic degenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Its pathophysiological mechanisms are still partially unknown; a main role seems to be played by chronic neuroinflammation. Read more about this study
- Who is it for?
- Ages 45 to 80 years
- Conditions the study is for
- Neuro-Degenerative Disease
- What is being tested?
- Memantine, Dopamine receptor-agonists
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 20 Feb 2017to 30 Mar 2019
- Phase
- Observational
- 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 45 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study consecutively enrolled 50 newly-diagnosed, treatment-naive PD or AD individuals among those referring to the Neurology Unit, University Hospital in Pisa, Italy.
Who may be able to join
- newly-diagnosed PD or AD;
- no previous specific treatment;
- no systemic inflammatory or immunological disease and/or cancer;
- no anti-inflammatory drugs assumed in the three months preceding the enrolment;
- patients able to consent.
Who cannot join
- history of strokes or any neurological disease;
- patients assuming neuroleptic drugs;
- atypical symptoms at onset.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: P2X7 Receptor, Inflammation and Pathophysiology of Neurodegenerative Diseases
Parkinson disease (PD) is a chronic degenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Its pathophysiological mechanisms are still partially unknown; a main role seems to be played by chronic neuroinflammation. A few reports have addressed the possible involvement of the inflammasome in PD, just describing the protective effect of P2X7 purinergic receptor (P2X7R) blockers in murine models of the disease and in microglial cells, where NLRP3 is activated by α-Synuclein, triggering a neuroinflammation that contributes to degeneration of dopaminergic neurons. It is still unclear whether, in addition to the increased brain expression and function of the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing type 3 (NLRP3) inflammasome platform, a systemic activation of such complex might participate in the pathogenesis of PD, which could be the role of the P2X7R in this scenario, and whether such patterns undergo any specific epigenetic regulation. The present study has been designed to address these issues.
Read the detailed description
The day of the study patientes underwent a complete clinical evaluation and assessment of psycho-physical abilities using specific test such as Mini-Mental State Examination (MMSE), Cognitive Alzheimer's Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS). Blood samples were collected from an antecubital vein to assess serum and plasma aliquots for blood routine analysis and RNA and protein extraction from circulating lymphomonocytes.
To explore a putative epigenetic regulation of such complex scenario some circulating miRNAs likely involved in the pathogenesis of neurological diseases and neuro-inflammation will be measured.
Expression and functional activity of P2X7R-inflammasome complex will be measured by PCR and WB. Acute phase cytokines inflammasome-related levels will be determined by ELISA. Biochemical parameters (fasting glucose, lipid profile, serum creatinine, uric acid) will be measured by standard methods in the biochemistry laboratory of the University Hospital in Pisa. The same determinations will be repeated after one year from the first visit.
- Conditions
- Neuro-Degenerative Disease
- Being tested
- Memantine, Dopamine receptor-agonists
- Keywords
- Alzheimer disease, Parkinson disease, P2X7 receptor
- Medical subject headings
- Alzheimer Disease, Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Memantine, Dopamine receptor-agonistsDrug
Also called Memantine: Ebixa. Dopamine receptor-agonists: Sinemet, Sirio.
The study do not provide any experimental drugs. Patientes will receive treatment routinary used by Neurologist for these diseases.
| Study group | Role | What they receive |
|---|---|---|
| PD + AD | Patients with newly-diagnosed (onset of suggestive symptoms not later than 3 months) Parkinson disease (PD) or Alzheimer disease (AD) with no previous specific treatment, no anti-inflammatory drugs assumed in the three months preceding the enrolment and no chronic inflammatory diseases or cancer. Receives: Drug: Memantine, Dopamine receptor-agonists | |
| Control group | An age and gender matched control group (n=50) was formed, on a volunteer basis, by the spouse of the probands participating in the study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in P2X7R-inflammasome activity
NLRP3-ASC-Caspase-1 activity is measured using RT-PCR
Measured: each patient will be assessed one year after diagnosis
Change from baseline in NFkB activity
NFkB activity is measured using RT-PCR
Measured: each patient will be assessed one year after diagnosis
Change from baseline in serum α-synuclein
Circulating levels of α-synuclein are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as [ng/ml]
Measured: each patient will be assessed one year after diagnosis
Change from baseline in serum IL-1β
Circulating levels of IL-1β are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as [pg/ml]
Measured: each patient will be assessed one year after diagnosis
Change from baseline in serum IL-18
Circulating levels of IL-18 are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as [pg/ml]
Measured: each patient will be assessed one year after diagnosis
Change from baseline in circulating levels of microRNA miR-30 and miR-7
Circulating levels of microRNA miR-30 and miR-7 are measured using TaqMan Advanced MicroRNA Assays
Measured: each patient will be assessed one year after diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2019
- Study start20 Feb 2017
- Primary completion30 Dec 2018
- Study completion30 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuro-Degenerative DiseaseStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pisa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anna Solini, University of Pisa
- Investigators
- Anna Solini, MD, PhD, Principal investigator, Univeristy of Pisa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03918616
- Sponsor's protocol ID
- AS0002
- Acronym
- NeuroInfiam
- Status last verified
- Aug 2019
- First submitted
- 10 Apr 2019
- Last updated
- 13 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- P2X7 Receptor, Inflammation and Pathophysiology of Neurodegenerative Diseases
- ClinicalTrials.gov ID
- NCT03918616
- Acronym / sponsor ID
- NeuroInfiam / AS0002
- Conditions
- Neuro-Degenerative Disease
- Keywords
- Alzheimer disease, Parkinson disease, P2X7 receptor
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of PisaUniversity, hospital or other
- Study start
- 20 Feb 2017 (actual)
- Primary completion
- 30 Dec 2018 (actual)
- Study completion
- 30 Mar 2019 (actual)
- First posted
- 17 Apr 2019 (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.
Parkinson disease (PD) is a chronic degenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Its pathophysiological mechanisms are still partially unknown; a main role seems to be played by chronic neuroinflammation. A few reports have addressed the possible involvement of the inflammasome in PD, just describing the protective effect of P2X7 purinergic receptor (P2X7R) blockers in murine models of the disease and in microglial cells, where NLRP3 is activated by α-Synuclein, triggering a neuroinflammation that contributes to degeneration of dopaminergic neurons. It is still unclear whether, in addition to the increased brain expression and function of the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing type 3 (NLRP3) inflammasome platform, a systemic activation of such complex might participate in the pathogenesis of PD, which could be the role of the P2X7R in this scenario, and whether such patterns undergo any specific epigenetic regulation. The present study has been designed to address these issues.
Detailed description
The day of the study patientes underwent a complete clinical evaluation and assessment of psycho-physical abilities using specific test such as Mini-Mental State Examination (MMSE), Cognitive Alzheimer's Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS). Blood samples were collected from an antecubital vein to assess serum and plasma aliquots for blood routine analysis and RNA and protein extraction from circulating lymphomonocytes.
To explore a putative epigenetic regulation of such complex scenario some circulating miRNAs likely involved in the pathogenesis of neurological diseases and neuro-inflammation will be measured.
Expression and functional activity of P2X7R-inflammasome complex will be measured by PCR and WB. Acute phase cytokines inflammasome-related levels will be determined by ELISA. Biochemical parameters (fasting glucose, lipid profile, serum creatinine, uric acid) will be measured by standard methods in the biochemistry laboratory of the University Hospital in Pisa. The same determinations will be repeated after one year from the first visit.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PD + AD | – | Drug: Memantine, Dopamine receptor-agonistsPatients with newly-diagnosed (onset of suggestive symptoms not later than 3 months) Parkinson disease (PD) or Alzheimer disease (AD) with no previous specific treatment, no anti-inflammatory drugs assumed in the three months preceding the enrolment and no chronic inflammatory diseases or cancer. |
| Control group | – | –An age and gender matched control group (n=50) was formed, on a volunteer basis, by the spouse of the probands participating in the study. |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study consecutively enrolled 50 newly-diagnosed, treatment-naive PD or AD individuals among those referring to the Neurology Unit, University Hospital in Pisa, Italy.
Key inclusion criteria (5 listed)
- newly-diagnosed PD or AD;
- no previous specific treatment;
- no systemic inflammatory or immunological disease and/or cancer;
- no anti-inflammatory drugs assumed in the three months preceding the enrolment;
- patients able to consent.
Key exclusion criteria (3 listed)
- history of strokes or any neurological disease;
- patients assuming neuroleptic drugs;
- atypical symptoms at onset.
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 |
|---|---|---|
| Memantine, Dopamine receptor-agonistsAlso: Memantine: Ebixa. Dopamine receptor-agonists: Sinemet, Sirio.The study do not provide any experimental drugs. Patientes will receive treatment routinary used by Neurologist for these diseases. | Drug | PD + AD |
Primary outcome
Change from baseline in P2X7R-inflammasome activity
Time frame: each patient will be assessed one year after diagnosis
NLRP3-ASC-Caspase-1 activity is measured using RT-PCR
Change from baseline in NFkB activity
Time frame: each patient will be assessed one year after diagnosis
NFkB activity is measured using RT-PCR
Change from baseline in serum α-synuclein
Time frame: each patient will be assessed one year after diagnosis
Circulating levels of α-synuclein are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as [ng/ml]
Change from baseline in serum IL-1β
Time frame: each patient will be assessed one year after diagnosis
Circulating levels of IL-1β are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as [pg/ml]
Change from baseline in serum IL-18
Time frame: each patient will be assessed one year after diagnosis
Circulating levels of IL-18 are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as [pg/ml]
Change from baseline in circulating levels of microRNA miR-30 and miR-7
Time frame: each patient will be assessed one year after diagnosis
Circulating levels of microRNA miR-30 and miR-7 are measured using TaqMan Advanced MicroRNA Assays
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2019.
Related trials for Neuro-Degenerative Disease
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
Recruiting
Informational Needs of Caregivers of Patients With Neuromotor Disease in Rehabilitation Hospitalization: Validation Study of the QBI-R/V
Neuro-Degenerative Diseases, Care Givers
RecruitingPhase 2
Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders
Langerhan's Cell Histiocytosis, Juvenile Xanthogranuloma
Enrolling by invitationObservational study
Białystok PLUS - Polish Longitudinal University Study
Cardiovascular Diseases, Diabetes
Not yet recruitingPhase 1/2
C-CAR168, an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T-Cell Therapy, in Participants With Progressive Multiple Sclerosis Refractory to Standard Therapy
Multiple Sclerosis, Primary Progressive Multiple Sclerosis
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.
Anna Solini, MD, PhD principal investigator
Univeristy of Pisa
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 Neuro-Degenerative Disease, run by University of Pisa 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 5 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: finished, as of the sponsor's last update on 13 Aug 2019. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in P2X7R-inflammasome activity (time frame: each patient will be assessed one year after diagnosis). The study lists 6 primary outcomes in all. 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 13 Aug 2019.