Parkinson's DiseaseIBIM-ParkNCT04652843
Single-center Pathophysiological Study of the Role of Inflammation, Changes in the Intestinal Epithelial Barrier and the Intestinal Microbiota in Parkinson's Disease
A study testing Rectosignoidoscopy and Coloscopy in people with Parkinson's Disease, run by Nantes University Hospital at 1 site in France.
Trial summary
Converging evidence from the literature suggests that digestive inflammation may play a role in the development of Parkinson's disease (PD). The investigators showed in the laboratory in a pilot study that PD patients have digestive inflammation and that the level of inflammation was inversely related to the length of… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Rectosignoidoscopy and Coloscopy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 1 siteFrance
- Study dates
- 17 Dec 2020to 12 Jan 2024
- Phase
- Interventional
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Parkinson's Disease patients :
- patients with Parkinson's disease according to the criteria of the United Kingdom Parkinson's disease survey brain bank (UKPDSBB)
- aged over 18 years
- who have given their consent to participate in this study
- Idiopathic REM sleep behavior disorders patients:
- patients with an Idiopathic REM sleep behavior disorder confirmed by video-polysomnography (International Classification of Sleep Disorders-3 criteria), not explained by a pathology (narcolepsy, brainstem injury, neurodegenerative disease)
Show all 12Show fewer
- aged over 18 years
- having given their consent to participate in this study
- Control:
- patients undergoing coloscopy for family screening for digestive polyps
- aged over 18
- who have given their consent to participate in this study
Who cannot join
- dementia (MINI MENTAL STATE EXAMINATION score <24)
- history of authenticated colonic disease (inflammatory disease, adenocarcinoma) or functional colopathy in control subjects or having preceded the first signs of Parkinson's Disease or Idiopathic REM sleep behavior disorder for more than 5 years, respectively in Parkinson's Disease and Idiopathic REM sleep behavior disorder patients
- history of prescription of antibiotic treatment, acute gastrointestinal illness or hospitalization for an acute medical pathology or for a surgical procedure in the last month
- anticoagulant treatment or coagulopathy
- pregnant or breastfeeding women, woman not benefiting from effective contraception if of childbearing age
- adults under tutorship, curatorship or under legal protection
Show all 11Show fewer
- For patients with Idiopathic REM sleep behavior disorder:
- presence of Parkinson's Disease according to United Kindom Parkinson's Disease Brain Bank criteria
- For control:
- presence of a Parkinson's Disease according to United Kindom Parkinson's Disease Brain Bank criteria
- complaint of nighttime unrest in favor of a probable Idiopathic REM sleep behavior disorder
Trial locations and contacts
1 site in 1 country.
About this study
Converging evidence from the literature suggests that digestive inflammation may play a role in the development of Parkinson's disease (PD). The investigators showed in the laboratory in a pilot study that PD patients have digestive inflammation and that the level of inflammation was inversely related to the length of the disease course. This digestive inflammation could be at the origin of an increased intestinal permeability in a subpopulation of parkinsonian patients, cause or consequence of modifications of the intestinal microbiota, thus offering a potential portal of entry for a pathogen according to Braak's theory. To opponents of this theory, it could also reflect the spread of inflammation from the Central nervous System to the Enteral Nervous System (ENS), via the brain-gut axis.
Investigators' hypothesis is that digestive inflammation occurs very early in Parkinson's disease and that it is associated with hyperpermeability of the intestinal epithelial barrier and a change in the intestinal microbiota composition. The investigators propose to study the inflammation markers in the ENS of patients with a pre-motor form of PD (idiopathic Rapid Eye Movement (REM) sleep behavior disorder, n = 20), early-stage PD (<5 years, without dopatherapy, n = 20), more advanced PD (> 5 years, n = 20) and control subjects (n = 20), on colonic biopsies taken during a rectosigmoidoscopy or a coloscopy. Intestinal permeability will be measured by ex-vivo techniques (in a Ussing chamber), the composition of the microbiota will be established by sequencing 16s RNA and the lesional load of phosphorylated alpha-synuclein will be evaluated by immunohistochemistry. All of these parameters will be correlated with clinical data on the severity of PD: duration of development, age, total Unified Parkinson's Disease Rating Scale (UPDRS) motor score and axial sub-score, cognitive tests (Montreal Cognitive Assessment, MoCA), existence of a probable idiopathic REM sleep behavior disorder (REM Sleep Behavior Disorder Screening Questionnaire RBDSQ), olfactory tests, complaint of dysautonomia (SCales for Outcomes in Parkinson's disease - autonomic dysfunction, SCOPA-Aut).
The analysis of inflammation markers, the intestinal barrier and the microbiota could be a first step making it possible to formulate physiopathological hypotheses on the development of PD, to propose predictive biomarkers of the disease and its severity and to design early interventions in the hope of modifying the evolutionary course of the pathological process.
- Conditions
- Parkinson's Disease
- Being tested
- Rectosignoidoscopy, Coloscopy
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RectosignoidoscopyProcedure or surgery
Rectosignoidoscopy for colonic biospsies collection
ColoscopyProcedure or surgery
Coloscopy for colonic biospsies collection
| Study group | Role | What they receive |
|---|---|---|
| Idiopathic REM sleep behavior disorders | Other | Group of 20 Patients with an Idiopathic REM sleep behavior disorder confirmed by video-polysomnography (International Classification of Sleep Disorders-3 criteria), not explained by a pathology (narcolepsy, brainstem injury, neurodegenerative disease) Receives: Procedure: Rectosignoidoscopy; Procedure: Coloscopy |
| Beginning Parkinson's disease | Other | Group of 20 patients with Parkinson's Disease which has been progressing for less than 5 years and who have not received dopatherapy Receives: Procedure: Rectosignoidoscopy; Procedure: Coloscopy |
| Parkinson's disease state Phase | Other | Group of 20 patients with Parkinson's Disease for more than 5 years Receives: Procedure: Rectosignoidoscopy; Procedure: Coloscopy |
| Control | Other | Group of 20 patients undergoing coloscopy for family screening for digestive polyps Receives: Procedure: Coloscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
TNF-α
TNF-α in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
Secondary outcomes (24)
IFN-γ
IFN-γ in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
IL-6
IL-6 in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
IL-1β
IL-1β in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
IFN-α2
IFN-α2 in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
MCP-1 (CCL2)
MCP-1 (CCL2) in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
IL-8 (CXCL8)
IL-8 (CXCL8) in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
IL-10
IL-10 in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
IL-12p70
IL-12p70 in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
IL-17A
IL-17A in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
IL-18
IL-18 in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
IL-23
IL-23 in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
IL-33
IL-33 in colonic biopsies measured by ELISA
Measured: In the three months following the inclusion
Permeability slopes for sulfonic acid
Permeability slopes for sulfonic acid (low molecular weight) and dextran (high molecular weight) measured in a Ussing chamber
Measured: In the three months following the inclusion
Diversity of the intestinal microbiota
Bacterial diversity in each group by genetic sequencing of 16s RNA
Measured: In the three months following the inclusion
Relative abundance of the intestinal microbiota
Relative abundance of different families or genera or bacterial species in each group by genetic sequencing of 16s RNA
Measured: In the three months following the inclusion
Quantification of phosphorylated alpha-synuclein
Presence or absence of inclusion of phosphorylated alpha-synuclein, if presence: quantification (in thioflavin fluorescence intensity and amplification time in minutes)
Measured: In the three months following the inclusion
Duration of progression
Disease duration of progression as Parkinson's disease clinical severity parameter
Measured: At inclusion
Age
Age as Parkinson's disease clinical severity parameter
Measured: At inclusion
Total Unified Parkinson Disease Rating Scale motor score
Total Unified Parkinson Disease Rating Scale motor score as Parkinson's disease clinical severity parameter
Measured: At inclusion
Unified Parkinson Disease Rating Scale axial sub-score
Unified Parkinson Disease Rating Scale axial sub-score as Parkinson's disease clinical severity parameter
Measured: At inclusion
Montreal Cognitive Assessment score
Montreal Cognitive Assessment score as Parkinson's disease clinical severity parameter
Measured: At inclusion
Presence or absence of a probable Idiopathic REM sleep behavior disorders
Presence or absence of a probable Idiopathic REM sleep behavior disorders (REM Sleep Behavior Disorder Screening Questionnaire score ≥ 5) as Parkinson's disease clinical severity parameter
Measured: At inclusion
Olfactory tests
Olfactory tests (Sniffin 'sticks test score) as Parkinson's disease clinical severity parameter
Measured: At inclusion
Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction score
Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction score as Parkinson's disease clinical severity parameter
Measured: At inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2020
- Study start17 Dec 2020
- Primary completion12 Jan 2024
- Study completion12 Jan 2024
Why it stopped: Despite an extension of the planned duration of inclusion and an enrolled patient number inferior than planned, coordinating investigator considered that it was more reasonable to stop inclusions in order to analyze the data already available
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- France Parkinson Association, Luxia Scientific, Institut National de la Santé Et de la Recherche Médicale, France
- Responsible party
- Sponsor
- Investigators
- Laurène LECLAIR-VISONNEAU, MD, Principal investigator, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04652843
- Sponsor's protocol ID
- RC19_0401
- Acronym
- IBIM-Park
- Status last verified
- Jan 2024
- First submitted
- 25 Nov 2020
- Last updated
- 1 Feb 2024
- 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 1 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-center Pathophysiological Study of the Role of Inflammation, Changes in the Intestinal Epithelial Barrier and the Intestinal Microbiota in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT04652843
- Acronym / sponsor ID
- IBIM-Park / RC19_0401
- Conditions
- Parkinson's Disease
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Despite an extension of the planned duration of inclusion and an enrolled patient number inferior than planned, coordinating investigator considered that it was more reasonable to stop inclusions in order to analyze the data already available
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Collaborators
- France Parkinson Association, Luxia Scientific, Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- 17 Dec 2020 (actual)
- Primary completion
- 12 Jan 2024 (actual)
- Study completion
- 12 Jan 2024 (actual)
- First posted
- 3 Dec 2020 (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.
Converging evidence from the literature suggests that digestive inflammation may play a role in the development of Parkinson's disease (PD). The investigators showed in the laboratory in a pilot study that PD patients have digestive inflammation and that the level of inflammation was inversely related to the length of the disease course. This digestive inflammation could be at the origin of an increased intestinal permeability in a subpopulation of parkinsonian patients, cause or consequence of modifications of the intestinal microbiota, thus offering a potential portal of entry for a pathogen according to Braak's theory. To opponents of this theory, it could also reflect the spread of inflammation from the Central nervous System to the Enteral Nervous System (ENS), via the brain-gut axis.
Investigators' hypothesis is that digestive inflammation occurs very early in Parkinson's disease and that it is associated with hyperpermeability of the intestinal epithelial barrier and a change in the intestinal microbiota composition. The investigators propose to study the inflammation markers in the ENS of patients with a pre-motor form of PD (idiopathic Rapid Eye Movement (REM) sleep behavior disorder, n = 20), early-stage PD (<5 years, without dopatherapy, n = 20), more advanced PD (> 5 years, n = 20) and control subjects (n = 20), on colonic biopsies taken during a rectosigmoidoscopy or a coloscopy. Intestinal permeability will be measured by ex-vivo techniques (in a Ussing chamber), the composition of the microbiota will be established by sequencing 16s RNA and the lesional load of phosphorylated alpha-synuclein will be evaluated by immunohistochemistry. All of these parameters will be correlated with clinical data on the severity of PD: duration of development, age, total Unified Parkinson's Disease Rating Scale (UPDRS) motor score and axial sub-score, cognitive tests (Montreal Cognitive Assessment, MoCA), existence of a probable idiopathic REM sleep behavior disorder (REM Sleep Behavior Disorder Screening Questionnaire RBDSQ), olfactory tests, complaint of dysautonomia (SCales for Outcomes in Parkinson's disease - autonomic dysfunction, SCOPA-Aut).
The analysis of inflammation markers, the intestinal barrier and the microbiota could be a first step making it possible to formulate physiopathological hypotheses on the development of PD, to propose predictive biomarkers of the disease and its severity and to design early interventions in the hope of modifying the evolutionary course of the pathological process.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Idiopathic REM sleep behavior disorders | Other | Procedure: Rectosignoidoscopy, Procedure: ColoscopyGroup of 20 Patients with an Idiopathic REM sleep behavior disorder confirmed by video-polysomnography (International Classification of Sleep Disorders-3 criteria), not explained by a pathology (narcolepsy, brainstem injury, neurodegenerative disease) |
| Beginning Parkinson's disease | Other | Procedure: Rectosignoidoscopy, Procedure: ColoscopyGroup of 20 patients with Parkinson's Disease which has been progressing for less than 5 years and who have not received dopatherapy |
| Parkinson's disease state Phase | Other | Procedure: Rectosignoidoscopy, Procedure: ColoscopyGroup of 20 patients with Parkinson's Disease for more than 5 years |
| Control | Other | Procedure: ColoscopyGroup of 20 patients undergoing coloscopy for family screening for digestive polyps |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- patients with Parkinson's disease according to the criteria of the United Kingdom Parkinson's disease survey brain bank (UKPDSBB)
- aged over 18 years
- who have given their consent to participate in this study
- patients with an Idiopathic REM sleep behavior disorder confirmed by video-polysomnography (International Classification of Sleep Disorders-3 criteria), not explained by a pathology (narcolepsy, brainstem injury, neurodegenerative disease)
- aged over 18 years
Key exclusion criteria (11 listed)
- dementia (MINI MENTAL STATE EXAMINATION score <24)
- history of authenticated colonic disease (inflammatory disease, adenocarcinoma) or functional colopathy in control subjects or having preceded the first signs of Parkinson's Disease or Idiopathic REM sleep behavior disorder for more than 5 years, respectively in Parkinson's Disease and Idiopathic REM sleep behavior disorder patients
- history of prescription of antibiotic treatment, acute gastrointestinal illness or hospitalization for an acute medical pathology or for a surgical procedure in the last month
- anticoagulant treatment or coagulopathy
- pregnant or breastfeeding women, woman not benefiting from effective contraception if of childbearing age
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 |
|---|---|---|
| RectosignoidoscopyRectosignoidoscopy for colonic biospsies collection | Procedure or surgery | Beginning Parkinson's disease, Idiopathic REM sleep behavior disorders, Parkinson's disease state Phase |
| ColoscopyColoscopy for colonic biospsies collection | Procedure or surgery | Beginning Parkinson's disease, Control, Idiopathic REM sleep behavior disorders, Parkinson's disease state Phase |
Primary outcome
TNF-α
Time frame: In the three months following the inclusion
TNF-α in colonic biopsies measured by ELISA
24 secondary outcomes
IFN-γ
Time frame: In the three months following the inclusion
IL-6
Time frame: In the three months following the inclusion
IL-1β
Time frame: In the three months following the inclusion
IFN-α2
Time frame: In the three months following the inclusion
MCP-1 (CCL2)
Time frame: In the three months following the inclusion
IL-8 (CXCL8)
Time frame: In the three months following the inclusion
IL-10
Time frame: In the three months following the inclusion
IL-12p70
Time frame: In the three months following the inclusion
IL-17A
Time frame: In the three months following the inclusion
IL-18
Time frame: In the three months following the inclusion
IL-23
Time frame: In the three months following the inclusion
IL-33
Time frame: In the three months following the inclusion
Permeability slopes for sulfonic acid
Time frame: In the three months following the inclusion
Diversity of the intestinal microbiota
Time frame: In the three months following the inclusion
Relative abundance of the intestinal microbiota
Time frame: In the three months following the inclusion
Quantification of phosphorylated alpha-synuclein
Time frame: In the three months following the inclusion
Duration of progression
Time frame: At inclusion
Age
Time frame: At inclusion
Total Unified Parkinson Disease Rating Scale motor score
Time frame: At inclusion
Unified Parkinson Disease Rating Scale axial sub-score
Time frame: At inclusion
Montreal Cognitive Assessment score
Time frame: At inclusion
Presence or absence of a probable Idiopathic REM sleep behavior disorders
Time frame: At inclusion
Olfactory tests
Time frame: At inclusion
Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction score
Time frame: At inclusion
Results and safety
The study was stopped early (reason given: Despite an extension of the planned duration of inclusion and an enrolled patient number inferior than planned, coordinating investigator considered that it was more reasonable to stop inclusions in order to analyze the data already available). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2024.
- Individual participant dataSharing planned: No
Related trials for Parkinson's Disease
Enrolling by invitationObservational study
Early Molecular Biomarkers for Differentiating Parkinsonian Syndromes
PARKINSON DISEASE (Disorder), Atypical Parkinsonism
Active, not recruitingPhase 1/2
Clinical Safety and Efficacy of Umbilical Cord Mesenchymal Stromal Cells-derived Exosomes in Patients With Parkinson's Disease
Parkinson Disease (PD)
Active, not recruitingObservational study
Adaptive DBS to Offset STN Dysregulation During Exercise in PD
Parkinson Disease
Not yet recruiting
Compulsive Eating and Brain's Reward System in Different Pathologies
PARKINSON DISEASE (Disorder), Bipolar 1 Disorder
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
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.
Laurène LECLAIR-VISONNEAU, MD principal investigator
Nantes University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rectosignoidoscopy and Coloscopy in people with Parkinson's Disease, run by Nantes University Hospital at 1 site in France.
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 12 inclusion and 11 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: stopped early, as of the sponsor's last update on 1 Feb 2024. 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 France. 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 was stopped early (reason given: Despite an extension of the planned duration of inclusion and an enrolled patient number inferior than planned, coordinating investigator considered that it was more reasonable to stop inclusions in order to analyze the data already available). Results are not available in the source record.
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?
TNF-α (time frame: In the three months following the inclusion). 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 1 Feb 2024.