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Clinical Trial for Near Infrared Endoventricular Illumination for Neuroprotection in Very Early Cases of Parkinson's Disease (Ev-NIRT) (Ev-NIRT)

Primary Purpose

Very Early Stage of Parkinson's Disease

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Ev-NIRT
Sponsored by
University Hospital, Grenoble
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Very Early Stage of Parkinson's Disease focused on measuring Parkinson's disease (PD), Intraventricular illumination by near-infrared light (Ev-NIRT), Positron Emission Tomography (PET), Substantia Nigra Pars Compacta (SNpc), Photobiomodulation, Medical Device (MD)

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Clinically diagnosed idiopathic Parkinson's disease according to MDS criteria developed by R.B. Postuma (Anang et al, Neurology, 2014)
  2. Dopaminergic denervation confirmed in PET [11C]PE2I with a decrease in tracer fixation at the striatum level of at least 30% on average compared to the white matter fixation of the cerebellum
  3. Patients willing to start dopaminergic treatment

  4. Very early stage of the disease:

    1. Diagnosis of recent Parkinson's disease (less than two years after a neurologist's diagnosis)
    2. Hoehn and Yahr Stage 1 to 2
    3. Maximum 2 tremor on the MDS-UPDRS scale
    4. Naive of any anti-Parkinsonian treatment
  5. Between 25 and 65 years of age
  6. Score on Beck Depression Inventory (BDI) scale below the value of 20
  7. Easy handling of the French language in oral and written language
  8. Social security affiliates or beneficiaries of such a scheme
  9. Informed and written consent signed by the patient

Exclusion Criteria:

  1. All categories of protected persons: pregnant woman, parturient, breastfeeding mother, person deprived of liberty by judicial or administrative decision, person subject to a measure of legal protection, hospitalized for psychiatric disorder
  2. Carcinological history in the previous 5 years, not stabilized
  3. Uncontrolled medical condition that may lead to complications
  4. Preoperative brain Magnetic Resonance Imaging (MRI) showing brain damage that may be responsible for Parkinson's syndrome or a significant surgical risk (e.g. vascular malformation)
  5. Surgical or anesthetic contraindication
  6. History of brain infection with herpes virus
  7. Contraindication to MRI (claustrophobia, non-compatible mri metal prosthesis, etc.)
  8. Predictable need for frequent use of MRI scans after surgery
  9. Unstabilized psychotropic treatment
  10. Patient with cognitive impairment at the outset of illness (Montreal Cognitive Assessment (MoCA) score - 26)
  11. Atypias suspecting atypical Parkinson's syndrome
  12. Chronic treatment with L-Dopa or dopamine agonist
  13. Presence of another serious pathology (major depressive episode, suicidal patient, active psychosis ...)
  14. Participation in another interventional clinical trial
  15. Wearing pace makers other than brain

Sites / Locations

  • CLINATECRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Illuminated arm

control arm

Arm Description

patients with intraventricular near-infrared light illumination

patients without any medical device

Outcomes

Primary Outcome Measures

Incidence of Ev-NIRT Treatment on Emergent Adverse Events (Tolerance) after surgical intervention and NIR illumination following the implantation of the Ev-NIRT medical device
Emergent Adverse Events [Safety and Tolerability]

Secondary Outcome Measures

Characterization of annual neuronal loss observed by decrease in tracer fixation at the striatum level
Annual measurement of dopaminergic denervation in Positron Emission Tomography (PET) using [11C]PE2I tracer fixation at the striatum level in percentage compared to the white matter fixation of the cerebellum
Evaluation of the motor clinical signs progression
Scores on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS scale sections II, III and IV) [0-100% : higher scores mean worse outcome]
Evaluation of the non-motor bahavioral signs progression
Scores on the non-motor scales Behavioral Evaluation in Parkinson's disease (ECMP) [0-4 : higher scores mean worse outcome]
Evaluation of the non-motor clinical signs progression
Scores on the non-motor scales Lille Apathy Rating Scale (LARS) [-4/+4 : higher scores mean worse outcome]
Evaluation of depression signs progression
Scores on the non-motor scales Beck Depression Inventory (BDI-II) [0-3 : higher scores mean worse outcome]
Evaluation of the non-motor symptoms signs progression
Scores on the non-motor scales Non Motor Symptoms scale (NMS) [0-30 : higher scores mean better outcome]
Comparison between the date of diagnosis and the date of introduction of substitution therapy with dopaminergic drugs or dopamine agonists
Time period between the date of diagnosis and the date of introduction of dopaminergic substitute therapy or dopaminergic agonists
Evolution of this prescription of substitution therapy over the duration of study
Follow up of dosage of dopaminergic substitute therapy or dopaminergic agonists
Assessment in both groups of the time it takes for the onset of different motor symptoms (including tremor, akinesia and stiffness, speech, walking and balance disorders) and not motor symptoms of Parkinson's disease in relation to initial diagnosis.
Time period between the date of diagnosis and the date of onset of different motor and non-motor symptoms objectified by an increase in item scores specific to these symptoms on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS scale) passed into OFF drug [0-100% : higher scores mean worse outcome]
Evolution of the quality of life of patients in both groups
Parkinson Disease Quotation (PDQ-39) quiz score [0-4 : higher scores mean worse outcome]
Evolution of walking speed in both patient groups
Right and left foot speed measured during a walking task on the Vicon platform without and with dopaminergic treatment
Evolution of walking parameters in both patient groups
Score in the "freezing of gait" questionnaire [0-24 : higher scores mean worse outcome] without and with dopaminergic treatment

Full Information

First Posted
January 27, 2020
Last Updated
March 30, 2023
Sponsor
University Hospital, Grenoble
Collaborators
Commissariat A L'energie Atomique
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1. Study Identification

Unique Protocol Identification Number
NCT04261569
Brief Title
Clinical Trial for Near Infrared Endoventricular Illumination for Neuroprotection in Very Early Cases of Parkinson's Disease (Ev-NIRT)
Acronym
Ev-NIRT
Official Title
Clinical Trial for Near Infrared Endoventricular Illumination for Neuroprotection in Very Early Cases of Parkinson's Disease (Ev-NIRT)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 14, 2020 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
April 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Grenoble
Collaborators
Commissariat A L'energie Atomique

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Parkinson's disease has only pharmacological (essentially dopaminergic) and surgical treatment (essentially high-frequency deep brain stimulation), that are symptomatically effective. none of them is curative, and has the ability to slow down the disease and to protect dopaminergic neurons from death by neurodegeneration. Experimental results, based on preclinical studies, suggest that brain illumination in the Near-InfraRed (NIR) range is likely to slow down this neurodegenerative process. Thus, a medical device system (called Ev-NIRT) has been developed for 670 nm intracerebral illumination of the substantia nigra pars compacta (SNpc), and is planned to be tested for the treatment of Parkinson's disease. In this pilot study the investigators will evaluate the feasibility and tolerance of surgery and brain illumination thanks to the Ev-NIRT medical device, in a group of 7 de novo Parkinson's patients implanted with the innovative medical device. Patients will be monitored for 4 years.
Detailed Description
The level of neuroprotection induced by illumination at 670nm appears effective in preclinical studies, and justify the transfer into a clinical trial. The investigators currently have developed and produced implantable devices, to be implanted into the brain through a minimally invasive endoventricular route. The electrical energy required is supplied by the batteries adapted from those used for deep brain stimulation. The feasibility of trans ventricular implantation is ensured by the experience gained by our team in the endoventricular stimulation of the posterior hypothalamus in the cluster headache. In this clinical study, the investigators will evaluate the tolerance and safety of intraventricular surgical technic and illumination by the Ev-NIRT medical device implanted into the brain of 7 patients with Parkinson's disease. idiopathic, aged 25-65 years, at a very early stage (less than 2 years of evolution). The NIR illumination will begin immediately after surgery. The investigators will also evaluate secondarily, the neuroprotective effect of this new treatment modality, by comparing the decrease of dopaminergic neurons by Positron Emission Tomography (PET)-scan using [11C]PE2I) tracer of implanted patients to that of a control group of 7 patients whose characteristics in terms of duration of evolution and clinical severity are identical, but who are not implanted, and therefore not exposed to NIR illumination. The PET-scan-PE2I exam is conducted in both groups annually for 4 years (a total of 5 measurements) and compared to the PE2I PET obtained at the beginning of participation in the study. A group-wide comparison will be made between the NIR group and the control group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Very Early Stage of Parkinson's Disease
Keywords
Parkinson's disease (PD), Intraventricular illumination by near-infrared light (Ev-NIRT), Positron Emission Tomography (PET), Substantia Nigra Pars Compacta (SNpc), Photobiomodulation, Medical Device (MD)

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
One control arm : patients without any medical device One illuminated arm : patients with intraventricular near-infrared light illumination
Masking
None (Open Label)
Allocation
Randomized
Enrollment
14 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Illuminated arm
Arm Type
Experimental
Arm Description
patients with intraventricular near-infrared light illumination
Arm Title
control arm
Arm Type
No Intervention
Arm Description
patients without any medical device
Intervention Type
Device
Intervention Name(s)
Ev-NIRT
Intervention Description
Endoventricular near infra red treatment : Intraventricular pulsed, chronic, cyclic, near-infrared illumination of the Central Nervous System (CNS) at 150 Hz, 15 mW, 1 minute ON and 5 minutes OFF
Primary Outcome Measure Information:
Title
Incidence of Ev-NIRT Treatment on Emergent Adverse Events (Tolerance) after surgical intervention and NIR illumination following the implantation of the Ev-NIRT medical device
Description
Emergent Adverse Events [Safety and Tolerability]
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Characterization of annual neuronal loss observed by decrease in tracer fixation at the striatum level
Description
Annual measurement of dopaminergic denervation in Positron Emission Tomography (PET) using [11C]PE2I tracer fixation at the striatum level in percentage compared to the white matter fixation of the cerebellum
Time Frame
4 years
Title
Evaluation of the motor clinical signs progression
Description
Scores on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS scale sections II, III and IV) [0-100% : higher scores mean worse outcome]
Time Frame
4 years
Title
Evaluation of the non-motor bahavioral signs progression
Description
Scores on the non-motor scales Behavioral Evaluation in Parkinson's disease (ECMP) [0-4 : higher scores mean worse outcome]
Time Frame
4 years
Title
Evaluation of the non-motor clinical signs progression
Description
Scores on the non-motor scales Lille Apathy Rating Scale (LARS) [-4/+4 : higher scores mean worse outcome]
Time Frame
4 years
Title
Evaluation of depression signs progression
Description
Scores on the non-motor scales Beck Depression Inventory (BDI-II) [0-3 : higher scores mean worse outcome]
Time Frame
4 years
Title
Evaluation of the non-motor symptoms signs progression
Description
Scores on the non-motor scales Non Motor Symptoms scale (NMS) [0-30 : higher scores mean better outcome]
Time Frame
4 years
Title
Comparison between the date of diagnosis and the date of introduction of substitution therapy with dopaminergic drugs or dopamine agonists
Description
Time period between the date of diagnosis and the date of introduction of dopaminergic substitute therapy or dopaminergic agonists
Time Frame
4 years
Title
Evolution of this prescription of substitution therapy over the duration of study
Description
Follow up of dosage of dopaminergic substitute therapy or dopaminergic agonists
Time Frame
4 years
Title
Assessment in both groups of the time it takes for the onset of different motor symptoms (including tremor, akinesia and stiffness, speech, walking and balance disorders) and not motor symptoms of Parkinson's disease in relation to initial diagnosis.
Description
Time period between the date of diagnosis and the date of onset of different motor and non-motor symptoms objectified by an increase in item scores specific to these symptoms on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS scale) passed into OFF drug [0-100% : higher scores mean worse outcome]
Time Frame
4 years
Title
Evolution of the quality of life of patients in both groups
Description
Parkinson Disease Quotation (PDQ-39) quiz score [0-4 : higher scores mean worse outcome]
Time Frame
4 years
Title
Evolution of walking speed in both patient groups
Description
Right and left foot speed measured during a walking task on the Vicon platform without and with dopaminergic treatment
Time Frame
4 years
Title
Evolution of walking parameters in both patient groups
Description
Score in the "freezing of gait" questionnaire [0-24 : higher scores mean worse outcome] without and with dopaminergic treatment
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Clinically diagnosed idiopathic Parkinson's disease according to MDS criteria developed by R.B. Postuma (Anang et al, Neurology, 2014) Dopaminergic denervation confirmed in PET [11C]PE2I with a decrease in tracer fixation at the striatum level of at least 30% on average compared to the white matter fixation of the cerebellum Patients willing to start dopaminergic treatment Very early stage of the disease: Diagnosis of recent Parkinson's disease (less than two years after a neurologist's diagnosis) Hoehn and Yahr Stage 1 to 2 Maximum 2 tremor on the MDS-UPDRS scale Naive of any anti-Parkinsonian treatment Between 25 and 65 years of age Score on Beck Depression Inventory (BDI) scale below the value of 20 Easy handling of the French language in oral and written language Social security affiliates or beneficiaries of such a scheme Informed and written consent signed by the patient Exclusion Criteria: All categories of protected persons: pregnant woman, parturient, breastfeeding mother, person deprived of liberty by judicial or administrative decision, person subject to a measure of legal protection, hospitalized for psychiatric disorder Carcinological history in the previous 5 years, not stabilized Uncontrolled medical condition that may lead to complications Preoperative brain Magnetic Resonance Imaging (MRI) showing brain damage that may be responsible for Parkinson's syndrome or a significant surgical risk (e.g. vascular malformation) Surgical or anesthetic contraindication History of brain infection with herpes virus Contraindication to MRI (claustrophobia, non-compatible mri metal prosthesis, etc.) Predictable need for frequent use of MRI scans after surgery Unstabilized psychotropic treatment Patient with cognitive impairment at the outset of illness (Montreal Cognitive Assessment (MoCA) score - 26) Atypias suspecting atypical Parkinson's syndrome Chronic treatment with L-Dopa or dopamine agonist Presence of another serious pathology (major depressive episode, suicidal patient, active psychosis ...) Participation in another interventional clinical trial Wearing pace makers other than brain
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cécile MORO, PhD
Phone
33 (0)4 38 78 06 11
Email
cecile.moro@cea.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline SANDRE-BALLESTER, PhD
Phone
33 (0)4 38 78 28 51
Email
CSandreballester@chu-grenoble.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephan CHABARDES, MD, PhD
Organizational Affiliation
University Hospital, Grenoble
Official's Role
Principal Investigator
Facility Information:
Facility Name
CLINATEC
City
Grenoble
ZIP/Postal Code
38000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cécile MORO, PhD
Phone
33 (0)4 38 78 06 11
Email
cecile.moro@cea.fr
First Name & Middle Initial & Last Name & Degree
Caroline SANDRE-BALLESTER, PhD
Phone
33 (0)4 38 78 28 51
Email
CSandreballester@chu-grenoble.fr
First Name & Middle Initial & Last Name & Degree
Stephan CHABARDES, MD, PhD

12. IPD Sharing Statement

Citations:
PubMed Identifier
27244468
Citation
Chabardes S, Carron R, Seigneuret E, Torres N, Goetz L, Krainik A, Piallat B, Pham P, David O, Giraud P, Benabid AL. Endoventricular Deep Brain Stimulation of the Third Ventricle: Proof of Concept and Application to Cluster Headache. Neurosurgery. 2016 Dec;79(6):806-815. doi: 10.1227/NEU.0000000000001260.
Results Reference
background
PubMed Identifier
26456231
Citation
Darlot F, Moro C, El Massri N, Chabrol C, Johnstone DM, Reinhart F, Agay D, Torres N, Bekha D, Auboiroux V, Costecalde T, Peoples CL, Anastascio HD, Shaw VE, Stone J, Mitrofanis J, Benabid AL. Near-infrared light is neuroprotective in a monkey model of Parkinson disease. Ann Neurol. 2016 Jan;79(1):59-75. doi: 10.1002/ana.24542. Epub 2015 Dec 12.
Results Reference
background
PubMed Identifier
27396907
Citation
Moro C, El Massri N, Darlot F, Torres N, Chabrol C, Agay D, Auboiroux V, Johnstone DM, Stone J, Mitrofanis J, Benabid AL. Effects of a higher dose of near-infrared light on clinical signs and neuroprotection in a monkey model of Parkinson's disease. Brain Res. 2016 Oct 1;1648(Pt A):19-26. doi: 10.1016/j.brainres.2016.07.005. Epub 2016 Jul 7.
Results Reference
background
PubMed Identifier
26613166
Citation
Reinhart F, Massri NE, Chabrol C, Cretallaz C, Johnstone DM, Torres N, Darlot F, Costecalde T, Stone J, Mitrofanis J, Benabid AL, Moro C. Intracranial application of near-infrared light in a hemi-parkinsonian rat model: the impact on behavior and cell survival. J Neurosurg. 2016 Jun;124(6):1829-41. doi: 10.3171/2015.5.JNS15735. Epub 2015 Nov 27.
Results Reference
background
PubMed Identifier
26793049
Citation
Johnstone DM, Moro C, Stone J, Benabid AL, Mitrofanis J. Turning On Lights to Stop Neurodegeneration: The Potential of Near Infrared Light Therapy in Alzheimer's and Parkinson's Disease. Front Neurosci. 2016 Jan 11;9:500. doi: 10.3389/fnins.2015.00500. eCollection 2015.
Results Reference
background

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Clinical Trial for Near Infrared Endoventricular Illumination for Neuroprotection in Very Early Cases of Parkinson's Disease (Ev-NIRT)

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