Very Early Stage of Parkinson's Disease Clinical Trial
— Ev-NIRTOfficial title:
Clinical Trial for Near Infrared Endoventricular Illumination for Neuroprotection in Very Early Cases of Parkinson's Disease (Ev-NIRT)
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.
| Status | Recruiting |
| Enrollment | 14 |
| Est. completion date | April 2028 |
| Est. primary completion date | January 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 25 Years to 65 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| France | CLINATEC | Grenoble |
| Lead Sponsor | Collaborator |
|---|---|
| University Hospital, Grenoble | Commissariat A L'energie Atomique |
France,
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. — View 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. — View 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. — View 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. — View 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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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] | 4 years | |
| Secondary | 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 | 4 years | |
| Secondary | 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] | 4 years | |
| Secondary | 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] | 4 years | |
| Secondary | 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] | 4 years | |
| Secondary | Evaluation of depression signs progression | Scores on the non-motor scales Beck Depression Inventory (BDI-II) [0-3 : higher scores mean worse outcome] | 4 years | |
| Secondary | 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] | 4 years | |
| Secondary | 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 | 4 years | |
| Secondary | Evolution of this prescription of substitution therapy over the duration of study | Follow up of dosage of dopaminergic substitute therapy or dopaminergic agonists | 4 years | |
| Secondary | 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] | 4 years | |
| Secondary | 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] | 4 years | |
| Secondary | 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 | 4 years | |
| Secondary | 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 | 4 years |