Dopaminergic restauratIon by intraVEntriculaire Administration

• Status: Recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

A proof of concept study phase I/IIb with a first phase I of one month of slow titration to demonstrate the feasibility and the safety and then a phase IIb using a single blind randomized cross over study (2 periods of 1 month) to demonstrate that cerebroventricular administration of A-dopamine (dopamine prepared in anaerobia to avoid dopamine oxidation) affords a better control of motor fluctuations including dyskinesia as compared with optimized oral treatment in patients with PD at the stage of severe motor complications related with oral L-dopa using continuous actimetry at home.

In this study it will be expected to: 1) a higher benefit on motor symptoms 2) without tachyphylaxis, 3) a good ergonomic of the intra-abdominal pump refilled with A-dopamine every two weeks as compared with the numerous daily L-dopa doses and 4) a good safety profile of this classical neurosurgical procedure.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Lille
• Collaborator: InBrain Pharma
• Treatments: Dopamine; Dopamine Agonists

Criteria

Inclusion Criteria:

• Parkinson's disease in the stage of severe motor and non-motor complications related to L dopa

• Parkinson's disease according to MDS criteria

• Severe motor fluctuations with at least 2 hours of Off period and/or 1 hour of dyskinesia despite an optimized oral dopaminergic treatment with at least 5 daily doses of oral L-dopa and a dopaminergic agonist (daily taken or at least tried: oral, subcutaneous patch, apomorphine pump)

• Patient who met criteria for a second-line invasive treatment such as deep brain stimulation (subthalamic or internal pallidum) or intrajunal administration of levodopa gel (Duodopa®)

• Patient with a contraindication or who preferred the DIVE strategy as compared with the two other invasive treatments (subthalamic nucleus stimulation Duodopa®) because of the following advantages: lower neurosurgical risk than bilateral deep brain implantation of electrodes and a better ergonomic than Duodopa® but knowing that the benefits of DIVE are not yet demonstrated.

• Affiliate or beneficiary of a social security scheme

• Subject having signed informed consent

• Patient willing to comply with all procedures of the study and its duration

• No planned changes in lifestyle (nutritional and physical, social interactions) during the life of the protocol

Exclusion Criteria:

• Patients aged over 75 years

• Patients with severe other chronic neurological or mental pathology

• Patients without at least 5 doses of L-dopa per day and/or with less than 2 hours of Off period and/or 1 hour of dyskinesia

• Patients with no try of apomorphine pump

• Subjects with a previous psychiatric history (based on the semi-structured psychiatric interview with the MINI of DSM V) : severe depression, severe generalized anxiety, suicidal tendencies, psychotic symptoms, severe mood disorders, mania, schizophrenia. Dysthymia and an isolated history of depression or moderate anxiety do not constitute an exclusion criterion.

• Patients with dementia according to the MDS criteria and MOCA score ≤ 22.

• Patients with severe other pathology that could impact the survival at short- or medium-term, malnourished patients, cachexia

• Patients with contra indication to general anesthesia

• Taking treatments containing guanethidine or its relatives, or non-selective and selective monoamine oxidase A inhibitors (iproniazid, moclobemide, toloxatone)

• Patients with contra indication to neurosurgery (severe cerebral atrophy, brain tumor, severe infractus, ventricular pathology or other brain pathology) that can interfere with ventricular access.

• Contraindication to the abdominal placement of a pump and a subcutaneous catheter altering the healing and the transcutaneous filling (ex: major obesity, skin pathology,...)

• Contraindication to the realization of an MRI (pace maker, claustrophobia...). In case of allergy or intolerance to gadolinium, the latter will not be injected during the preoperative MRI

• Contraindication to DaTscan and/or F-dopa PET (for the first 5 patients included)

• Patients with active infectious disease

• Patient with hemostasis disorders

• Patient with uncontrolled cardiac diseases and uncontrolled arterial hypertension

• Patients with congenital or acquired immune deficiency that could favor infection

• Subject during breastfeeding or pregnancy

• Patient under guardianship or curatorship

• Patient already participating in another therapeutic trial with the use of an investigational drug or in a period of exclusion period