Dopaminergic restauratIon by intraVEntriculaire Administration

NCT04332276 | Completed Phase 1 DMC

• 2 other identifiers: 2018_492020-000155-12
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective monocentric randomized controlled open-label proof-of-concept study in cross-over of two 1-month periods and a long-term follow-up period not to exceed September 30, 2023, with 2 groups: Intracerebroventricular A-dopamine versus optimized oral medical treatment in parkinsonian patients at the stage of severe motor complications (fluctuations and dyskinesias) related to oral L-dopa. 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.

Conditions

Parkinson Disease

Keywords

Parkinson's disease; dopamine; L-dopa related motor complications; dyskinesia; symptomatic treatment; disease modifying effect

Outcome Measures

Primary Outcomes (2)

• Percent Time Over Target

  This is the amount of time that the BKS was over target and is a representation of "OFF" time in the period from 09:00-18:00 and is the proportion of time that a subject's BKS is greater than the target used in this study (BKS=26). The PTO does not include periods of immobility.

  Month 1 through Month 2

• The number of hours with either perfect control or with a slight slowdown on the 7-day schedule

  Primary endpoint of the long-term follow-up phase . This will be compared to that obtained in phase 2 to demonstrate the maintenance of long-term efficacy control.

  follow up visits every 6 months until the deadline of September 30, 2023

Secondary Outcomes (18)

• bradykinesia score

  At baseline and during the last day of each month of assessment ( an average 4 months)

• dyskinesia score

  At baseline and during the last day of each month of assessment ( an average 4 months)

• The Percent Time Immobile

  At baseline and during the last day of each month of assessment ( an average 4 months)

• The Fluctuation Dyskinesia Score

  At baseline and during the last day of each month of assessment ( an average 4 months)

• The Percent Time Tremor

  At baseline and during the last day of each month of assessment ( an average 4 months)

Study Arms (2)

Cerebroventricular administration of A- dopamine

EXPERIMENTAL

Cerebroventricular administration of dopamine prepared and stored in anaerobia

Drug: A-dopamine

Optimized oral dopaminergic treatment

ACTIVE COMPARATOR

Optimized oral dopaminergic treatment with L-dopa (at least 5 doses a day) with dopaminergic agonist, monoamine B inhibitor and catechol-o-methyl inhibitor (if tolerated) (A-dopamine replaced by saline un the pump during optimized oral dopaminergic treatment)

Drug: optimized oral treatment

Interventions

A-dopamine DRUG

During the phase 1 (titration), it is planned to increase dopamine by maximum 0.25 mg per hour over the daytime period, which corresponds to a maximum increase of 4.5 mg per day (based on the 18 hours of the daytime period, since nocturnal needs are much less important). Then, depending on tolerance and efficacy, conservative titration will be continued for a target dose of 30-87 mg per day. During the phase 2 (efficacy), the treatment will be maintained at the minimum effective dose, planned between 30 and 87 mg per day, for 30 days.

Cerebroventricular administration of A- dopamine

optimized oral treatment DRUG

The patient will received his usual dopaminergic treatment.

Optimized oral dopaminergic treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parkinson\'s disease at the stage of L-dopa-induced severe motor and non-motor complications
• Men or women over 18 years old
• Parkinson\'s disease according to MDS criteria
• Severe motor complications including motor fluctuations with at least 2 hours of Off and 1 hour of dyskinesias uncontrolled by optimized oral drug therapy, i.e. with at least 5 doses of L-dopa and the addition or trial of a dopaminergic agonist (if tolerated) per os or by apomorphine pump
• The patient meets the criteria for a second-line invasive treatment such as deep brain stimulation (subthalamic or medial pallidum) or intrajejunal administration of levodopa gel (Duodopa®).
• Patients with a contraindication or who prefer this invasive therapeutic alternative to the other two existing and validated therapies (subthalamic stimulation or Duodopa®) because of its advantages: lower theoretical risk of intracerebroventricular delivery compared to subthalamic stimulation and better ergonomics than Duodopa®, but with the disadvantage of an as yet unproven benefit.
• Social security
• Able to provide free and informed consent to participate in research
• Patient willing to comply with all study procedures and duration
• Patient not planning to change lifestyle (nutritionally, physically or socially) during study participation

You may not qualify if:

• Over 75 years of age
• Subjects not receiving at least 5 doses per day of oral dopaminergic therapy
• Subject without a prior trial of an apomorphine pump (of lower risk); apomorphine pump treatment being a failure or a contraindication or refused by the patient
• Patient with parkinsonian dementia (DSM IV and MDS criteria and MOCA score \< or equal to 22)
• Isolated patient, defined as the absence of a caregiver present at least 3 hours/day in the patient\'s home.
• History of a fall in the last 6 months and/or a score \>1 on items 2.12 (Walking and balance) and/or 3.12 (Postural stability) of the MDS-UPDRS scale
• Presence of another serious pathology threatening short- or medium-term vital prognosis, malnourished or cachectic patient.
• Hemostasis disorders
• Cardiac rhythm disorders and/or heart failure not controlled by treatment
• Uncontrolled blood pressure release
• Breastfeeding and pregnancy
• Women of childbearing age without effective contraception
• Contraindication to general anaesthesia
• Taking treatments containing guanethidine or related compounds or non-selective and selective monoamine oxidase A inhibitors (iproniazid, moclobemide, toloxatone)
• Neurosurgical contraindication (severe cerebral atrophy, brain tumor, infarction or other cerebral pathology, CSF flow disorder)

Sponsors & Collaborators

• University Hospital, Lille: lead
• InBrain Pharma: collaborator

Study Sites (1)

Hopital Roger Salengro, CHU Lille

Lille, 59037, France

Location

Related Publications (1)

• Moreau C, Odou P, Labreuche J, Demailly A, Touzet G, Reyns N, Gouges B, Duhamel A, Barthelemy C, Lannoy D, Carta N, Palas B, Vasseur M, Marchand F, Ollivier T, Leclercq C, Potey C, Ouk T, Baigne S, Dujardin K, Carton L, Rolland AS, Devedjian JC, Foutel V, Deplanque D, Fisichella M, Devos D. Intracerebroventricular anaerobic dopamine in Parkinson's disease with L-dopa-related complications: a phase 1/2 randomized-controlled trial. Nat Med. 2025 Mar;31(3):819-828. doi: 10.1038/s41591-024-03428-2. Epub 2025 Jan 7.

  PMID: 39775041 RESULT

MeSH Terms

Conditions

Parkinson Disease; Dyskinesias

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Caroline Moreau, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

• David DEVOS, MD, PhD

  University Hospital, Lille

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2020
• First Posted: April 2, 2020
• Study Start: September 18, 2020
• Primary Completion: May 6, 2024
• Study Completion: May 6, 2024
• Last Updated: May 14, 2026

Record last verified: 2022-10

Locations

FR (1)