Intracerebroventricular anaerobic dopamine in Parkinson’s disease with l-dopa-related complications: a phase 1/2 randomized-controlled trial
Caroline Moreau, Pascal Odou, Julien Labreuche, Alexandre Demailly, Gustavo Touzet, Nicolas Reyns, Bastien Gouges, Alain Duhamel, Christine Barthélémy, Damien Lannoy, Natacha Carta, Benjamin Palas, Michèle Vasseur, Felix Marchand, Thomas Ollivier, Céline Leclercq, Camille Potey, Thavarak Ouk, Simon Baigne, Kathy Dujardin, Louise Carton, Anne‐Sophie Rolland, Jean Christophe Devedjian, Véronique Foutel, Dominique Deplanque, Matthieu Fisichella, David Devos
Abstract
Continuous compensation for cerebral dopamine deficiency represents an ideal treatment for Parkinson's disease. Dopamine does not cross the digestive and blood-brain barriers and is rapidly oxidized. The new concept is the intracerebroventricular administration of anaerobic dopamine (A-dopamine) using an abdominal pump connected to a subcutaneous catheter implanted in the third ventricle, near the striatum. An open-label phase 1 study showed no serious adverse reactions induced by A-dopamine in 12 patients. A randomized, controlled, open-label, crossover phase 2 study of 1 month of A-dopamine versus 1 month of optimized oral antiparkinsonian therapy was conducted in 9 patients. The primary endpoint, a blinded assessment of the percentage over target (that is, time with dyskinesia or bradykinesia), recorded by home actimetry using a wristwatch, was significantly reduced on A-dopamine compared with that on oral treatment alone (P = 0.027), with a median within-patient difference of -10.4 (Hedge g = -0.62 (95% confidence interval: -1.43, -0.08)). Home diaries were also significantly improved. These initial data on the feasibility, safety and effects of this new device-assisted therapy suggest validation by a large randomized double-blind trial. ClinicalTrials.gov registration: NCT04332276 .