Trial of Lixisenatide in Early Parkinson's Disease.

BACKGROUND: Lixisenatide, a glucagon-like peptide-1 receptor agonist used for the treatment of diabetes, has shown neuroprotective properties in a mouse model of Parkinson's disease. METHODS: In this phase 2, double-blind, randomized, placebo-controlled trial, we assessed the effect of lixisenatide on the progression of motor disability in persons with Parkinson's disease. Participants in whom Parkinson's disease was diagnosed less than 3 years earlier, who were receiving a stable dose of medications to treat symptoms, and who did not have motor complications were randomly assigned in a 1:1 ratio to daily subcutaneous lixisenatide or placebo for 12 months, followed by a 2-month washout period. The primary end point was the change from baseline in scores on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (range, 0 to 132, with higher scores indicating greater motor disability), which was assessed in patients in the on-medication state at 12 months. Secondary end points included other MDS-UPDRS subscores at 6, 12, and 14 months and doses of levodopa equivalent. RESULTS: A total of 156 persons were enrolled, with 78 assigned to each group. MDS-UPDRS part III scores at baseline were approximately 15 in both groups. At 12 months, scores on the MDS-UPDRS part III had changed by -0.04 points (indicating improvement) in the lixisenatide group and 3.04 points (indicating worsening disability) in the placebo group (difference, 3.08; 95% confidence interval, 0.86 to 5.30; P = 0.007). At 14 months, after a 2-month washout period, the mean MDS-UPDRS motor scores in the off-medication state were 17.7 (95% CI, 15.7 to 19.7) with lixisenatide and 20.6 (95% CI, 18.5 to 22.8) with placebo. Other results relative to the secondary end points did not differ substantially between the groups. Nausea occurred in 46% of participants receiving lixisenatide, and vomiting occurred in 13%. CONCLUSIONS: In participants with early Parkinson's disease, lixisenatide therapy resulted in less progression of motor disability than placebo at 12 months in a phase 2 trial but was associated with gastrointestinal side effects. Longer and larger trials are needed to determine the effects and safety of lixisenatide in persons with Parkinson's disease. (Funded by the French Ministry of Health and others; LIXIPARK ClinicalTrials.gov number, NCT03439943.).

Oxycodone or Higher Dose of Levodopa for the Treatment of Parkinsonian Central Pain: OXYDOPA Trial.

BACKGROUND: Among the different types of pain related to Parkinson's disease (PD), parkinsonian central pain (PCP) is the most disabling. OBJECTIVES: We investigated the analgesic efficacy of two therapeutic strategies (opioid with oxycodone- prolonged-release (PR) and higher dose of levodopa/benserazide) compared with placebo in patients with PCP. METHODS: OXYDOPA was a randomized, double-blind, double-dummy, placebo-controlled, multicenter parallel-group trial run at 15 centers within the French NS-Park network. PD patients with PCP (≥30 on the Visual Analogue Scale [VAS]) were randomly assigned to receive oxycodone-PR (up to 40 mg/day), levodopa/benserazide (up to 200 mg/day) or matching placebo three times a day (tid) for 8 weeks at a stable dose, in add-on to their current dopaminergic therapy. The primary endpoint was the change in average pain intensity over the previous week rated on VAS from baseline to week-10 based on modified intention-to-treat analyses. RESULTS: Between May 2016 and August 2020, 66 patients were randomized to oxycodone-PR (n = 23), levodopa/benserazide (n = 20) or placebo (n = 23). The mean change in pain intensity was -17 ± 18.5 on oxycodone-PR, -8.3 ± 11.1 on levodopa/benserazide, and -14.3 ± 18.9 in the placebo groups. The absolute difference versus placebo was -1.54 (97.5% confidence interval [CI], -17.0 to 13.90; P = 0.8) on oxycodone-PR and +7.79 (97.5% CI, -4.99 to 20.58; P = 0.2) on levodopa/benserazide. Similar proportions of patients in each group experienced all-cause adverse events. Those leading to study discontinuation were most frequently observed with oxycodone-PR (39%) than levodopa/benserazide (5%) or placebo (15%). CONCLUSIONS: The present trial failed to demonstrate the superiority of oxycodone-PR or a higher dose of levodopa in patients with PCP, while oxycodone-PR was poorly tolerated. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

[Current issues surrounding Parkinson's disease]. / Enjeux actuels autour de la maladie de Parkinson.

The number of people suffering from Parkinson's disease is constantly increasing. Diagnosis is based on the motor and non-motor symptoms present throughout the course of the disease. To preserve patient autonomy, the main therapeutic challenge is to propose a treatment adapted to each profile, in conjunction with the implementation of non-medication strategies, reflection on improved accessibility to existing medication and research into innovative therapies.