Safety and efficacy of subcutaneous night-time only apomorphine infusion to treat insomnia in patients with Parkinson's disease (APOMORPHEE): a multicentre, randomised, controlled, double-blind crossover study

Cock, Valérie Cochen De; Dodet, Pauline; Leu‐Semenescu, Smaranda; Aerts, Cécile; Castelnovo, Giovanni; Abril, Beatriz; Drapier, Sophie; Olivet, Hélène; Corbillé, Anne‐Gaëlle; Leclair‐Visonneau, Laurène; Sallansonnet-Froment, M.; Lebouteux, M.; Anheim, Mathieu; Ruppert, Élisabeth; Vitello, Nicolas; Eusebio, Alexandre; Lambert, Isabelle; Marqués, Ana; Fantini, María Livia; Devos, David; Monaca, Christelle; Benard-Serre, Nicolas; Lacombe, Sandy; Vidailhet, Marie; Arnulf, Isabelle; Doulazmi, Mohamed; Roze, Emmanuel

doi:10.1016/s1474-4422(22)00085-0

Cited by 39 publications

(33 citation statements)

References 34 publications

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“…54,55 Over 90% of PD patients report various sleep problems, including insomnia, excessive daytime sleepiness, RBD, and circadian abnormalities. 56 As the disease progresses, disturbances in sleep become increasingly frequent and severe. [57][58][59][60] Sleep-related symptoms have a significant impact on PD-related disabilities, compared with motor symptoms.…”

Section: Discussionmentioning

confidence: 99%

Reduced coupling of global brain function and cerebrospinal fluid dynamics in Parkinson’s disease

Wang

Song

Zhou

et al. 2023

J Cereb Blood Flow Metab

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Dysfunction of the glymphatic system, an intracranial clearance pathway that drains misfolded proteins, has been implicated in the onset of Parkinson’s disease (PD). Recently, the coupling strength of global blood-oxygen-level-dependent (gBOLD) signals and cerebrospinal fluid (CSF) inflow dynamics have been suggested to be an indicator of glymphatic function. Using resting-state functional magnetic resonance imaging (MRI), we quantified gBOLD–CSF coupling strength as the cross-correlation between baseline gBOLD and CSF inflow signals to evaluate glymphatic function and its association with the clinical manifestations of PD. We found that gBOLD–CSF coupling in drug-naïve PD patients was significantly weaker than that in normal controls, but significantly stronger in patients less affected by sleep disturbances than in those more affected by sleep disturbances, based on the PD sleep scale. Furthermore, we collected longitudinal data from patients and found that baseline gBOLD–CSF coupling negatively correlated with the rate of change over time, but positively correlated with the rate of change in UPDRS-III scores. In conclusion, severe gBOLD–CSF decoupling in PD patients may reflect longitudinal motor impairment, thereby providing a potential marker of glymphatic dysfunction in PD.

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Section: Discussionmentioning

confidence: 99%

Reduced coupling of global brain function and cerebrospinal fluid dynamics in Parkinson’s disease

Wang

Song

Zhou

et al. 2023

J Cereb Blood Flow Metab

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“…Several factors can influence its subcutaneous absorption and consequently its efficacy: injection site, state of the skin, volume and depth of injection and the presence of subcutaneous nodules [ 116 ]. A recent study highlighted its possible role in improving sleep disturbance when used only as a night-time perfusion among patients with PD with motor complications and insomnia [ 117 ].…”

Section: Surgical and Device-aided Therapiesmentioning

confidence: 99%

Off-time Treatment Options for Parkinson’s Disease

2023

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Motor fluctuations (MF) are deemed by patients with Parkinson's disease (PD) as the most troublesome disease feature resulting from the increasing impairment in responsiveness to dopaminergic drug treatments. MF are characterized by the loss of a stable response to levodopa over the nychthemeron with the reappearance of motor (and non-motor) parkinsonian clinical signs at various moments during the day and night. They normally appear after a few years of levodopa treatment and with a variable, though overall increasing severity, over the disease course. The armamentarium of first-line treatment options has widened in the last decade with new once-a-daily compounds,

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“…No direct comparisons of device-aided therapies with off-time or QoL as the main endpoints were identified in the last 3 years (a comparison of LCIG and DBS on QoL outcomes is ongoing [ 66 ]). Likewise, recently published RCTs of individual device-aided therapies have focused on different aspects of treatment such as dyskinesia [ 67 ], night-time treatment and sleep disturbances [ 68 ], and management of axial features [ 69 ]. A host of single-arm and/or observational studies on these three device-aided therapies have been published and some report off-time or QoL as the main outcomes [ 70 – 76 ]; however, the results of these studies would have no clear impact on the current analysis.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson’s Disease: A Systematic Review and Bayesian Network Meta-analysis

et al. 2022

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Introduction Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson’s disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD. Methods A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson’s Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson’s Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness. Results A total of 22 studies fulfilled the inclusion criteria ( n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5–70.9 years, duration of PD was 9.1–15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT ( p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL. Conclusions This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s40263-022-00963-9.

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Safety and efficacy of subcutaneous night-time only apomorphine infusion to treat insomnia in patients with Parkinson's disease (APOMORPHEE): a multicentre, randomised, controlled, double-blind crossover study

Cited by 39 publications

References 34 publications

Reduced coupling of global brain function and cerebrospinal fluid dynamics in Parkinson’s disease

Reduced coupling of global brain function and cerebrospinal fluid dynamics in Parkinson’s disease

Off-time Treatment Options for Parkinson’s Disease

Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson’s Disease: A Systematic Review and Bayesian Network Meta-analysis

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