Parkinson's Kinetigraph in the Selection of Levodopa-Carbidopa Intestinal Gel for Motor Fluctuations Refractory to Deep Brain Stimulation.
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SUBMITTER: Noui Y
PROVIDER: S-EPMC8490188 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7396832 | biostudies-literature
Project description:ObjectiveTo evaluate the effectiveness of levodopa-carbidopa intestinal gel (LCIG) as an add-on rescue therapy following deep brain stimulation (DBS) for treatment of motor fluctuations.BackgroundBoth DBS and LCIG are FDA-approved therapies for treatment of motor fluctuations in advanced PD. Few studies have examined dual therapy for refractory motor fluctuations and it is unknown what the effect on quality of life will be in advanced PD.MethodsWe conducted a retrospective study using a large database of all medical and surgical PD cases at the University of Florida. Six patients were identified with DBS who subsequently received rescue LCIG therapy. The clinical histories, indications for intervention and outcomes were reviewed.ResultsAll patients were managed initially with DBS (bilateral STN DBS (n = 3), bilateral GPi DBS (n = 1), unilateral GPI DBS (n = 2)). Patients with well-placed (n = 3) and suboptimally placed DBS leads (n = 3) had significant reduction in their motor fluctuations with improvement in the off-medication time after rescue LCIG therapy. Improvement in quality of life scores (PDQ-39) was appreciated in four DBS patients following the addition of LCIG therapy.ConclusionsLCIG is a promising add-on rescue therapy for select patients with existing DBS devices. The LCIG may possibly reduce motor fluctuations and improve quality of life in advanced PD irrespective of the DBS target or the accuracy of lead placement. Dual therapy may also be ideal for patients who are considered high risk for additional DBS surgeries.
| S-EPMC6801178 | biostudies-literature
Project description:BackgroundLevodopa-carbidopa intestinal gel (LCIG; carbidopa-levodopa enteral suspension in the United States), delivered via percutaneous gastrojejunostomy (PEG-J) and titrated in the inpatient setting, is an established treatment option for advanced Parkinson's disease (PD) patients with motor fluctuations. However, long-term prospective data on the efficacy of LCIG on non-motor symptoms and the safety of outpatient titration are limited.MethodsIn this 60-week, open-label phase 3b study, LCIG titration was initiated in an outpatient setting following PEG-J placement in PD patients. The efficacy of LCIG on motor and non-motor symptoms, quality of life, and safety was assessed.ResultsThirty-nine patients were enrolled in the study and 28 patients completed the treatment. A majority of patients (54%) completed outpatient titration within the first week of LCIG infusion. LCIG led to significant reductions from baseline in Non-Motor Symptom Scale (NMSS) total score (least squares mean ± SE = -17.6 ± 3.6, P < 0.001) and 6 of the NMSS domain scores (sleep/fatigue, attention/memory, gastrointestinal tract, urinary, sexual function, miscellaneous) at week 12. These reductions were maintained at week 60 with the exception of the urinary domain. "Off" time (-4.9 ± 0.5 hours/day, P < 0.001) and "On" time without troublesome dyskinesia (-4.3 ± 0.6 hours/day, P < 0.001) were improved at week 60. Adverse events (AEs) were reported in 37 (95%) patients.ConclusionsLCIG treatment led to reductions in non-motor symptom burden and motor fluctuations in advanced PD patients. The safety profile was consistent with previous studies that used inpatient titration and outpatient titration did not appear to pose additional risk.
| S-EPMC5724683 | biostudies-literature
Project description:Background: Currently, some advanced treatments such as Levodopa-Carbidopa intestinal gel infusion (LCIG), deep-brain stimulation (DBS), and subcutaneous apomorphine infusion have become alternative strategies for advanced Parkinson's disease (PD). However, which treatment is better for individual patients remains unclear. This review aims to compare therapeutic effects of motor and/or non-motor symptoms of advanced PD patients between LCIG and DBS. Methods: We manually searched electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included articles published until April 04, 2019 using related terms, without language restriction. We included case-controlled cohort studies and randomized-controlled trials, which directly compared differences between LCIG and DBS. The Newcastle-Ottawa scale (NOS), proposed by the Cochrane Collaboration, was utilized to assess the quality of the included studies. Two investigators independently extracted data from each trial. Pooled standard-mean differences (SMDs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated by meta-analysis. Outcomes were grouped according to the part III and part IV of the Unified Parkinson Disease Rating Scale (UPDRS) and adverse events. We also descriptively reviewed some data, which were unavailable for statistical analysis. Results: This review included five cohort trials of 257 patients for meta-analysis. There were no significant differences between LCIG and subthalamic nucleus deep-brain stimulation (STN-DBS) on UPDRS-III and adverse events comparisons: UPDRS-III (pooled SMDs = 0.200, 95% CI: -0.126-0.527, P = 0.230), total adverse events (pooled RRs = 1.279, 95% CI: 0.983-1.664, P = 0.067), serious adverse events (pooled RRs = 1.539, 95% CI: 0.664-3.566, P = 0.315). Notably, the improvement of UPDRS-IV was more significant in STN-DBS groups: pooled SMDs = 0.857, 95% CI: 0.130-1.584, P = 0.021. However, the heterogeneity was moderate for UPDRS-IV (I 2 = 73.8%). Conclusion: LCIG has comparable effects to STN-DBS on motor function for advanced PD, with acceptable tolerability. More large, well-designed trials are needed to assess the comparability of LCIG and STN-DBS in the future.
| S-EPMC6718716 | biostudies-literature
Project description:Levodopa-carbidopa intestinal gel (LCIG) delivered continuously via percutaneous endoscopic gastrojejunostomy (PEG-J) tube has been reported, mainly in small open-label studies, to significantly alleviate motor complications in Parkinson's disease (PD). A prospective open-label, 54-week, international study of LCIG is ongoing in advanced PD patients experiencing motor fluctuations despite optimized pharmacologic therapy. Pre-planned interim analyses were conducted on all enrolled patients (n = 192) who had their PEG-J tube inserted at least 12 weeks before data cutoff (July 30, 2010). Outcomes include the 24-h patient diary of motor fluctuations, Unified Parkinson's Disease Rating Scale (UPDRS), Clinical Global Impression-Improvement (CGI-I), Parkinson's Disease Questionnaire (PDQ-39), and safety evaluations. Patients (average PD duration 12.4 yrs) were taking at least one PD medication at baseline. The mean (±SD) exposure to LCIG was 256.7 (±126.0) days. Baseline mean "Off" time was 6.7 h/day. "Off" time was reduced by a mean of 3.9 (±3.2) h/day and "On" time without troublesome dyskinesia was increased by 4.6 (±3.5) h/day at Week 12 compared to baseline. For the 168 patients (87.5%) reporting any adverse event (AE), the most common were abdominal pain (30.7%), complication of device insertion (21.4%), and procedural pain (17.7%). Serious AEs occurred in 60 (31.3%) patients. Twenty-four (12.5%) patients discontinued, including 14 (7.3%) due to AEs. Four (2.1%) patients died (none deemed related to LCIG). Interim results from this advanced PD cohort demonstrate that LCIG produced meaningful clinical improvements. LCIG was generally well-tolerated; however, device and procedural complications, while generally of mild severity, were common.
| S-EPMC3661282 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to assess the effect of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) in advanced Parkinson's disease patients with troublesome dyskinesia.MethodsPost hoc analyses of patient data from a 12-week, randomized, double-blind study and a 54-week open-label study were performed. Efficacy was assessed in the subgroup of patients defined by ?1 hour of "on" time with troublesome dyskinesia at baseline as recorded in Parkinson's disease symptom diaries (double blind: n?=?11 levodopa-carbidopa intestinal gel, n?=?12 oral levodopa-carbidopa; open label: n?=?144 levodopa-carbidopa intestinal gel). The changes in "off" time, "on" time with and without troublesome dyskinesia, and the overall safety and tolerability of levodopa-carbidopa intestinal gel were analyzed.ResultsAlthough not significantly different from oral levodopa treatment (P?>?.05) in the double-blind study, levodopa-carbidopa intestinal gel treatment resulted in a reduction from baseline in "on" time with troublesome dyskinesia (mean [standard deviation] hours: baseline?=?3.1 [1.7], change from baseline to final?=?-1.8 [1.8], P?=?.014), increase in "on" time without troublesome dyskinesia (baseline?=?7.4 [2.2], change?=?4.4 [3.6], P?=?.004), and decrease in "off" time (baseline?=?5.5 [1.3], change?=?-2.7 [2.8], P?=?.015). Similar trends were found in the open-label study. An increase in levodopa-carbidopa intestinal gel dose was not significantly correlated with increased "on" time with troublesome dyskinesia in either study (double blind: r?=?-.073, P?=?.842; open label: r?=?-0.001, P?=?.992). Adverse events were usually mild to moderate in severity and related to the gastrointestinal procedure.ConclusionOur exploratory analyses suggest that optimizing levodopa delivery with levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson's disease.
| S-EPMC5066747 | biostudies-literature
Project description:BackgroundLevodopa-carbidopa intestinal gel (LCIG) treatment has shown variable effect on dyskinesia in Parkinson's disease (PD).ObjectiveTo identify PD patients who are likely to have troublesome dyskinesia under LCIG treatment and describe the pharmacokinetic-dynamic profile and dyskinesia phenomenology of those patients.MethodsPD patients were assessed for clinical and therapeutic variables, before LCIG treatment (T0) and at last outpatient visit (T1). Sub-groups of patients with and without "troublesome dyskinesia" (UPDRS IV, item 33 ≥2), matched for disease and LCIG treatment duration, underwent a pharmacokinetic-dynamic assessment.ResultsWe included 53 PD patients. After a mean of 51.7 ± 34.1 months of LCIG treatment, "off-time" was significantly reduced, whereas, dyskinesia duration/disability did not change. The multivariate regression model, adjusted for LCIG treatment duration, showed that being female increases the risk of presenting troublesome dyskinesia at T1 (odds ratio [OR] = 9.2; 95% confidence interval [CI] = 2.4-37.4) that was also significantly associated to longer off periods at T1 (OR= 4.4; 95% CI = 1.1-14.3). Female patients showed a higher risk for a higher dyskinesia score at T1 (sum of the items 32 and 33: P = 0.001). Patients with troublesome dyskinesia showed a tendency for a lower motor benefit and the appearance of more severe dyskinesia despite similar levodopa plasma concentration.ConclusionDyskinesia should be carefully monitored in patients undergoing LCIG, with particular caution for female patients. Whether combined clinical and pharmacodynamic assessments could be helpful to manage patients with troublesome dyskinesia under LCIG treatment needs further evaluation in a larger group of patients.
| S-EPMC7604637 | biostudies-literature
Project description:Levodopa-carbidopa intestinal gel (LCIG) has shown to be efficacious in motor and non-motor symptoms (NMS). Nevertheless, studies with patient Quality of Life (QoL) as a primary endpoint are scarce. To assess the effect of LCIG on Advanced Parkinson's Disease (APD) patients QoL. Secondarily, the impact on motor symptoms and NMS, emotional well-being, treatment satisfaction, and caregiver QoL, stress, disease burden, anxiety, depression, and work impairment were also investigated. In this prospective, 6-month multicenter postmarketing observational study, LCIG was administered to 59 patients with APD. Endpoints were assessed using validated scales and questionnaires. LCIG significantly improved patient QoL (PDQ-39 mean change ± standard deviation from baseline, -12.8 ± 14.6; P < 0.0001), motor symptoms (UPDRS-III in "On," -6.5 ± 11.8; P = 0.0002), NMS (NMSS, -35.7 ± 31.1; P < 0.0001), mood (Norris/Bond-Lader VAS, -6.6 ± 21.1; P = 0.0297), fatigue (PFS-16, -0.6 ± 1.0; P = 0.0003), depression (BDI-II, -5.1 ± 9.4; P = 0.0002), anxiety (BAI, -6.2 ± 9.6; P < 0.0001), and patient treatment satisfaction (SATMED-Q, 16.1 ± 16.8; P < 0.0001). There were significant correlations between the change from baseline to 6 months between PDQ-39 and UPDRS-IV, NMSS, BAI, BDI-II, AS, and PFS-16 scores, and Norris/Bond-Lader alertness/sedation factor. Caregiver anxiety also improved (Goldberg anxiety scale, -1.1 ± 1.0; P = 0.0234), but the clinical relevance of this finding is questionable. The serious adverse events reported were similar to those previously described for LCIG. In patients with APD, LCIG improves QoL, motor symptoms and NMS, emotional well-being, and satisfaction with the treatment. Improvement in patient QoL is associated with improvements in motor complications, NMS, anxiety, depression, apathy and fatigue. Improvements in patients' QoL does not correspond with improvements in caregivers' QoL or burden.
| S-EPMC8633325 | biostudies-literature
Project description:BackgroundThere are limited data regarding the effectiveness of levodopa-carbidopa intestinal gel (LCIG) for dyskinesia.ObjectiveCompare the effectiveness of LCIG versus oral optimized medical treatment (OMT) for dyskinesia in patients with advanced Parkinson's disease (PD) using the Unified Dyskinesia Rating Scale (UDysRS).MethodsThis phase 3b, open-label, multicenter, 12-week, interventional study (NCT02799381) randomized 63 LCIG naïve patients with advanced PD (UDysRS ≥30) to LCIG (N = 30) or OMT (N = 33) treatment. Dyskinesia impact was assessed at baseline through week 12 using the UDysRS. PD-related motor and non-motor symptoms, and quality of life (QoL) were also assessed.ResultsDyskinesias measured by UDysRS were significantly reduced in the LCIG group (n = 24; -17.37 ± 2.79) compared with the OMT group (n = 26; -2.33 ± 2.56) after 12 weeks (-15.05 ± 3.20; 95% CI, -21.47 to -8.63; P < 0.0001). At week 12, LCIG versus OMT also demonstrated significant improvements in "On" time without troublesome dyskinesia (P = 0.0001), QoL (P < 0.0001), global impression of change (P < 0.0001), activities of daily living (P = 0.0006), and Unified Parkinson's Disease Rating Scale (UPDRS) Part III (P = 0.0762). Treatment-emergent adverse events were reported in 27 (44.3%) patients (LCIG, 18 [64.3%]; OMT, 9 [27.3%]). Serious adverse events occurred in 2 (7.1%) LCIG-treated patients.ConclusionsLCIG significantly reduced dyskinesia compared with OMT. LCIG showed efficacy for treatment of troublesome dyskinesia in patients with advanced PD while demonstrating benefits in both motor and non-motor symptoms and QoL. © 2021 AbbVie Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
| S-EPMC9292774 | biostudies-literature
Project description:Motor complications in Parkinson's disease (PD) are associated with long-term oral levodopa treatment and linked to pulsatile dopaminergic stimulation. L-dopa-carbidopa intestinal gel (LCIG) is delivered continuously by percutaneous endoscopic gastrojejunostomy tube (PEG-J), which reduces L-dopa-plasma-level fluctuations and can translate to reduced motor complications. We present final results of the largest international, prospective, 54-week, open-label LCIG study. PD patients with severe motor fluctuations (>3 h/day "off" time) despite optimized therapy received LCIG monotherapy. Additional PD medications were allowed >28 days post-LCIG initiation. Safety was the primary endpoint measured through adverse events (AEs), device complications, and number of completers. Secondary endpoints included diary-assessed off time, "on" time with/without troublesome dyskinesia, UPDRS, and health-related quality-of-life (HRQoL) outcomes. Of 354 enrolled patients, 324 (91.5%) received PEG-J and 272 (76.8%) completed the study. Most AEs were mild/moderate and transient; complication of device insertion (34.9%) was the most common. Twenty-seven (7.6%) patients withdrew because of AEs. Serious AEs occurred in 105 (32.4%), most commonly complication of device insertion (6.5%). Mean daily off time decreased by 4.4 h/65.6% (P?<?0.001). On time without troublesome dyskinesia increased by 4.8 h/62.9% (P?<?0.001); on time with troublesome dyskinesia decreased by 0.4 h/22.5% (P?=?0.023). Improvements persisted from week 4 through study completion. UPDRS and HRQoL outcomes were also improved throughout. In the advanced PD population, LCIG's safety profile consisted primarily of AEs associated with the device/procedure, l-dopa/carbidopa, and advanced PD. LCIG was generally well tolerated and demonstrated clinically significant improvements in motor function, daily activities, and HRQoL sustained over 54 weeks.
| S-EPMC4674978 | biostudies-literature