Levodopa-carbidopa Intestinal Gel In Patients Research Articles

Tolcapone improves outcomes in patients with Parkinson disease treated by levodopa/carbidopa intestinal gel: A pilot study.

Background:Patients with Parkinson disease (PD) treated with levodopa/carbidopa intestinal gel (LCIG) have higher prevalence of hyperhomocysteinemia and peripheral nerves damage.Objective:The aim of our study was to test the effect of catechol-O-methyl transferase inhibitor tolcapone—as an add-on therapy to LCIG in patients with PD—on homocysteine (HCY) metabolism and nerve conduction study (NCS) parameters.Methods:We evaluated NCS and serum B12, folic acid, and homocysteine in 16 patients with advanced PD on LCIG. Quality of life (QoL) was also assessed. Six subjects were treated with tolcapone add-on therapy (and LCIG dose reduction), 5 with B vitamin supplementation, and 5 without additional treatment.Results:The level of HCY increased among patients without treatment (4.95 ± 12.54), and decreased in the vitamin (–17.73 ± 11.82) and tolcapone groups (–8.81 ± 8.36). Patients with tolcapone demonstrated improvement in polyneuropathic symptoms and signs compared with patients treated with vitamins or those without additional treatment (–0.83, d = 0.961). Although the most robust improvement in NCS parameters were observed with tolcapone, the findings were inconsistent to prove the effect of any intervention. Only tolcapone treatment was associated with improvement in QoL (d = 1.089).Conclusion:Our study indicates potential of tolcapone add-on therapy in LCIG treated patients in control of homocysteine levels, and improvement of polyneuropathic symptoms, as well as QoL.

Problems related to levodopa-carbidopa intestinal gel treatment in advanced Parkinson's disease.

BackgroundContinuous levodopa‐carbidopa intestinal gel (LCIG) diminishes daily “off” time and dyskinesia in patients with advanced Parkinson′s disease (PD). Complications are common with percutaneous endoscopic gastrostomy with a jejunal extension tube (PEG‐J).Aim of the StudyTo report the clinical outcome of LCIG in patients with advanced PD in the years 2006–2014 at Helsinki University Hospital.Patients and MethodsLevodopa‐carbidopa intestinal gel treatment started following PEG‐J placement in patients with advanced PD after successful in‐hospital LCIG trial with a nasojejunal tube. Demographics, PEG‐J procedures, discontinuation of LCIG, complications and mortality were retrospectively analyzed.Results [mean (SD)]Sixty patients with advanced PD [age 68(7) years; duration of PD: 11(4) years] had LCIG treatment for 26(23) months. The majority of patients with advanced PD were satisfied with the LCIG treatment. For 51 patients (85%), the pump was on for 16 hr a day, and for nine patients (15%) it was on for 24 hr a day. After 6 months, the levodopa‐equivalent daily dose (LEDD) had increased by 30% compared to pre‐LCIG LEDD. Sixty patients underwent a total of 156 PEG‐J procedures, and 48 patients (80%) had a total of 143 complications. Forty‐six patients (77%) had 119 PEG‐J or peristomal complications, and 22 patients (37%) had a total of 25 other complications. The most common complications were accidental removal of the J‐tube in 23 patients (38%) and ≥5% weight loss in 18 patients (30%). Fifteen patients discontinued the LCIG after 21 (21) months. At the end of the follow‐up period of 33(27) months, 38 patients were still on LCIG and nine (15%) had died.ConclusionMost patients were satisfied with LCIG treatment. A few patients lost weight whereas the majority had complications with PEG‐J. When LCIG treatment is carried out, neurological and endoscopic units must be prepared for multiple endoscopic procedures.

Levodopa-carbidopa intestinal gel in the treatment of patients with Parkinson disease: results of a 12-month open study

To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs. A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of "off" periods, "on" periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient's diaries) were assessed throughout the whole study. The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of "off" periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of "on" periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of "on" periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study. LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction.

Authors’ Reply to Lambarth: “Levodopa-Carbidopa Intestinal Gel in Patients with Parkinson’s Disease: A Systematic Review”

Authors' Reply to Lambarth : "Levodopa-Carbidopa Intestinal Gel in Patients with Parkinson's Disease: A Systematic Review"

Long-term effectiveness of levodopa-carbidopa intestinal gel in 177 Spanish patients with advanced Parkinson's disease.

To assess long-term effectiveness and tolerability of levodopa-carbidopa intestinal gel (LCIG) in Spanish patients with advanced Parkinson's disease. This was an observational, multicenter, cross-sectional, retrospective study. Data of 177 patients were analyzed. LCIG treatment led to a reduction in the percentage of daily 'off' time (16.2 vs 47.6% before LCIG), an increase in the percentage of daily 'on' time without disabling dyskinesia (55.6 vs 21.6%). Most patients experienced improvements in freezing of gait, tremor, dizziness, fatigue or flat mood. Adverse events related to levodopa, gastrostomy and technical issues were reported in 36.2, 42.4 and 43.5% of patients, respectively. This study confirms the long-term effectiveness and safety profile of LCIG in patients with advanced Parkinson's disease.

Intraduodenal levodopa-carbidopa intestinal gel infusion improves both motor performance and quality of life in advanced Parkinson’s disease

We report the efficacy and adverse effect profile of intraduodenal levodopa-carbidopa intestinal gel (LCIG) infusion from patients treated in a single Australian movement disorder centre. We conducted an open-label, 12month prospective study of treatment with LCIG in patients with advanced Parkinson’s disease in a single tertiary referral hospital unit specialising in movement disorders. Patients with levodopa-responsive, advanced Parkinson’s disease with motor fluctuations despite optimal pharmacological treatment were enrolled and underwent a 16hour daily infusion of LCIG for 12months. Fifteen participants completed the trial. The mean (±standard deviation) improvement in Unified Parkinson’s Disease Rating Scale part III was 37±11%, mean daily “off” period reduced from 6.3±2 to 1.9±2hours, total daily “on” time increased from 10.2±3 to 13.7±2hours, “on” period without dyskinesia increased from 4.5±3 to 7.5±5hours, and 39-item Parkinson’s Disease Questionnaire Summary Index score improved by 32.5±35%. The most common adverse event was reversible peripheral neuropathy secondary to vitamin B12±B6 deficiency (40%), local tube problems (40%), and impulse control disorder (ICD) (27%). No patient had stoma bleeding or peritonitis. All patients with ICD had a past psychiatric diagnosis of depression with or without anxiety and a higher daily levodopa intake at 6 and 12months of LCIG infusion. Intraduodenal LCIG improves motor performance, quality of life and daily “on” period. Prior to and during duodenal LCIG infusion, clinicians should monitor for peripheral neuropathy and vitamin B12 and B6 deficiency, as supplementation can reverse peripheral neuropathy. This trial is registered at Clinicaltrials.gov as CT00335153.

Updated long-term safety from ongoing phase 3 trials of levodopa-carbidopa intestinal gel in patients with advanced Parkinson's disease

Updated long-term safety from ongoing phase 3 trials of levodopa-carbidopa intestinal gel in patients with advanced Parkinson's disease

Updated long-term safety from ongoing phase 3 trials of levodopa-carbidopa intestinal gel in patients with advanced Parkinson's disease

Objectives: To summarize the integrated long-term safety data of levodopa-carbidopa intestinal gel (LCIG/carbidopa-levodopa enteral suspension [CLES]) from four ongoing phase 3 studies through 31 March 2014.

Global Long-Term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results on Non-Motor Symptoms (I3-3B)

Global Long-Term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results on Non-Motor Symptoms (I3-3B)

Global Long-Term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results on Non-Motor Symptoms (P3.004)

Global Long-Term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results on Non-Motor Symptoms (P3.004)

Global Long-term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results in a Subgroup of Patients with Dyskinesia at Baseline (P1.192)

Global Long-term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results in a Subgroup of Patients with Dyskinesia at Baseline (P1.192)

1.: Levodopa-carbidopa intestinal gel infusion improves motor performance and quality of life in patients with advanced Parkinson’s disease

We report the efficacy and adverse effect profile of intraduodenal levodopa-carbidopa intestinal gel (LCIG) infusion from the largest case series in an Australian movement disorder center at Westmead Hospital. An open-label, 12 months prospective study (Clinicaltrials.gov identifier: NCT00335153) of treatment with LCIG in patients with advanced Parkinson's disease was conducted. Patients with motor fluctuations despite optimal pharmacological treatment were included. Patients were given a16 hour daily infusion of LCIG for mean of 22±10 months. Minnesota Impulse Disorders Interview (MIDI), complications, the total levodopa daily equivalent dose, Unified Parkinson's Disease Rating Scale (UPDRS) part III, daily hours "off", daily hours "on" without dyskinesia, daily total hours "on" and pre-existing psychiatric diagnosis or impulse control disorder (ICD) was collected at baseline, 3, 6 and 12 months. The study was approved by the Human Research Ethic Committee at Western Sydney Area Health Service. Fifteen patients participated. Mean improvement in UPDRS part III was 37±11%. Mean daily "off" period reduced from 6.3±2 to 1.9±2 hours; total daily "on" time increased from 10.2±3 to 13.7±2 hours; "on" period without dyskinesia increased from 4.5±3 to 7.5±5 hours; 39-item Parkinson's Disease Questionnaire Summary Index improved by 32.5±35%. The most common adverse event was peripheral neuropathy secondary to vitamin B12±vitamin B6 deficiency (67%), local tube problems (60%), impulse control disorder (47%), and stoma infection (30%). No patient had stoma bleeding or peritonitis. All patients with impulse control disorder had a past psychiatric diagnosis and a higher daily levodopa intake at 6 months of LCIG infusion. Intraduodenal LCIG improves motor performance, quality of life and daily "on" period. Our rate of intestinal tube problem or infection was similar to reported literature. Prior to and during duodenal LCIG infusion, clinicians should monitor for peripheral neuropathy and vitamin B12 and B6 deficiency, as supplementation can reverse peripheral neuropathy. Our study suggests that an increased daily levodopa dose compared to baseline is associated with a later development of impulse control disorders, but larger sample studies are needed to confirm this finding.

Safety Analyses from Open-Label Clinical Trials of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease: Events Not Related to Device or Procedure (P7.083)

Safety Analyses from Open-Label Clinical Trials of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease: Events Not Related to Device or Procedure (P7.083)

Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study

Levodopa is the most effective therapy for Parkinson's disease, but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiological, intermittent administration of the drug, and can be reduced with continuous delivery. We aimed to assess efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube. In our 12-week, randomised, double-blind, double-dummy, double-titration trial, we enrolled adults (aged ≥ 30 years) with advanced Parkinson's disease and motor complications at 26 centres in Germany, New Zealand, and the USA. Eligible participants had jejunal placement of a percutaneous gastrojejunostomy tube, and were then randomly allocated (1:1) to treatment with immediate-release oral levodopa-carbidopa plus placebo intestinal gel infusion or levodopa-carbidopa intestinal gel infusion plus oral placebo. Randomisation was stratified by site, with a mixed block size of 2 or 4. The primary endpoint was change from baseline to final visit in motor off-time. We assessed change in motor on-time without troublesome dyskinesia as a prespecified key secondary outcome. We assessed efficacy in a full-analysis set of participants with data for baseline and at least one post-baseline assessment, and imputed missing data with the last observation carried forward approach. We assessed safety in randomly allocated patients who underwent the percutaneous gastrojejunostomy procedure. This study is registered with ClinicalTrials.gov, numbers NCT00660387 and NCT0357994. From baseline to 12 weeks in the full-analysis set, mean off-time decreased by 4.04 h (SE 0.65) for 35 patients allocated to the levodopa-carbidopa intestinal gel group compared with a decrease of 2.14 h (0.66) for 31 patients allocated to immediate-release oral levodopa-carbidopa (difference -1.91 h [95% CI -3.05 to -0.76]; p=0.0015). Mean on-time without troublesome dyskinesia increased by 4.11 h (SE 0.75) in the intestinal gel group and 2.24 h (0.76) in the immediate-release oral group (difference 1.86 [95% CI 0.56 to 3.17]; p=0.0059). In the safety analyses 35 (95%) of 37 patients allocated to the levodopa-carbidopa intestinal gel group had adverse events (five [14%] serious), as did 34 (100%) of 34 patients allocated to the immediate-release oral levodopa-carbidopa group (seven [21%] serious), mainly associated with the percutaneous gastrojejunostomy tube. Continuous delivery of levodopa-carbidopa with an intestinal gel offers a promising option for control of advanced Parkinson's disease with motor complications. Benefits noted with intestinal gel delivery were of a greater magnitude than were those obtained with medical therapies to date, and our study is, to our knowledge, the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study. AbbVie.

Role of magnetic resonance spectroscopy in differentiating parkinsonian syndromes of various etiologies

Role of magnetic resonance spectroscopy in differentiating parkinsonian syndromes of various etiologies

Randomized, Double-Blind, Double-Dummy Study of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson's Disease: Efficacy Analyses by Subgroups (S23.003)

Randomized, Double-Blind, Double-Dummy Study of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson's Disease: Efficacy Analyses by Subgroups (S23.003)

Interim Results from an International, Open-Label Study of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson's Disease: Efficacy Analyses by Subgroups (P01.060)

Interim Results from an International, Open-Label Study of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson's Disease: Efficacy Analyses by Subgroups (P01.060)