Levodopa-carbidopa Intestinal Gel Therapy Research Articles

Age/disease duration influence on activities of daily living and quality of life after levodopa-carbidopa intestinal gel in Parkinson's disease.

To determine if age and Parkinson's disease duration at therapy initiation influence the efficacy of levodopa-carbidopa intestinal gel (LCIG) on quality of life and activities of daily living. This post hoc analysis assessed subgroups of patients stratified by baseline age, disease duration, hours/day of 'off' time and levodopa equivalent dose. Patients' data were collected from the GLORIA study, a 24-month observational registry evaluating long-term effectiveness of LCIG. LCIG therapy led to sustained improvements in quality of life irrespective of patient age and disease duration at baseline. Improvements in activities of daily living were observed across all subgroups, particularly in younger patients, patients with shorter disease duration and in patients with the highest baseline levodopa equivalent dose.

Levodopa-carbidopa intestinal gel treatment introduced by surgical gastrostomy in a patient of Parkinson's disease after Billroth II gastrojejunostomy

A 68-year-old man, who had received Billroth II gastrojejunostomy because of duodenal ulcer at the age of 20, was diagnosed to have Parkinson's disease at age 57 years. The drug therapy has been effective in the first 10 years, however, recently he was suffering from troublesome dyskinesia and wearing-off in spite of diligent drug adjustments. Although the indication of levodopa-carbidopa intestinal gel (LCIG) treatment was good, percutaneous endoscopic gastrostomy was difficult because of abdominal adhesion. Therefore, we introduced LCIG by surgical gastrostomy. After LCIG therapy, wearing-off and dyskinesia disappeared. This is the first case of Parkinson's disease patient with LCIG therapy by surgical gastrostomy in Japan.

Peripheral neuropathy in 30 duodopa patients with vitamins B supplementation.

Peripheral neuropathy (PN) is a significant concern and potential cause of withdrawal in patients with Parkinson's disease (PD) treated with Levodopa/Carbidopa Intestinal Gel (LCIG) infusion. Vitamin B deficiency and/or hyperhomocysteinemia levodopa-related are considered possible causative factors. In this study, we evaluated PN incidence in LCIG-PD patients treated since the beginning of infusion with vitamins B supplementation. In this prospective open-label pilot study, 30 consecutive patients with PD on LCIG infusion were evaluated with clinical, neurophysiological, and biochemical assessments for a mean follow-up of 42.4months (range 24-72). All evaluations were repeated every 6months. At baseline, 21 of 30 presented no signs or symptoms of PN, and 9 of 30 had pre-existing chronic PN. In whole population, a progressive worsening in nerve conduction studies of sural sensory and peroneal motor nerves was observed during the long-term follow-up. 4 of 21 patients, with normal clinical, electrophysiological assessment at baseline, developed distal symmetrical axonal polyneuropathy that remained asymptomatic during the long-term follow-up. Patients with pre-existing PN (9 of 30) showed a mild worsening of electrophysiological features during the period of observation. In none PN was cause of discontinuation of LCIG therapy. No incident cases of acute-subacute PN were documented. No correlation was found with age, sex, Levodopa dosage, duration of levodopa exposure, and homocysteine plasma levels. In this consecutive series of 30 patients with PD on LCIG infusion, with early and continuous vitamins B integration, we observed a low rate (19%) of new onset peripheral polyneuropathy that remained stable after long-term follow-up. Larger studies, controlled, with blinded evaluation, are needed to confirm these findings.

Levodopa/carbidopa intestinal gel (LCIG) infusion as mono- or combination therapy.

Levodopa/carbidopa intestinal gel (LCIG) infusion is an effective escalating therapy in patients with Parkinson disease (PD) suffering from motor fluctuations and dyskinesia. Levodopa/carbidopa given continuously as infusion provides an optimized application of the most effective and best tolerable antiparkinsonian drug. It has been proven to have a superior motor effect compared with oral levodopa and to improve also non-motor symptoms. However, invasiveness, discomfort resulting from carrying an external device, and side effects associated with the way of administration limit its application in PD patients. At present, there are no guidelines that delineate to which patients LCIG should be offered as monotherapy, in combination with oral and/or transdermal medication, or as additional therapy to deep brain stimulation (DBS). Based on clinical studies, we propose an expert consensus for neurologists addressing the question when LCIG therapy should be recommended and in which cases LCIG infusion is suggested in combination with other antiparkinsonian drugs and/or DBS. We describe how LCIG should be initiated and what we consider necessary for clinical follow-up. We suggest an algorithm facilitating decision-making with respect to the currently available invasive PD therapies, namely infusion with subcutaneous apomorphine, LCIG, and DBS.

Which patients discontinue? Issues on Levodopa/carbidopa intestinal gel treatment: Italian multicentre survey of 905 patients with long-term follow-up

ObjectivesTo report the results of a national survey aimed at quantifying the current level of diffusion of Levodopa/carbidopa intestinal gel (LCIG) in Italy. MethodsSixty Parkinson's Disease (PD) specialists in Italy were invited to complete a survey covering issues on clinical and practical aspects of LCIG therapy. ResultsClinical features of 905 patients were collected retrospectively. The majority of centres reported the use of a multidisciplinary team, biochemistry testing, neurophysiological and neuropsychological tests before and after treatment, in addition to caregivers' training and patient's follow as outpatients. Most centres (60%) used internal guidelines for patient selection. The overall rate of adverse events was 55.1%. Weight loss, chronic polyneuropathy and stoma infection were the most frequently reported. 40% of centres used replacement therapy with Vitamin B12 and Folic acid from the start of LCIG and continued this for the duration of treatment. The rate of discontinuation was of 25.7% overall, with 9.5% of cases occurring in the first year. The main causes of withdrawal were device-related complications, disease progression (comorbidity, severe dementia) and caregiver and/or patient dissatisfaction. ConclusionsIn Italy LCIG infusion is managed in a uniform manner at a clinical, practical and organizational level even though the selection criteria are not standardized through the country. The high percentage of patients remaining on treatment in the short- and long-term follow-up confirms effectiveness of treatment, careful follow-up, and appropriate patient and caregivers training.

Infusional Therapies, Continuous Dopaminergic Stimulation, and Nonmotor Symptoms.

Pump-based Parkinson (PD) therapies, including subcutaneous apomorphine infusion (CSA) and levodopa-carbidopa intestinal gel (LCIG), presently constitute the most effective pharmacological treatments available for advanced PD. These therapies are based on a more constant delivery of the dopaminergic drug resulting in a more continuous dopaminergic stimulation and a more stable treatment effect. This can be detected as reduction of time in off, reduction of dyskinesia frequency and severity, as well as increase of time in on without troublesome dyskinesias. A number of open-label studies now suggest that also the nonmotor PD symptomatology can improve under CSA and LCIG therapy. The most consistent improvements are seen concerning sleep, mood, and apathy, gastrointestinal symptoms, and urological symptoms. But also cardiovascular symptoms, perception, attention, and sexual function might show beneficial effects when moving from conventional therapies to pump treatment. Further there might be negative influences on some parts of the nonmotor symptomatology through side effects of CSA and LCIG therapy. In this chapter, we review the present knowledge about these aspects of the pump-based therapies. This information might be valuable when deciding on advanced therapy for individual patients.

Diphasic dyskinesias during levodopa-carbidopa intestinal gel (LCIG) infusion in Parkinson's disease

ObjectivesLevodopa-carbidopa intestinal gel infusion (LCIG) is indicated in patients with advanced levodopa-responsive Parkinson's disease (PD) for the treatment of motor fluctuations and dyskinesias. Here we describe 4 PD patients who developed disabling diphasic dyskinesias after LCIG initiation. MethodsThe clinical data of 33 PD patients consecutively treated with LCIG therapy were obtained through direct clinical observation and detailed review of medical records. ResultsWithin 10 days, after LCIG introduction, we identified 4 subjects (12.1%) with persistent and disabling diphasic dyskinesia (DD). We tried to manage these symptoms by increasing morning LCIG flow and adding “extended-release” formulations of dopamine-agonists and levodopa/carbidopa during bedtime. Within 1 month, all patients presented a gradual reduction in the duration and severity of DD. ConclusionsTo our knowledge, this is the first report describing the occurrence of DD in a small cohort of advanced PD patients after LCIG initiation. We wish to draw the attention of clinicians to the risk of developing disabling DD in PD patients switched to the LCIG monotherapy.

Levodopa-Carbidopa Intestinal Gel in Patients with Parkinson's Disease: A Systematic Review.

Levodopa-carbidopa intestinal gel (LCIG) is available in several countries for the treatment of advanced levodopa-responsive Parkinson's disease (PD) with severe motor fluctuations and dyskinesia when other treatments have not given satisfactory results. Our objective was to summarize the present evidence base for LCIG therapy through a systematic review of the literature. Studies were identified from the PubMed and EMBASE databases up to 12 March 2016 using the following search terms: Parkinson disease, duodopa, levodopa/carbidopa intestinal gel, levodopa-carbidopa intestinal gel, LCIG, l-dopa infusion, levodopa infusion, duodenal l-dopa infusion, and duodenal levodopa infusion. Data extraction focused on whether LCIG therapy improves motor and non-motor outcomes as well as quality of life in PD patients compared with conventional therapy, apomorphine infusion, or deep brain stimulation. Randomized controlled trials (RCTs) and observational studies, with or without a control group, that included more than ten patients were included. The search was limited to peer-reviewed articles published in full in the English language and involving humans. Infusion of LCIG reduced "off" time, increased "on" time without increasing troublesome dyskinesias, and improved quality of life in three RCTs (one double-blind). Open-label follow-ups confirm these findings. The data evaluating long-term efficacy and safety are still limited. The quality of evidence that LCIG is effective in reducing fluctuating motor symptoms and improving quality of life is moderate. Quality of evidence for reduction of non-motor symptoms is very low. Safety issues mainly relate to the intestinal infusion system. LCIG might be a useful treatment option in PD patients with severe motor fluctuations.

Clinical management of patients with advanced Parkinson's disease treated with continuous intestinal infusion of levodopa/carbidopa.

Patients with Parkinson's disease often have a good initial response to dopaminergic therapy but later usually develop motor fluctuations and dyskinesia. In these patients, continuous infusion of levodopa-carbidopa intestinal gel (LCIG) allows for maintaining adequate dopamine levels and for improving motor and nonmotor symptoms, as well as quality of life and autonomy. Adequate candidate selection and follow-up are crucial for treatment success. Management should be multidisciplinary, and patient and caregiver education is a priority. This expert consensus document has been developed by a team of neurologists, gastroenterologists and nurses who have a vast experience in LCIG therapy, with an intention to provide knowledge and tools to facilitate patient management throughout all phases of LCIG treatment process.

Levodopa-Carbidopa Intestinal Gel Infusion Therapy in Advanced Parkinson's Disease: Single Middle Eastern Center Experience

Background: Levodopa therapy in Parkinson's disease (PD) is often associated with disabling motor and non-motor complications in patients with advanced disease due to the variable absorption of levodopa because of an irregular or erratic emptying of the gastric content. Methods: Prospective single movement disorder center study using pre-set selection criteria, unified PD scale (UPDRS III), non-motor symptoms scale (NMSS), and PD questionnaire-8 (PDQ-8) to evaluate the efficacy, safety, and long-term treatment outcomes using levodopa-carbidopa intestinal gel (LCIG) infusion in patients with advanced PD, who were followed up every 6 months. Results: Twenty patients were recruited over a period of 6 years. Disease duration prior to LCIG infusion ranged from 5 to 18 years (mean 11.4 ± 4.2). The mean follow-up time on LCIG therapy was 48.5 ± 23.2 months (range 11-83 months). Mean ‘off' time, UPDRS III, NMSS, and PDQ-8 improvement were statistically significant. Two patients dropped out and 66.7% of patients required tube replacement. Conclusion: LCIG infusion monotherapy demonstrated significant improvement in reducing the ‘off' time, reducing levodopa-induced dyskinesia, and improving non-motor symptoms and quality of life. This therapy is recommended for patients in whom motor fluctuations are inadequately treated with traditional oral PD therapy.

Improvement of dyskinesias with L-dopa infusion in advanced Parkinson's disease.

We wanted to investigate whether continuous intrajejunal levodopa-carbidopa intestinal gel (LCIG) therapy has an antidyskinetic effect in patients with Parkinson's disease (PD) and troublesome dyskinesias. We also sought to examine the effect of LCIG therapy on motor function and health-related quality of life (HRQoL). This open-label pilot study used a single group pre-post design with follow-up at 6 months. Nine patients with PD who reported to spend at least 3 h per day in on with troublesome dyskinesia were included. The patients were examined at baseline using clinical and self-assessment measures and then switched from peroral/transdermal pharmacotherapy to LCIG therapy. Data collection was repeated 6 months after the pharmaceutical intervention. Nonparametric statistical methods were used for data analyses. The mean time spent in on with troublesome dyskinesia per day after 6 months of LCIG therapy decreased by 47% (P < 0.05). This observation was paralleled by a 112% increase in mean time spent in on without troublesome dyskinesia (P < 0.01). Patient self-assessment of dyskinesia intensity on the visual analog scale displayed a 90% reduction of mean dyskinesia intensity (P < 0.01) and patients also exhibited less dyskinesia during standardized levodopa tests. Furthermore, we noted improvements in motor function and HRQoL. In this pilot study, we found indications that LCIG therapy has a substantial antidyskinetic effect and could be an alternative also for PD patients with dyskinesias as a major symptom. However, further studies with blinded evaluation and larger numbers of patients are warranted to confirm the findings.

24h Levodopa-carbidopa intestinal gel may reduce falls and "unresponsive" freezing of gait in Parkinson's disease.

We report a prospective, open label study of 24 h levodopa-carbidopa intestinal gel (LCIG) as treatment for levodopa "unresponsive" freezing of gait (FOG) associated with Parkinson's disease. 5 patients with disabling FOG, documented as being levodopa "unresponsive", were commenced on continuous 24 h infusion LCIG therapy with the night-time rate at 50-80% of the daytime infusion rate. Patients underwent baseline, 3 and 6 month gait assessments, documentation of their falls frequency and completed FOG questionnaires. Median 360° turn time improved by 54%, fall frequency score reduced from 3 to 0 at 6 months, FOG questionnaire score improved by 14% and Timed Up- and -Go 8 m walk was unchanged. 24 h LCIG therapy may reduce levodopa "unresponsive" FOG and associated falls. A larger prospective study is needed for confirmation.

Levodopa/carbidopa intestinal gel infusion in advanced Parkinson's disease: a 7‐year experience

Levodopa/carbidopa intestinal gel (LCIG) infusion is nowadays becoming an established therapeutic option for advanced Parkinson's disease (PD) patients with fluctuating symptoms unresponsive to conventional oral treatment. As the implementation of LCIG therapy is increasing, there is a need for safety and efficacy data from current clinical practice. All PD patients treated with LCIG at our centre over a 7-year period were analysed to determine the duration of treatment, retention rate, reasons for discontinuation, LCIG efficacy in motor complications, modifications of concomitant therapy and adverse events. Of the 59 patients, seven subjects (12%) died of causes unrelated to LCIG infusion and 11 patients (19%) discontinued therapy prior to the cut-off date. Duodopa improved motor complications and over 90% of patients reported an improvement in their quality of life, autonomy and clinical global status. The most common adverse events were dislocation and kinking of the intestinal tube. LCIG infusion is effective for the long-term treatment of advanced PD patients and exerts a positive and clinically significant effect on motor complications with a relatively low dropout rate.

Pharmacokinetics of Levodopa, Carbidopa, and 3-O-Methyldopa Following 16-hour Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson’s Disease Patients

Motor complications of Parkinson's disease (PD) are a consequence of pulsatile dopaminergic stimulation from standard oral levodopa therapy. Levodopa-carbidopa intestinal gel (LCIG) is infused continuously via an intrajejunal percutaneous gastrostomy tube. This was the first study designed to characterize the full pharmacokinetic profiles of levodopa, carbidopa, and levodopa metabolite, 3-O-methyldopa (3-OMD) with 16-h LCIG infusion. Nineteen advanced PD patients (mean age, 65 years) who were on LCIG therapy for ≥30 days were enrolled. Patients received their individualized LCIG infusion doses, and serial pharmacokinetic samples were collected. Eighteen patients completed the study; 19 were assessed for safety. Mean (SD) total levodopa and carbidopa doses were 1,580 (403) and 395 (101) mg, respectively. Mean (SD) C(avg) (μg/mL) were 2.9 (0.84) for levodopa, 17.1 (4.99) for 3-OMD, and 0.22 (0.08) for carbidopa. The degree of fluctuation [defined as (C(max)-C(min))/C(avg)] in levodopa, 3-OMD, and carbidopa plasma concentrations was very low (0.52, 0.21, and 0.96, respectively) during hours 2-16 of infusion. Accordingly, the within-subject coefficients of variation in levodopa, 3-OMD, and carbidopa concentrations were low (13%, 6%, and 19%, respectively). Three patients (16%) reported ≥1 treatment-emergent adverse event; none were considered severe. Continuous intrajejunal LCIG infusion maintained stable plasma levodopa levels over 16 h. Consistent exposure has been shown to reduce motor and nonmotor complications associated with oral medications. LCIG was well tolerated, consistent with previous reports.

Refractory epileptic seizures due to vitamin B6 deficiency in a patient with Parkinson’s disease under duodopa® therapy

Levodopa/carbidopa intestinal gel (LCIG) infusion for the treatment of advanced Parkinson's disease (PD) has been suspected to provoke polyneuropathy in conjunction with vitamin B6, B12 and folate deficiency and elevated homocysteine levels. We describe a PD patient under LCIG therapy developing refractory epileptic seizures obviously promoted by vitamin B6 deficiency.