title: Continuous intra jejunal infusion of levodopa-carbidopa intestinal gel by jejunal extension tube placement through percutaneous endoscopic gastrostomy for patients with advanced Parkinson's disease: a preliminary study.
abstract: Levodopa is the gold standard in the pharmacological treatment of Parkinson's disease (PD) and its oral administration is associated with the development of disabling motor and non-motor complications in advanced disease. Levodopa is rapidly metabolized and has a short plasma half-life thus requiring frequent, repeated dosing. Impaired gastric emptying is common in PD, and likely contributes to the unpredictable motor responses observed with orally-dosed levodopa. A new therapeutic protocol for patients with advanced PD include a carbidopa/levodopa combination using continuous, modulated enteral administration achieved inserting a Jejunal Extension Tube Placement through Percutaneous Endoscopic Gastrostomy (PEG-J). The aim of this work is to assess efficacy and safety of levodopa-carbidopa intestinal gel (LCIG) delivered continuously through an intrajejunal percutaneous tube (PEG-J).
  
  
  
  We enrolled 11 adults with advanced PD and preserved sensitivity to L-dopa. For pre-procedural endoscopic evaluation each patient underwent a diagnostic esophagogastroduodenoscopy (EGD) 7 days before PEG-J placement to evaluate the presence of gastric anatomical or wall anomalies and the presence of oesophageal or gastric varices. Treatment with LCIG, consisting of a water-based suspension containing micronized levodopa (20 mg/mL) and carbidopa (5 mg/mL) in methylcellulose (Duodopa®), was administered by continuous jejunal infusion for 12h/day using a portable pump (CADD-Legacy) by PEG-J. Clinical evaluations were performed at baseline (T0) before LCIG initiation, and after 3 (T3) and 6 (T6) months of therapy. The efficacy and safety outcomes were assessed by using the Unified Parkinson's Disease Rating Scale (UPDRS) parts II, III and IV.
  
  
  
  Mean age of patients was 71.18 ± 5.4 SD at LCIG initiation. Out of the 11 patients, 2 (18%) dropped-out LCIG at T3. Patients showed statistically significant (p < 0.05) higher performances in activities of daily living and a statistically significant (p < 0.001) lower incidence and severity of motor fluctuations, as rating by UPDRS part IV, compared to their best oral therapy. During observational period, 5 patients experienced adverse events. Success rate for PEG-J placement was 100%.
  
  
  
  Our work shows that continuous intrajejunal infusion of LCIG ensures a reduction in motor Fluctuations compared to oral administration of levodopa-carbidopa in advanced PD. Based on our results and on the evidence emerging in the literature, this therapeutic approach should be the gold standard for therapy in these patients.
authors.affiliation: Endoscopy Unit, Department of Clinical and Experimental Medicine "Magrassi e Lanzara", Second University of Naples, Naples, Italy. zulli.claudio@gmail.com.
authors.forename: C
authors.initials: C
authors.lastname: Zulli
authors.forename: M
authors.initials: M
authors.lastname: Sica
authors.forename: R
authors.initials: R
authors.lastname: De Micco
authors.forename: A
authors.initials: A
authors.lastname: Del Prete
authors.forename: M R
authors.initials: MR
authors.lastname: Amato
authors.forename: A
authors.initials: A
authors.lastname: Tessitore
authors.forename: F
authors.initials: F
authors.lastname: Ferraro
authors.forename: P
authors.initials: P
authors.lastname: Esposito
mesh_terms: D000203:Activities of Daily Living; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D002230:Carbidopa / Q000008:administration & dosage*; D004338:Drug Combinations; D016099:Endoscopy, Gastrointestinal / Q000379:methods*; D005774:Gastrostomy; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage*; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D002230:Carbidopa