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Title: Gastroparesis symptoms in Parkinson's disease : correlation with motor and non-motor symptoms and exploration of a novel drug to improve gastric emptying
Author: Marrinan, Sarah Louise
ISNI:       0000 0004 5370 0529
Awarding Body: University of Newcastle upon Tyne
Current Institution: University of Newcastle upon Tyne
Date of Award: 2015
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Background: Parkinson’s disease (PD) can result in impaired motility throughout the gastrointestinal tract. Delayed gastric emptying or gastroparesis is estimated to affect over 70% of all people with PD. However, the prevalence of gastroparesis symptoms in people with PD is unknown. This study sought to define the prevalence and associated features of gastroparesis symptoms in people with PD. Methods: More than 1,000 people with PD completed the Gastroparesis Cardinal Symptom Index (GCSI), a validated structured questionnaire to assess the presence and severity of gastroparesis symptoms. Two groups of patients were recruited to this UK wide study: those with recently diagnosed PD (within the last three years) and those with young onset disease (diagnosed before the age of 50). Results: More than half of the 1,003 participants reported at least one gastroparesis symptom in the two weeks prior to completing the GCSI questionnaire. In those with recently diagnosed PD (n = 691) only 4.1% had a GCSI total score consistent with significant gastroparesis. In the young onset group 12.5% of participants had symptoms in keeping with gastroparesis. Features associated with a greater gastroparesis symptom burden across both groups included more advanced PD features, more non-motor symptoms, autonomic symptoms, anxiety and depression. Conclusions: Although delayed gastric emptying is estimated to affect over 70% of all people with PD, in this large study we found that significant gastroparesis symptoms were only reported by 4-12% of patients. This suggests that although gastroparesis is a common abnormality in PD it may be largely asymptomatic. ii Abstract 2 Exploration of a novel treatment for delayed gastric emptying in Parkinson’s disease Background: Delayed gastric emptying can impair Levodopa absorption and contribute to motor fluctuations in people with PD. Prokinetic medications may improve gastric emptying and consequently Levodopa absorption and motor function. However, there are few licenced prokinetics suitable for use in PD. This is an interim report of an on-going Phase II, double blind, placebo controlled study to assess the effect of a novel motilin agonist (Camicinal) on Levodopa absorption in people with PD, delayed gastric emptying and motor fluctuations. Methods: 15 patients with PD were enrolled in this study. All had bilateral disease (Hoehn & Yahr stage II-IV) and troublesome motor fluctuations. There were 9 men and 6 women with a mean age of 64.40 (± 10.32) years. Participants were randomised to Camicinal 50mg (n=10) or placebo (n=5) once daily for 7-9 days. The treatment and placebo group were matched for clinical and demographic features. Clinical and pharmacokinetic parameters were measured serially at baseline, on the first day of treatment and the final dosing day. Statistical analyses were performed using non-parametric tests. Results: Camicinal was as well tolerated as placebo. By the end of the dosing period there was a non-significant trend towards increased Levodopa absorption (Cmax) in the Camicinal treated group but not the placebo group. Gastric emptying rates and gastroparesis symptoms did not change significantly in either group. There was a significant improvement in motor function (reduced MDS UPDRS Part III score) in the treatment group by the end of the dosing period compared with baseline (P < 0.05). The percentage of the waking day spent in the ‘off’ state fell in the Camicinal group and rose in the placebo group. Conclusions: These interim results suggest that Camicinal has potential as a novel therapy to enhance Levodopa absorption and motor function in people with PD. Therefore on-going study and evaluation of this agent is justified.
Supervisor: Not available Sponsor: Parkinson's UK ; GSK ; Michael J Fox Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available