Effect of Probiotic on Constipation in Patients With Parkinson's Disease

The aim of the study is to collect data for the assessment of the Lactobacillus casei DG (Enterolactis® duo) effect on overall abdominal pain, bowel movements and other abdominal symptoms and on neuropsychological performance in patients with Parkinson's Disease. The investigators suppose that, due to the immunomodulatory action of probiotics, overall neuropsychological function will improve as well as due also to prebiotic abdominal symptoms will decrease following consumption of Lactobacillus casei DG (Enterolactis® duo).

• Lactobacillus casei DG (Enterolactis duo®) (Dietary supplement): Lactobacillus casei DG (Enterolactis duo®)

Primary outcomes

• satisfaction with therapy [12 weeks]: A "satisfaction with therapy" score (on a 7-point Likert scale: 1 = extremely dissatisfied, 2 = very dissatisfied, 3 = dissatisfied, 4 = partially satisfied, 5 = satisfied, 6 = very satisfied, 7 = extremely satisfied)
• Improvement after treatment [12 WEEKS]: "Improvement after treatment" was evaluated with a global rating-of-change scale (-7 to +7: -7 = extremely worsened, 0 = unchanged, +7 = extremely improved). "Improvement after treatment" was defined by an increase in the global rating-of-change scale of ≥2 points.
• neuropsychological function [12 weeks]: The Non-Motor Symptoms Scale (NMSS) is a 30-item rater-based scale that assesses a wide range of non-motor symptoms in patients with Parkinson's disease (PD). The NMSS measures the severity and frequency of non-motor symptoms across nine dimensions. The scale can be used for patients at all stages of PD.The total NMSS score ranges from 0 to 360, the worst.

Secondary outcomes

• the Unified Parkinson Disease Rating Scale (UPDRS, italian version) [12 WEEKS]: the Unified Parkinson Disease Rating Scale (UPDRS, italian version). The UPDRS is a rating tool used to gauge the course of Parkinson's disease in patients. A score of 199 on the UPDRS scale represents the worst (total disability) with a score of zero representing (no disability); The Non-motor-symptoms scale (NMSS, italian version)
• M-PAC SYM [12 WEEKS]: M-PAC-SYM)5 The Patient Assessment of Constipation Symptoms (scoring from 0 = absent to 4 = very strong)

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* A positive diagnosis of functional constipation or Irritable Bowel Syndrome -subtype constipation according to Rome IV criteria.
* Negative for colon cancer screening
* Negative relevant additional screening or consultation whenever appropriate.
* Ability of conforming to the study protocol.
* Stable treatment for Parkinson's disease

Exclusion Criteria:

* Presence of any other relevant organic, systemic or metabolic disease (particularly significant history of cardiac, renal, oncology, endocrinology, metabolic or hepatic disease), or abnormal laboratory values that will be deemed clinically significant on the basis of predefined values a part from Parkinson's disease
* Ascertained intestinal organic diseases, including ascertained celiac disease or inflammatory bowel diseases (Crohn's disease, ulcerative colitis, diverticular disease, infectious colitis, ischemic colitis, microscopic colitis).
* Previous major abdominal surgeries.
* Inability to conform with protocol.
* Recent history or suspicion of alcohol abuse or drug addiction.
* Previous participation in this study.

• Results publication: Erro R, Picillo M, Vitale C, Amboni M, Moccia M, Longo K, Cozzolino A, Giordano F, De Rosa A, De Michele G, Pellecchia MT, Barone P. Non-motor symptoms in early Parkinson's disease: a 2-year follow-up study on previously untreated patients. J Neurol Neurosurg Psychiatry. 2013 Jan;84(1):14-7. doi: 10.1136/jnnp-2012-303419. Epub 2012 Sep 19. PMID 22993448
• Results publication: Fasano A, Visanji NP, Liu LW, Lang AE, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol. 2015 Jun;14(6):625-39. doi: 10.1016/S1474-4422(15)00007-1. PMID 25987282
• Results publication: Martinez-Martinez MI, Calabuig-Tolsa R, Cauli O. The effect of probiotics as a treatment for constipation in elderly people: A systematic review. Arch Gerontol Geriatr. 2017 Jul;71:142-149. doi: 10.1016/j.archger.2017.04.004. Epub 2017 Apr 14. PMID 28467916
• Results publication: Bellini M, Usai-Satta P, Bove A, Bocchini R, Galeazzi F, Battaglia E, Alduini P, Buscarini E, Bassotti G; ChroCoDiTE Study Group, AIGO. Chronic constipation diagnosis and treatment evaluation: the "CHRO.CO.DI.T.E." study. BMC Gastroenterol. 2017 Jan 14;17(1):11. doi: 10.1186/s12876-016-0556-7. PMID 28088179
• Results publication: Neri L, Iovino P; Laxative Inadequate Relief Survey (LIRS) Group. Bloating is associated with worse quality of life, treatment satisfaction, and treatment responsiveness among patients with constipation-predominant irritable bowel syndrome and functional constipation. Neurogastroenterol Motil. 2016 Apr;28(4):581-91. doi: 10.1111/nmo.12758. Epub 2016 Feb 12. PMID 26867677
• Results publication: Cappello C, Tremolaterra F, Pascariello A, Ciacci C, Iovino P. A randomised clinical trial (RCT) of a symbiotic mixture in patients with irritable bowel syndrome (IBS): effects on symptoms, colonic transit and quality of life. Int J Colorectal Dis. 2013 Mar;28(3):349-58. doi: 10.1007/s00384-012-1552-1. Epub 2012 Aug 12. PMID 22885882

• PAOLA IOVINO, MD, Principal investigator, University of Salerno