Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson's Disease

NCT04871464 | Unknown Phase 4

• 1 other identifier: 2019-P2-153-02
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 10

Brief Summary

This study is a multicenter randomized double-blind placebo-controlled study. The research content is 1. The improvement effect of Bifidobacterium triple viable capsules（BIFICO） on motor symptoms and constipation and sleep in mild to moderate Parkinson's disease and the safety of the study; 2. the mechanism of the improvement effect of intestinal microecological changes on motor and constipation symptoms in mild to moderate Parkinson's disease.

Conditions

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Movement Disorders; Neurodegenerative Diseases; Central Nervous System Diseases; Nervous System Diseases

Keywords

Parkinson's disease; Probiotics

Outcome Measures

Primary Outcomes (1)

• Movement Disorder Society Unified Parkinson's Disease Rating Scale(MDS-UPDRS)Ⅱ+Ⅲ

  Part Ⅱ：This measures the motor aspects of activity of daily living and consists of 13 items with scores between 0- 52. Part Ⅲ：This measures the severity of motor symptoms using 18 items (score 0-72). Higher score indicates high severity.

  12 weeks

Secondary Outcomes (9)

• Proportion of MDS-UPDRS II+III total score change <3 points

  12 weeks

• Movement Disorder Society Unified Parkinson's Disease Rating Scale(MDS-UPDRS)Ⅱ+Ⅲ

  24 weeks

• Proportion of MDS-UPDRS II+III total score change <3 points

  24 weeks

• Movement Disorder Society Unified Parkinson's Disease Rating Scale(MDS-UPDRS) part Ⅰ

  12 weeks and 24 weeks

• Cleveland Constipation Score（ CCS），Rome Ⅲ Diagnostic Criteria for Constipation

  12 weeks and 24 weeks

Study Arms (3)

Probiotics

EXPERIMENTAL

Bifidobacterium triple viable capsules（BIFICO），containing Bifidobacterium longum, Lactobacillus acidophilus and Enterococcus faecalis(each ≥ 1.0×10\^7 CFU/capsule)，Day 1-14, 2 capsules twice daily; Day 15-24 weeks, 4 capsules twice daily, taken orally half an hour after meals.

Drug: Live Combined Bifidobacterium,Lactobacillus and Enterococcus Capsules

Placebo

PLACEBO COMPARATOR

Placebo，day 1-14, 2 capsules twice daily; Day 15-24 weeks, 4 capsules twice daily, taken orally half an hour after meals.

Other: Placebo

Healthy control

NO INTERVENTION

Healthy subjects without constipation matched for age and sex to PD subjects

Interventions

Live Combined Bifidobacterium,Lactobacillus and Enterococcus Capsules DRUG

Oral

Also known as: BIFICO

Probiotics

Placebo OTHER

Oral

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40-85 years old, both male and female;
• Patients with primary Parkinson's disease who meet the 2015 MDS clinical diagnostic criteria; PD with modified Hoehn-Yahr stage 1-3 and MDS-UPDRS II+III score ≥ 14 and no significant off periods or off periods ≤ 1.5 hours per day (excluding morning motor inability);
• Pre-enrollment therapeutic medications included Levodopa complex preparation, and all Parkinson's disease medications were unadjusted and motor symptoms were stable for 28 days prior to enrollment;
• No probiotic or/and prebiotic (including lactulose) and antibiotic therapy for 60 days prior to enrollment, and if so, a 60-day washout period;
• Understand and agree to follow the study protocol, agree to be enrolled and sign the informed consent form.

You may not qualify if:

• Parkinson's superimposed syndrome and secondary Parkinson's syndrome, such as multiple system atrophy, progressive supranuclear palsy, etc.；
• Taking any probiotic or prebiotic (including lactulose) within 60 days prior to enrollment; having inflammation at any site and using any antibiotic within 60 days prior to enrollment; or having blood leukocytes above the upper limit of normal at screening；
• Combined endocrine disorders, such as history of diabetes or fasting glucose ≥ 7.8 mmol/L;
• Gastrointestinal tumors, history of inflammatory bowel disease, other acute and chronic inflammation of the gastrointestinal tract (including acute attacks of cholecystitis) within 3 months；
• History of gastrointestinal surgery (excluding endoscopic resection of gastrointestinal benign polyps, appendicitis resection) or constipation caused by surgery；
• History of anal fissure, perianal abscess, irreversible anal prolapse, pelvic trauma；
• Severe cardiovascular disease (such as congestive heart failure with a heart function classification of Ⅲ-Ⅳ by the American Heart Association, a history of myocardial infarction within 6 months, etc.);
• Severe liver and kidney dysfunction with glutamate-pyruvate transaminase, aspartate transaminase and total bilirubin 2.0 times higher than the upper limit of normal; serum creatinine 2.0 times higher than the upper limit of normal;
• Pregnant and lactating women or women of childbearing age (40-60 years) who are human chorionic gonadotropin (HCG)-positive;
• Known allergy to test drugs or related products;
• People with a history of drug abuse or alcohol dependence;
• Those who have participated in other clinical trials within 3 months prior to enrollment;
• Refusal to enroll and inability to cooperate with the investigator; patients judged by the investigator to be unsuitable for enrollment.

Sponsors & Collaborators

• Beijing Friendship Hospital: lead

Study Sites (10)

China-Japan Friendship Hospital

Beijing, Beijing Municipality, 100029, China

NOT YET RECRUITING

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

NOT YET RECRUITING

Beijing Friendship Hospital

Beijing, Beijing Municipality, 100050, China

RECRUITING

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

NOT YET RECRUITING

Xuanwu Hospital Capital Medical University

Beijing, Beijing Municipality, 100053, China

NOT YET RECRUITING

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

NOT YET RECRUITING

Beijing Hospital

Beijing, Beijing Municipality, 100730, China

NOT YET RECRUITING

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

NOT YET RECRUITING

Jinan Central Hospital

Jinan, Shandong, 250013, China

NOT YET RECRUITING

Shanghai Changzheng Hospital

Shanghai, Shanghai Municipality, 200003, China

NOT YET RECRUITING

Related Publications (6)

• Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell. 2016 Dec 1;167(6):1469-1480.e12. doi: 10.1016/j.cell.2016.11.018.

  PMID: 27912057 BACKGROUND

• Barichella M, Pacchetti C, Bolliri C, Cassani E, Iorio L, Pusani C, Pinelli G, Privitera G, Cesari I, Faierman SA, Caccialanza R, Pezzoli G, Cereda E. Probiotics and prebiotic fiber for constipation associated with Parkinson disease: An RCT. Neurology. 2016 Sep 20;87(12):1274-80. doi: 10.1212/WNL.0000000000003127. Epub 2016 Aug 19.

  PMID: 27543643 BACKGROUND

• Tamtaji OR, Taghizadeh M, Daneshvar Kakhaki R, Kouchaki E, Bahmani F, Borzabadi S, Oryan S, Mafi A, Asemi Z. Clinical and metabolic response to probiotic administration in people with Parkinson's disease: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2019 Jun;38(3):1031-1035. doi: 10.1016/j.clnu.2018.05.018. Epub 2018 Jun 1.

  PMID: 29891223 BACKGROUND

• Kim S, Kwon SH, Kam TI, Panicker N, Karuppagounder SS, Lee S, Lee JH, Kim WR, Kook M, Foss CA, Shen C, Lee H, Kulkarni S, Pasricha PJ, Lee G, Pomper MG, Dawson VL, Dawson TM, Ko HS. Transneuronal Propagation of Pathologic alpha-Synuclein from the Gut to the Brain Models Parkinson's Disease. Neuron. 2019 Aug 21;103(4):627-641.e7. doi: 10.1016/j.neuron.2019.05.035. Epub 2019 Jun 26.

  PMID: 31255487 BACKGROUND

• Qian Y, Yang X, Xu S, Wu C, Song Y, Qin N, Chen SD, Xiao Q. Alteration of the fecal microbiota in Chinese patients with Parkinson's disease. Brain Behav Immun. 2018 May;70:194-202. doi: 10.1016/j.bbi.2018.02.016. Epub 2018 Mar 2.

  PMID: 29501802 BACKGROUND

• Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, Kinnunen E, Murros K, Auvinen P. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord. 2015 Mar;30(3):350-8. doi: 10.1002/mds.26069. Epub 2014 Dec 5.

  PMID: 25476529 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Movement Disorders; Neurodegenerative Diseases; Central Nervous System Diseases; Nervous System Diseases

Interventions

Lacteol

Condition Hierarchy (Ancestors)

Synucleinopathies

Study Officials

• Houzhen Tuo, PhD

  Beijing Friendship Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Houzhen Tuo, PhD

CONTACT

+8613683628005; tuohouzhen@ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Study is double blind design
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-Director of Neurology

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 4, 2021
• Study Start: November 11, 2021
• Primary Completion: October 1, 2023
• Study Completion: December 1, 2023
• Last Updated: February 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)