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

February 17, 2023 updated by: Houzhen Tuo, Beijing Friendship Hospital

Role and Mechanism of Bifidobacterium Triple Viable Capsules in Improving Motor Symptoms in Patients With Mild to Moderate Parkinson's Disease: a Multicenter Randomized Clinical Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This was a multicenter randomized double-blind placebo-controlled study that included 240 patients with primary PD with modified H-Y stage 1-3, randomly divided into treatment and placebo control groups; On the basis of the original PD medication, the treatment group was given bifidobacterium triple viable capsules (BIFICO) and the control group was given placebo; Patients who met the diagnosis of constipation were given Macrogol 4000 powder and /or Enema glycerine as a rescue medicine, and the observation period was 12+12 weeks.

All subjects underwent the World Movement Disorders Society Parkinson's Disease Comprehensive Rating Scale (MDS-UPDRS), Rome IV Constipation Diagnostic Scale, Cleveland Rating Scale, Parkinson's Disease Sleep Scale-2 (PDSS-2), and General Clinical Outcome Inventory (CGI) scores before and after treatment, and also recorded the patients' single bowel movement time and the use of Macrogol 4000 powder and Enema glycerine , to investigate the improvement effect of Bifido on motor symptoms and non-motor symptoms in PD patients. For the above patients, stool and blood samples were collected at the time of enrollment and at 12 weeks of observation.

At the same time,120 age-and gender-matched healthy adults without constipation were recruited, and their stool and blood samples were collected; the stool samples of PD patients before and after treatment and healthy controls were subjected to the determination of fecal flora 16S DNA abundance. Stool samples of 10 PD patients and 10 healthy controls were taken from each group for metagenomic sequencing. Detection of small molecule metabolites, PD-related genes in blood. To investigate the effect of BIFICO on levodopa pharmacokinetics, levodopa pharmacokinetic measurements will be performed at Friendship Hospital. For patients who agree to participate and sign the informed consent form, blood specimens will be collected consecutively at Visit 2 and Visit 11 after taking Levodopa and Benserazide Hydrochloride Tablets for levodopa blood concentration measurement.

Study Type

Interventional

Enrollment (Anticipated)

240

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100050
        • Recruiting
        • Beijing Friendship Hospital
        • Contact:
      • Beijing, Beijing, China, 100034
        • Not yet recruiting
        • Peking University First Hospital
        • Contact:
      • Beijing, Beijing, China, 100730
        • Not yet recruiting
        • Beijing hospital
        • Contact:
      • Beijing, Beijing, China, 100029
        • Not yet recruiting
        • China-Japan Friendship Hospital
        • Contact:
          • Miao Jin, PhD
      • Beijing, Beijing, China, 100191
        • Not yet recruiting
        • Peking University Third Hospital
        • Contact:
      • Beijing, Beijing, China, 100730
        • Not yet recruiting
        • Peking Union Medical College Hospital
        • Contact:
      • Beijing, Beijing, China, 100053
        • Not yet recruiting
        • Xuanwu Hospital Capital Medical University
        • Contact:
      • Beijing, Beijing, China, 100050
        • Not yet recruiting
        • Beijing Tiantan Hospital, Capital Medical University
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250013
        • Not yet recruiting
        • Jinan Central Hospital
        • Contact:
          • Shuang Liu, PhD
    • Shanghai
      • Shanghai, Shanghai, China, 200003
        • Not yet recruiting
        • Shanghai Changzheng Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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;
  • Comorbid other neurological disorders, such as cognitive impairment, Mini-Mental State Examination （MMSE） scale score <24; severe anxiety states and/or severe depressive states (Hamilton Depression Inventory-17 item score >17, Hamilton Anxiety Scale score ≥14, or being treated with antidepressant anxiety medication); Note: Those who were taking antidepressant and anxiety drugs and had no adjustment in the last 28 days, and whose score of Hamilton Depression Scale -17 was less than 17, and Hamilton Anxiety Scale score was less than 14 were not included in the exclusion criteria; Severe autonomic nervous disease occurs within 5 years of onset, malignancy, spinal cord lesions, epilepsy, autonomic disorders (urinary retention, urinary incontinence, or upright hypotension , blood pressure drop ≥30/15 mmHg at any time point within 5 minutes of uprightness), etc.; new cerebrovascular disease or sequelae of severe cerebrovascular disease within 6 months, which affects the assessment；
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Probiotics
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
Oral
Other Names:
  • BIFICO
Placebo Comparator: Placebo
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
Oral
No Intervention: Healthy control
Healthy subjects without constipation matched for age and sex to PD subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Movement Disorder Society Unified Parkinson's Disease Rating Scale(MDS-UPDRS)Ⅱ+Ⅲ
Time Frame: 12 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of MDS-UPDRS II+III total score change <3 points
Time Frame: 12 weeks
Proportion of patients whose total score of MDS-UPDRS Ⅱ+Ⅲ changed from baseline by less than 3 points
12 weeks
Movement Disorder Society Unified Parkinson's Disease Rating Scale(MDS-UPDRS)Ⅱ+Ⅲ
Time Frame: 24 weeks
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.
24 weeks
Proportion of MDS-UPDRS II+III total score change <3 points
Time Frame: 24 weeks
Proportion of patients whose total score of MDS-UPDRS Ⅱ+Ⅲ changed from baseline by less than 3 points
24 weeks
Movement Disorder Society Unified Parkinson's Disease Rating Scale(MDS-UPDRS) part Ⅰ
Time Frame: 12 weeks and 24 weeks
Assessment of non-motor symptoms of daily life.There are 13 questions, 6 questions in Part 1 A to be completed by the rater and 7 questions in Part 1 B to be completed by the patient.
12 weeks and 24 weeks
Cleveland Constipation Score（ CCS），Rome Ⅲ Diagnostic Criteria for Constipation
Time Frame: 12 weeks and 24 weeks
Constipation improvement was assessed using the Cleveland Constipation Score Change, an 8-question scale with scores ranging from 0 to 30. Evaluate the improvement rate of constipation according to the changes in the proportion of patients who meet the Rome III constipation diagnostic criteria
12 weeks and 24 weeks
Parkinson's Disease Sleep Scale-2 (PDSS-2):
Time Frame: 12 weeks and 24 weeks
Use Parkinson's Disease Sleep Scale-2 (PDSS-2) to assess the patient's sleep improvement. The scale has 15 questions，the higher the score, the worse the sleep.
12 weeks and 24 weeks
Clinical Global Impression-severity of illness
Time Frame: 12 weeks and 24 weeks
Change in scale scores from baseline to assess change in severity of patient's condition
12 weeks and 24 weeks
Clinical Global Impression-global improvement
Time Frame: 12 weeks and 24 weeks
Evaluate the efficacy of patients based on their current condition compared to the time of enrollment
12 weeks and 24 weeks
Long-term medication safety
Time Frame: 12 weeks and 24 weeks
Compare the incidence of adverse reactions between the two groups
12 weeks and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Friendship Hospital

Investigators

  • Principal Investigator: Houzhen Tuo, PhD, Beijing Friendship Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 11, 2021

Primary Completion (Anticipated)

October 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

April 29, 2021

First Submitted That Met QC Criteria

April 29, 2021

First Posted (Actual)

May 4, 2021

Study Record Updates

Last Update Posted (Estimate)

February 20, 2023

Last Update Submitted That Met QC Criteria

February 17, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019-P2-153-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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