Evaluation of the Efficacy and Safety of Fecal Microbiota Transplantation for Constipation in Parkinson's Disease

Evaluation of the Efficacy and Safety of Fecal Microbiota Transplantation for Parkinson's Disease Patients With Constipation

Participants will be allocated to FMT group or placebo group at a 1:1 ratio. For interventional group, patients will be given six FMT capsules twice a week for 24 weeks. Placebo capsules are identical in appearance and smell but contain milk powder. At each follow-up visits, participants complete specific scales to assess improvement in constipation, emotion and quality of life. Besides, fecal samples are collected for metagenomics and metabolomics sequencing and blood samples are tested peripheral concentration of levodopa.

Study Overview

• Status: Not yet recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Healthy donor-derived FMT capsule; Drug: Placebo capsule

Detailed Description

This prospective, double-blind, randomised, placebo-controlled study aims to evaluate efficacy and safety of fecal microbiota transplantation for constipation in Parkinson's disease. Participants will be given either FMT capsules or placebo capsules at a ratio of 1:1. For experimental group, patients will be given six FMT capsules twice a week for 24 weeks. Placebo capsules are identical in appearance and smell but contain milk powder. After 24-week treatment, participants complete specific scales to assess improvement in constipation, other PD symptoms, emotion and quality of life. Besides, fecal samples are collected for metagenomics and metabolomics sequencing and blood samples are tested peripheral concentration of levodopa.

• Study Type: Interventional
• Enrollment (Estimated): 76
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shengdi Wu; Phone Number: (86)13817923359; Email: wu.shengdi@zs-hospital.sh.cn
• Study Contact Backup: Name: Xinyi Liu; Email: liu.xinyi2@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • 180 Fenglin Road
      • Contact: Shengdi Wu; Phone Number: (86)13817923359; Email: wu.shengdi@zs-hospital.sh.cn
      • Principal Investigator: Shengdi Wu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participants who fulfill Chinese diagnostic criteria for PD (2016 edition), aged 40-75 years;
2. PD Hoehn-Yahr stage 1-3
3. Participants who have at least 2 of the following symptoms in the past 3 months and the symptoms have been present for at least 6 months: ① More than 25% of defecations are laborious; ② More than 25% of defecations consist of hard or lumpy stools; ③ More than 25% of defecations are accompanied by a sensation of incomplete evacuation; ④ More than 25% of defecations are accompanied by a sensation of anorectal obstruction; ⑤ More than 25% of defecations require manual assistance; ⑥ Less than 3 spontaneous bowel movements per week.
4. Have taken a stable dose of anti-Parkinson drugs, antidepressants and antipsychotics for at least 1 month;
5. Absence of red flags such as weight loss, hematochezia and exclusion of other diagnosis;
6. Have signed the informed consent and agree to participate in this study;

Exclusion Criteria:

1. Parkinsonism-plus syndrome;
2. Stroke, brain trauma or epilepsy;
3. Have undergone surgery intervention due to PD;
4. Pregnant, planning pregnancy or lactating;
5. Psychiatric disorder or unable to cooperate with treatment and follow-up visit;
6. Immunodeficiency or treatment with immune-modulating medication;
7. Have undergone any abdominal surgery, with the exception of appendectomy, cholecystectomy, caesarean section and hysterectomy;
8. Presence of uncontrolled diabetes, hypertension, thyroid disease or other systemic disease;
9. Use of probiotics or antibiotics within 1 month prior to study entry;
10. Presence of severe diseases related to heart, brain, kidney and lung or concomitant malignancies;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FMT capsule group; Participants will be given 6 FMT capsules twice a week for 24 weeks. The FMT capsules derived from healthy donors.	Drug: Healthy donor-derived FMT capsule; Participants will be treated with healthy donor-derived fecal microbiota transplantation in the form of oral capsules.
Placebo Comparator: Placebo capsule group; Participants will be given 6 placebo capsules twice a week for 24 weeks. Placebo capsules are identical in appearance and smell as FMT capsules but contain milk powder.	Drug: Placebo capsule; Capsules whose appearance and smell are identical as FMT capsules but contain milk powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate of constipation in Parkinson's Disease (PD)	Efficacy index is calculated based on Wexner score. Efficacy index ≥30% is defined as response.	at week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline PD symptoms at week 5, week 13 and week 24	PD symptoms are assessed via Unified Parkinson's Disease Rating Scale (UPDRS), PD Hoehn-Yahr grade, Non-Motor Symptoms Questionnaire (NMSQ). Change in PD symptoms is obtained by evaluating theses scales at baseline and week 5, week 13 and week 24.	at baseline and week 5, week 13 and week 24
Change from baseline anxiety at week 5, week 13 and week 24	Self-rating Anxiety Scale (SAS) is used to evaluate anxiety in PD patients, with a score ranging from 25 to 100. Higher score indicates higher level of anxiety. Change in SAS score is obtained by evaluating the scale at baseline, week 5, week 13 and week 24.	at baseline and week 5, week 13 and week 24
Change from baseline depression at week 5, week 13 and week 24	Self-rating Depression Scale (SDS) is used to evaluate depression in PD patients, with a score ranging from 25 to 100. Higher score indicates higher level of depression. Change in SDS score is obtained by evaluating the scale at baseline, week 5, week 13 and week 24.	at baseline and week 5, week 13 and week 24
Change from baseline quality of life at week 5, week 13 and week 24	Parkinson's disease Questionnaire (PDQ-39) is used to assess quality of life in PD patients. Higher score indicates worse life quality. Change in PDQ-39 score is obtained by evaluating the scale at baseline, week 5, week 13 and week 24.	at baseline and week 5, week 13 and week 24
Change from baseline drug concentration of levodopa in peripheral blood at week 13 and week 24	Blood samples are collected and tested for drug concentration of levodopa in peripheral blood	at baseline, week 13 and week 24
Change from baseline fecal microbiota based on metagenomics sequencing at week 5, week 13 and week 24	Fecal samples are collected at baseline, week 5, week 13 and week 24. Change in fecal microbiota is measured by metagenomics.	at baseline, week 5, week 13 and week 24
Change from baseline fecal metabolites based on non-targeted metabolomics at week 5, week 13 and week 24	Fecal samples are collected at baseline, week 5, week 13 and week 24. Change in fecal metabolites is measured by non-targeted metabolomics.	at baseline, week 5, week 13 and week 24

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Shengdi Wu, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Digestive; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Constipation
• Other Study ID Numbers: B2024-002

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