Probiotics-prebiotic Fiber Therapy in Parkinson's Disease Patients With Constipation

Probiotics-prebiotic Fiber Therapy Improved Bowel Opening Frequency and Whole Gut Transit Time in Parkinson's Disease Patients With Constipation: A Randomised Controlled Study

A double blinded randomised placebo controlled trial to evaluate the efficacy of probiotics on constipation symptoms and whole gut transit time in patients with Parkinson's disease.PD patients with constipation were randomized to receive a multi-strain probiotic (Lactobacillus spp and Bifidobacterium spp at 30 X 109 CFU) with fructo-oligosaccaride (FOS) or placebo (fermented milk) twice daily for 8 weeks. Primary outcomes include changes in the presence of constipation symptoms using 9 items of Garrigues Questionnaire (GQ), which included an item on bowel opening frequency. Secondary and exploratory outcomes include whole gut transit time (WGTT), quality of life (PDQ39-SI), motor (MDS-UPDRS) and non-motor symptoms (NMSS).

Study Overview

• Status: Completed
• Conditions: Parkinson Disease; Constipation
• Intervention / Treatment: Dietary supplement: Probiotics with prebiotic; Dietary supplement: Placebo

Detailed Description

This was an eight-week double-blind, randomized placebo-controlled intervention study involving 55 idiopathic PD patients attending tertiary hospital. This study was conducted in accordance with good clinical practice as per Declaration of Helsinki and was approved by the institution's Research and Ethics Committee (FF-2018-387). Written informed consent was obtained from all particpants prior to enrollment.

Participants were included if they were aged 18 or older; were diagnosed with idiopathic PD in Hoehn and Yahr stages 1-4, and fulfilled the Rome III criteria for functional constipation which requires the presence of recurrent abdominal pain 3 days per month in the last 3 months, and symptom onset 6 months prior to diagnosis, with additional criteria below to be fulfilled, as adapted from Longstreth, et al12.

1. Must include two or more of the following:

   1. Straining during at least 25% of defecations
   2. Lumpy or hard stools in at least 25% of defecations
   3. Sensation of incomplete evacuation for at least 25% of defecations d. Sensation of anorectal obstruction/blockage for at least 25% of defecations

   e. Manual maneuvers to facilitate at least 25% of defecations (e.g, digital evacuation, support of the pelvic floor) f. Fewer than 3 defecations per week

2. Loose stools are rarely present without the use of laxatives
3. There are insufficient criteria for IBS

Participants were excluded if they had: a MMSE score of ≤ 21/30; a positive stool occult blood screening; a diagnosis of secondary parkinsonism; previous history of small and large bowel disease; prior history of gastrointestinal tract surgery; use of probiotics or antibiotics two weeks prior to baseline visit; been on medications such as antidepressants or anticholinergics; history of lactose intolerance; concomitant diagnosis of hypothyroidism and diabetes mellitus.

All participants were assessed at baseline and at 8 weeks following intervention for all outcome assessments. At baseline, additional data on demographics (age, sex, educational level), duration of PD, dopaminergic medication, Hoehn & Yahr Scoring during ON period, and the level of physical activity were recorded at baseline. A sedentary behaviour was defined as being physically active < 4 hours /week.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 3

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 56000
    • Hospital Canselor Tuanku Muhriz, UKM Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 or older; were diagnosed with idiopathic PD
• PD with Hoehn and Yahr stages 1-4,
• Fulfilled the Rome III criteria for functional constipation

Exclusion Criteria:

• MMSE score of ≤ 21/30
• Positive stool occult blood screening
• Diagnosis of secondary parkinsonism
• Previous history of small and large bowel disease
• History of gastrointestinal tract surgery
• Use of probiotics or antibiotics two weeks prior to baseline visit
• Been on medications such as antidepressants or anticholinergics
• History of lactose intolerance
• Concomitant diagnosis of hypothyroidism and diabetes mellitus.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Probiotic with prebiotic; Drug: Probiotic sachet containing granulated multiple strains of Lactobacillus and Bifidobacterium, granulated fermented milk, lactose, fructo-oligosaccharide (FOS) with orange flavouring.	Dietary supplement: Probiotics with prebiotic; Patients were instructed to consume one sachet twice daily mixed with a glass of water, before or after meals, for a duration of 8 weeks; Other Names: Multistrain Probiotics with prebiotic
Placebo Comparator: Placebo; Drug : Placebo sachet of granulated milk, lactose and orange flavouring, without FOS or microbial cells which appeared similar to the probiotics	Dietary supplement: Placebo; Patients were instructed to consume one sachet twice daily mixed with a glass of water, before or after meals, for a duration of 8 weeks; Other Names: Granulated milk products

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
constipation symptoms	The presence of constipation symptoms at baseline and at 8 weeks evaluated by Garrigues Questionnaire (GQ).GQ is a 21-item self-reported screening questionnaire to detect the presence of constipation symptoms, using two different sets of four-point Likert scale responses.Although 12 items assess bowel habits, 9 items specifically assess constipation symptoms and were used in our evaluation: (i)Feeling of blockage in the anus;(ii) Need to press around anus/vagina to complete bowel movement; (iii) Spend >10 minutes to pass stool;(iv) Straining during bowel movement;(v) Feeling of hard stool;(vi) Feeling of incomplete emptying sensation; (vii)Bowel opening frequency;(viii) Frequency of oral laxative use;(ix) Frequency of enema use	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole Gut Transit Time (WGTT) in hours	WGTT was measured at baseline and at the end of 8 weeks, using red carmine capsule. The mean change in the WGTT (WGTT 8 weeks - WGTT baseline) was compared between the two groups.	8 weeks
Frequency of patients with constipation (Bowel motion < 3 per week) in percentage	Based on the stool diary, the percentage of patients who experienced less than 3 BM per week was calculated at baseline and at the end of study.	8 weeks
Movement Disorders Society- Unified Parkinson's Disease Rating Scale Part 11	This measures the motor aspects of activity of daily living and consists of 13 items with scores between 0- 52. This instrument is given at baseline and 8 weeks. Lower score indicates low severity	8 weeks
Movement Disorders Society- Unified Parkinson's Disease Rating Scale Part 111	This measures the seveirty of motor symptoms using 18 items (score 0-72). This instrument is given at baseline and 8 weeks. Lower score indicates low severity.	8 weeks
Non motor symptom score	Change in non-motor symptoms severity scores using the Non motor Symptom Scale (NMSS) which consists of 9 domains (cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucination, attention/memory, gastrointestinal tract, urinary, sexual function and miscellaneous.Score ranges from minimum of 3 to 360. Lower score indicates lower severity	8 weeks
Parkinsons Disease Quality of Life -39 Summary Index (PDQ39SI)	Change in PD9 39-SI which measure 8 domains of Quality of Life ( Lower score indicates better quality of life)	8 weeks
Weight in kilogram	Change in body weight measurement in Kg	8 weeks
Height in metres	Height will be measured in meters at baseline	Baseline
Body Mass Index (kg/m2)	Weight and height will be combined to report BMI in kg/m^	8 weeks

Collaborators and Investigators

• Sponsor: National University of Malaysia
• Investigators: Principal Investigator: Norlinah Mohamed Ibrahim, MBBChMRCP, National University of Malaysia

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2018
• Primary Completion (Actual): February 28, 2019
• Study Completion (Actual): February 28, 2019

Study Registration Dates

• First Submitted: June 19, 2020
• First Submitted That Met QC Criteria: June 25, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Actual): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 25, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Constipation; Probiotics; Prebiotic; Randomised controlled trial; Parkinson's disease; Gut transit time; Motor outcome; NMSS; PDQ39
• 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: FF-2018-387

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
• product manufactured in and exported from the U.S.: No