<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04451096</url>
  </required_header>
  <id_info>
    <org_study_id>FF-2018-387</org_study_id>
    <nct_id>NCT04451096</nct_id>
  </id_info>
  <brief_title>Probiotics-prebiotic Fiber Therapy in Parkinson's Disease Patients With Constipation</brief_title>
  <official_title>Probiotics-prebiotic Fiber Therapy Improved Bowel Opening Frequency and Whole Gut Transit Time in Parkinson's Disease Patients With Constipation: A Randomised Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National University of Malaysia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National University of Malaysia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A double blinded randomised placebo controlled trial to evaluate the efficacy of probiotics&#xD;
      on constipation symptoms and whole gut transit time in patients with Parkinson's disease.PD&#xD;
      patients with constipation were randomized to receive a multi-strain probiotic (Lactobacillus&#xD;
      spp and Bifidobacterium spp at 30 X 109 CFU) with fructo-oligosaccaride (FOS) or placebo&#xD;
      (fermented milk) twice daily for 8 weeks. Primary outcomes include changes in the presence of&#xD;
      constipation symptoms using 9 items of Garrigues Questionnaire (GQ), which included an item&#xD;
      on bowel opening frequency. Secondary and exploratory outcomes include whole gut transit time&#xD;
      (WGTT), quality of life (PDQ39-SI), motor (MDS-UPDRS) and non-motor symptoms (NMSS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was an eight-week double-blind, randomized placebo-controlled intervention study&#xD;
      involving 55 idiopathic PD patients attending tertiary hospital. This study was conducted in&#xD;
      accordance with good clinical practice as per Declaration of Helsinki and was approved by the&#xD;
      institution's Research and Ethics Committee (FF-2018-387). Written informed consent was&#xD;
      obtained from all particpants prior to enrollment.&#xD;
&#xD;
      Participants were included if they were aged 18 or older; were diagnosed with idiopathic PD&#xD;
      in Hoehn and Yahr stages 1-4, and fulfilled the Rome III criteria for functional constipation&#xD;
      which requires the presence of recurrent abdominal pain 3 days per month in the last 3&#xD;
      months, and symptom onset 6 months prior to diagnosis, with additional criteria below to be&#xD;
      fulfilled, as adapted from Longstreth, et al12.&#xD;
&#xD;
        1. Must include two or more of the following:&#xD;
&#xD;
             1. Straining during at least 25% of defecations&#xD;
&#xD;
             2. Lumpy or hard stools in at least 25% of defecations&#xD;
&#xD;
             3. Sensation of incomplete evacuation for at least 25% of defecations d. Sensation of&#xD;
                anorectal obstruction/blockage for at least 25% of defecations&#xD;
&#xD;
           e. Manual maneuvers to facilitate at least 25% of defecations (e.g, digital evacuation,&#xD;
           support of the pelvic floor) f. Fewer than 3 defecations per week&#xD;
&#xD;
        2. Loose stools are rarely present without the use of laxatives&#xD;
&#xD;
        3. There are insufficient criteria for IBS&#xD;
&#xD;
      Participants were excluded if they had: a MMSE score of ≤ 21/30; a positive stool occult&#xD;
      blood screening; a diagnosis of secondary parkinsonism; previous history of small and large&#xD;
      bowel disease; prior history of gastrointestinal tract surgery; use of probiotics or&#xD;
      antibiotics two weeks prior to baseline visit; been on medications such as antidepressants or&#xD;
      anticholinergics; history of lactose intolerance; concomitant diagnosis of hypothyroidism and&#xD;
      diabetes mellitus.&#xD;
&#xD;
      All participants were assessed at baseline and at 8 weeks following intervention for all&#xD;
      outcome assessments. At baseline, additional data on demographics (age, sex, educational&#xD;
      level), duration of PD, dopaminergic medication, Hoehn &amp; Yahr Scoring during ON period, and&#xD;
      the level of physical activity were recorded at baseline. A sedentary behaviour was defined&#xD;
      as being physically active &lt; 4 hours /week.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 6, 2018</start_date>
  <completion_date type="Actual">February 28, 2019</completion_date>
  <primary_completion_date type="Actual">February 28, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>placebo controlled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>double blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>constipation symptoms</measure>
    <time_frame>8 weeks</time_frame>
    <description>The presence of constipation symptoms at baseline and at 8 weeks evaluated by&#xD;
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 &gt;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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Whole Gut Transit Time (WGTT) in hours</measure>
    <time_frame>8 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of patients with constipation (Bowel motion &lt; 3 per week) in percentage</measure>
    <time_frame>8 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Movement Disorders Society- Unified Parkinson's Disease Rating Scale Part 11</measure>
    <time_frame>8 weeks</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Movement Disorders Society- Unified Parkinson's Disease Rating Scale Part 111</measure>
    <time_frame>8 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non motor symptom score</measure>
    <time_frame>8 weeks</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parkinsons Disease Quality of Life -39 Summary Index (PDQ39SI)</measure>
    <time_frame>8 weeks</time_frame>
    <description>Change in PD9 39-SI which measure 8 domains of Quality of Life ( Lower score indicates better quality of life)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight in kilogram</measure>
    <time_frame>8 weeks</time_frame>
    <description>Change in body weight measurement in Kg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Height in metres</measure>
    <time_frame>Baseline</time_frame>
    <description>Height will be measured in meters at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Mass Index (kg/m2)</measure>
    <time_frame>8 weeks</time_frame>
    <description>Weight and height will be combined to report BMI in kg/m^</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Parkinson Disease</condition>
  <condition>Constipation</condition>
  <arm_group>
    <arm_group_label>Probiotic with prebiotic</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: Probiotic sachet containing granulated multiple strains of Lactobacillus and Bifidobacterium, granulated fermented milk, lactose, fructo-oligosaccharide (FOS) with orange flavouring.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Drug : Placebo sachet of granulated milk, lactose and orange flavouring, without FOS or microbial cells which appeared similar to the probiotics</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Probiotics with prebiotic</intervention_name>
    <description>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</description>
    <arm_group_label>Probiotic with prebiotic</arm_group_label>
    <other_name>Multistrain Probiotics with prebiotic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>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</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Granulated milk products</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 or older; were diagnosed with idiopathic PD&#xD;
&#xD;
          -  PD with Hoehn and Yahr stages 1-4,&#xD;
&#xD;
          -  Fulfilled the Rome III criteria for functional constipation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  MMSE score of ≤ 21/30&#xD;
&#xD;
          -  Positive stool occult blood screening&#xD;
&#xD;
          -  Diagnosis of secondary parkinsonism&#xD;
&#xD;
          -  Previous history of small and large bowel disease&#xD;
&#xD;
          -  History of gastrointestinal tract surgery&#xD;
&#xD;
          -  Use of probiotics or antibiotics two weeks prior to baseline visit&#xD;
&#xD;
          -  Been on medications such as antidepressants or anticholinergics&#xD;
&#xD;
          -  History of lactose intolerance&#xD;
&#xD;
          -  Concomitant diagnosis of hypothyroidism and diabetes mellitus.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Norlinah Mohamed Ibrahim, MBBChMRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>National University of Malaysia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Canselor Tuanku Muhriz, UKM Medical Center</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>56000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Malaysia</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>June 25, 2020</last_update_submitted>
  <last_update_submitted_qc>June 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National University of Malaysia</investigator_affiliation>
    <investigator_full_name>Dr Norlinah Mohamed Ibrahim</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Parkinson's disease</keyword>
  <keyword>Constipation</keyword>
  <keyword>Probiotics</keyword>
  <keyword>Prebiotic</keyword>
  <keyword>Gut transit time</keyword>
  <keyword>Motor outcome</keyword>
  <keyword>NMSS</keyword>
  <keyword>PDQ39</keyword>
  <keyword>Randomised controlled trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Constipation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04451096
org study id: FF-2018-387
nct id: NCT04451096
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
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).
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: placebo controlled
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: double blinded
measure: constipation symptoms
time frame: 8 weeks
description: 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
measure: Whole Gut Transit Time (WGTT) in hours
time frame: 8 weeks
description: 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.
measure: Frequency of patients with constipation (Bowel motion < 3 per week) in percentage
time frame: 8 weeks
description: 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.
measure: Movement Disorders Society- Unified Parkinson's Disease Rating Scale Part 11
time frame: 8 weeks
description: 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
measure: Movement Disorders Society- Unified Parkinson's Disease Rating Scale Part 111
time frame: 8 weeks
description: 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.
measure: Non motor symptom score
time frame: 8 weeks
description: 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
measure: Parkinsons Disease Quality of Life -39 Summary Index (PDQ39SI)
time frame: 8 weeks
description: Change in PD9 39-SI which measure 8 domains of Quality of Life ( Lower score indicates better quality of life)
measure: Weight in kilogram
time frame: 8 weeks
description: Change in body weight measurement in Kg
measure: Height in metres
time frame: Baseline
description: Height will be measured in meters at baseline
measure: Body Mass Index (kg/m2)
time frame: 8 weeks
description: Weight and height will be combined to report BMI in kg/m^
arm group label: Probiotic with prebiotic
arm group type: Active Comparator
description: Drug: Probiotic sachet containing granulated multiple strains of Lactobacillus and Bifidobacterium, granulated fermented milk, lactose, fructo-oligosaccharide (FOS) with orange flavouring.
arm group label: Placebo
arm group type: Placebo Comparator
description: Drug : Placebo sachet of granulated milk, lactose and orange flavouring, without FOS or microbial cells which appeared similar to the probiotics
intervention type: Dietary Supplement
intervention name: Probiotics with prebiotic
description: 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
arm group label: Probiotic with prebiotic
other name: Multistrain Probiotics with prebiotic
intervention type: Dietary Supplement
intervention name: Placebo
description: 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
arm group label: Placebo
other name: Granulated milk products
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Norlinah Mohamed Ibrahim, MBBChMRCP
role: Principal Investigator
affiliation: National University of Malaysia
facility: 
country: Malaysia
responsible party type: Principal Investigator
investigator affiliation: National University of Malaysia
investigator full name: Dr Norlinah Mohamed Ibrahim
investigator title: Professor
mesh term: Parkinson Disease
mesh term: Constipation
sharing ipd: No