Clinical trial NCT04451096: Probiotics-prebiotic Fiber Therapy in Parkinson's Disease Patients With Constipation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson Disease
Constipation
Keywords: Parkinson's disease
Constipation
Probiotics
Prebiotic
Gut transit time
Motor outcome
NMSS
PDQ39
Randomised controlled trial
Lead sponsor: National University of Malaysia
Sponsor class: OTHER
First posted: 2020-06-30
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: placebo controlled
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: constipation symptoms
timeFrame: 8 weeks
Secondary outcomes:
measure: Whole Gut Transit Time (WGTT) in hours
timeFrame: 8 weeks
measure: Frequency of patients with constipation (Bowel motion < 3 per week) in percentage
timeFrame: 8 weeks
measure: Movement Disorders Society- Unified Parkinson's Disease Rating Scale Part 11
timeFrame: 8 weeks
measure: Movement Disorders Society- Unified Parkinson's Disease Rating Scale Part 111
timeFrame: 8 weeks
measure: Non motor symptom score
timeFrame: 8 weeks
measure: Parkinsons Disease Quality of Life -39 Summary Index (PDQ39SI)
timeFrame: 8 weeks
measure: Weight in kilogram
timeFrame: 8 weeks
measure: Height in metres
timeFrame: Baseline
measure: Body Mass Index (kg/m2)
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Kuala Lumpur
country: Malaysia
facility: Hospital Canselor Tuanku Muhriz, UKM Medical Center
Study officials:
affiliation: National University of Malaysia
name: Norlinah Mohamed Ibrahim, MBBChMRCP
role: PRINCIPAL_INVESTIGATOR
References: