Evaluating the Synergism of Soluble Dietary Fiber With Fecal Microbiota Transplantation in Slow Transit Constipation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the synergism of Soluble Dietary Fiber with Fecal Microbiota Transplantation in Adult Patients with Slow Transit Constipation.

Detailed Description
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Constipation is a chronic disease estimated to affect about 10% - 15% of the worldwide general population. Recent evidence in the literature and collected in our laboratory confirm that constipation can be a consequence of intestinal dysbiosis, which may affect the motility and metabolic environment of colon. Fecal Microbiota Transplantation (FMT) is temporarily effective for patients with slow transit constipation. However, the transplanted microflora cannot maintain for a long time. Along with the gut microbiota returning to the original state, the symptoms relapse. Pectin is a kind of soluble dietary fiber, producing short chain fatty acids (SCFAs) after a series of fermentation by gut flora to supply the energy for epithelial cells, regulate intestinal PH, promote intestinal motility and join effort in immune regulation with intestinal lymphoid tissue. Therefore, we conceive that pectin could promote the colonization of probiotics and reduce adhesion of pathogens.

Official Title
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A Randomized, Controlled Study of Synergism of Soluble Dietary Fiber With Fecal Microbiota Transplantation in Adult Patients With Slow Transit Constipation

Conditions
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Slow Transit Constipation

Intervention / Treatment
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* Drug: Pectin
* Other: Placebo
* Procedure: Fecal microbiota transplantation (FMT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic constipation according to Rome III criteria, defined as two or fewer spontaneous, complete bowel movements (SCBMs) per week for a minimum of 6 months; Age ≥ 18 years; BMI: 18.5-25 kg/m2; Slow colonic transit confirmed by colonic transit test (colonic transit time (CTT) > 48 hours); Normal anorectal manometry, with no evidence of dyssynergia and confirmed ability to expel rectal balloon; No radiographic evidence of functional (i.e. pelvic floor dyssynergia) or anatomical (i.e. significant rectocele and intussusception) impediment to the expulsion of the radio-opaque contrast; Disease duration > 1 year; Traditional treatment with dietary modification, laxatives (including osmotic and stimulant laxatives), and biofeedback tried over the past 6 months without success; Exclusion Criteria: Bowel constipation due to innate factor (i.e. megacolon) or secondary interventions (i.e. drugs, endocrine, metabolic, neurologic or psychologic disorders); History or evidence of gastrointestinal diseases (i.e. obstruction, cancer, inflammatory bowel diseases) ; Previous abdominal surgery, except cholecystectomy, appendicectomy, tubal ligation and cesarean section; Previous proctological or perianal surgery; A constipation condition meeting the Rome III criteria for IBS or functional abdominal pain syndrome; Pregnant or breast-feeding women; Infection with enteric pathogen; Usage of probiotics, prebiotics and/or synbiotics within the last month; Usage of antibiotics and/or PPIs within the last 3 months; Smoking or alcohol addiction within the last 3 months; Uncontrolled hepatic, renal, cardiovascular, respiratory or psychiatric disease; Disease or therapy with drugs (i.e. antidepressants, opioid narcotic analgesics, anticholinergics, calcium antagonists, nitrates, antimuscarinics) that, in the opinion of the investigator, could affect intestinal transit and microbiota.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: FMT + Placebo<br>Patients allocated to control group will receive standard FMT, followed by placebo for 12 weeks. | Other: Placebo<br>* Patients allocated to experiment group will receive 12 g maltodextrin each day for 12 weeks.<br>Procedure: Fecal microbiota transplantation (FMT)<br>* Standardized Frozen Fecal Microbiota will be infused via nasointestinal tube.<br>* Other names: Fecal bacteriotherapy;|
| Experimental: FMT + Pectin<br>Patients allocated to experiment group will receive standard FMT, followed by 24g pectin each day for 12 weeks. | Drug: Pectin<br>* Patients allocated to experiment group will receive 12 g pectin each day for 12 weeks.<br>* Other names: soluble dietary fiber;Procedure: Fecal microbiota transplantation (FMT)<br>* Standardized Frozen Fecal Microbiota will be infused via nasointestinal tube.<br>* Other names: Fecal bacteriotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients having on average three or more SCBMs/week | Proportion of patients having on average three or more spontaneous, complete bowel movements (SCBMs) per week was evaluated at week 4 and 12. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bowel habit assessments | Patients kept daily diaries about times of bowel movements each day, stool consistency, degree of straining severity during defecation, and degree of sensation of incompleteness of evacuation. | 12 weeks | 
| Constipation-related symptoms assessments | Constipation-related symptoms were evaluated using the validated Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire at week 4 and 12. | 12 weeks | 
| Quality-of-Life assessments | Quality-of-Life was evaluated using the validated Patient Assessment of Constipation Quality of Life (PACQOL) self-report questionnaire at week 4 and 12. | 12 weeks | 
| Colonic transit time measurements | Colonic transit time (CTT) was measured at week 4 and 12 with the Metcalf method. | 12 weeks | 
| Usage of laxatives or enemas as rescue medication | If patients did not have a bowel movement for 3 or more consecutive days, they were permitted to take up to 20 g of Macrogol 4000 powder (Forlax). If ineffective, enema were used. Patients kept daily diaries about the rescue medication when used. | 12 weeks | 
| Adverse events | Adverse events include fever, diarrhea, abdominal pain, increased bloating, borborygmi, flatulence, nausea, vomiting, nasopharyngitis, and any other disorders. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fecal Microbiota Transplantation, Soluble Dietary Fiber, Slow Transit Constipation