Efficacy and Safety of Fecal Microbiota Transplantation for Slow Transit Constipation

A Randomized Controlled Study of Efficacy, Safety and Durability of Fecal Microbiota Transplantation in Adult Patients With Slow Transit Constipation

The purpose of this study is to evaluate the effect of fecal microbiota transplantation in adults with slow transit constipation.

Study Overview

• Status: Unknown
• Conditions: Slow Transit Constipation
• Intervention / Treatment: Drug: Fecal microbiota transplantation (FMT); Behavioral: Conventional treatment

Detailed Description

Constipation is a chronic disease estimated to affect about 10% - 15% of the worldwide general population. Constipation frequency appears to augment with increasing age, particularly after 65 years old.

Recent evidence in the literature and collected in the investigators' laboratory confirm that constipation can be a consequence of intestinal dysbiosis, with an increase of potentially pathogenic microorganisms and a decrease of potentially beneficial microorganisms. These alterations may affect the motility and metabolic environment of colon, especially the production of short chain fatty acids (SCFAs).

A new and under-explored method to manipulate the gastrointestinal microbiota involves fecal microbiota transplantation (FMT). There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections (e.g. CDI) and other extraintestinal conditions (e.g. IBD). Similarly, the investigators suppose that reshaping the gut microbiome with FMT would be effective for patients with slow transit constipation.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Recruiting
      • Department of Generay Surgery, Jinling hosptal, Medical School of Nanjing University

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:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fecal microbiota transplantation (FMT); On day 1-6, patients received 100ml fresh FMT by nasointestinal tube, once per day. The nasointestinal tube was placed in the patient's proximal jejunum through endoscopy. Then, donor fecal microbiota was infused within 5 minutes through nasointestinal tube.	Drug: Fecal microbiota transplantation (FMT); Standardized Frozen Fecal Microbiota will be infused via nasointestinal tube.; Other Names: Fecal bacteriotherapy; Behavioral: Conventional treatment; Conventional treatment was taken by both of two groups. 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®, Ipsen, Paris, France). If ineffective, an enema could be used.
Experimental: Conventional treatment; Conventional treatment was taken by both of two groups. 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®, Ipsen, Paris, France). If ineffective, an enema could be used.	Drug: Fecal microbiota transplantation (FMT); Standardized Frozen Fecal Microbiota will be infused via nasointestinal tube.; Other Names: Fecal bacteriotherapy; Behavioral: Conventional treatment; Conventional treatment was taken by both of two groups. 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®, Ipsen, Paris, France). If ineffective, an enema could be used.

What is the study measuring?

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.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean number of bowel movements per week	Patients kept daily diaries about times of bowel movements each day.	3 months
Characteristics of bowel movements	Patients kept daily diaries about stool consistency and degree of straining severity during defecation.	3 months
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.	3 months
Quality-of-Life assessments	Quality-of-Life was evaluated using the validated Patient Assessment of Constipation Quality of Life (PAC-QOL) self-report questionnaire at week 4 and 12.	3 months
Colonic transit time measurements	Colonic transit time (CTT) was measured at week 4 and 12 with the Metcalf method.	3 months
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 was used. Patients kept daily diaries about the rescue medication when used.	3 months
Adverse events	Adverse events include fever, diarrhea, abdominal pain, increased bloating, borborygmi, flatulence, nausea, vomiting, nasopharyngitis, and any other disorders.	3 months

Collaborators and Investigators

• Sponsor: Jinling Hospital, China

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: August 14, 2015
• First Submitted That Met QC Criteria: August 15, 2015
• First Posted (Estimate): August 18, 2015

Study Record Updates

• Last Update Posted (Estimate): November 4, 2016
• Last Update Submitted That Met QC Criteria: November 3, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation; Randomized Controlled Trial; Slow Transit Constipation
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation
• Other Study ID Numbers: RCT-FMT-STC-2015