Multistrain Probiotic for Functional Constipation
Primary Purpose
Functional Constipation
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
High dose Multistrain probiotic, 100 billion cfu/day
Low dose Multistrain probiotic, 15 billion cfu/day
Sponsored by
About this trial
This is an interventional supportive care trial for Functional Constipation focused on measuring Constipation, Probiotic, Randomized Controlled Trial
Eligibility Criteria
Inclusion Criteria:
- Age 18 to 65 years
- Body mass index 18.5 to 39.9 kg/m2
Meets the criteria below over the last 3 months with symptom onset at least 6 months prior (Rome III definition of functional constipation 1):
Meets 2 or more of the following criteria:
- Straining during at least 25% of defecations
- Lumpy or hard stools in at least 25% of defecations
- Sensation of incomplete evacuation for at least 25% of defecations
- Sensation of anorectal obstruction/blockage for at least 25% of defecations
- Manual maneuvers to facilitate at least 25% of defecations (e.g. digital evacuation, support of the pelvic floor)
- Fewer than three defecations per week
- Loose stools are rarely present without the use of laxatives
- Insufficient criteria for irritable bowel syndrome
- Agree to use contraception throughout study period, unless postmenopausal or surgically sterile (females only)
- Able to understand the nature and purpose of the study including potential risks and side effects
- Willing to consent to study participation and to comply with study requirements
Successful completion of 2-week run-in period, defined as:
- Must meet the Rome III definition of functional constipation during this 2-week period
- Completion of all study-related questionnaires
Exclusion Criteria:
- Major gastrointestinal complication (e.g. Crohn's disease, ulcer, cancer)
- Prior abdominal surgery that, in the investigator's opinion, may confound study outcomes
- Clinically significant systemic disease (e.g. cancer, diabetes, CAD)
- Consumption of probiotics or prebiotics within 2 weeks of randomization
- Antibiotic use within 4 weeks of randomization
- Laxative or other constipation medication use within 2 weeks of randomization
- Eating disorder
- Known allergies to any substance in the study product, including lactose intolerance
- Pregnant or breastfeeding women
- History of alcohol, drug, or medication abuse
- Participation in another study with any investigational product within 3 months of randomization
- Any condition that could, in the opinion of the investigator, preclude the subject's ability to successfully and safely complete the study or that may confound study outcomes
Sites / Locations
- SprimRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Probiotic, high dose
Probiotic, low dose
Placebo
Arm Description
High dose Multistrain probiotic, 100 billion cfu/day
Low dose Multistrain probiotic, 15 billion cfu/day
Placebo
Outcomes
Primary Outcome Measures
Whole gut transit time
Secondary Outcome Measures
Patient Assessment of Constipation Quality of Life (PAC-QOL)
Wexner Constipation Score (WCS)
Gastrointestinal Symptom Rating Scale (GSRS)
Stool frequency
Stool consistency
Fecal probiotic count
Adverse events
Full Information
NCT ID
NCT01618617
First Posted
June 11, 2012
Last Updated
November 29, 2012
Sponsor
Renew Life Formulas Inc
Collaborators
Sprim Advanced Life Sciences
1. Study Identification
Unique Protocol Identification Number
NCT01618617
Brief Title
Multistrain Probiotic for Functional Constipation
Official Title
Dose-response Effectiveness of 6-week Multistrain Probiotic Supplementation on Whole Gut Transit Time, Quality of Life, and Gastrointestinal Symptoms in Adults With Functional Constipation
Study Type
Interventional
2. Study Status
Record Verification Date
June 2012
Overall Recruitment Status
Unknown status
Study Start Date
June 2012 (undefined)
Primary Completion Date
March 2013 (Anticipated)
Study Completion Date
March 2013 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Renew Life Formulas Inc
Collaborators
Sprim Advanced Life Sciences
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Subjects will be screened and will enter a placebo-only 2-week run-in period during which constipation symptoms will be evaluated and any disallowed products (e.g. probiotics) must be discontinued. Following successful completion of the run-in period, subjects will be randomized to probiotic (high or low-dose groups) or placebo. Subjects will then consume their assigned product daily for 6 weeks. Subjects will undergo abdominal x-rays on study days 0 and 42 to assess transit time with each examination preceded by 6 days of radiopaque Sitz marker ingestion. Subject diaries will be used to collect bowel movement frequency, stool consistency, concomitant medications, and adverse events each day during the trial. Stool samples will be collected at baseline and end of study to assess fecal probiotic count. PAC-QOL, WCS, and GSRS questionnaires will be administered at baseline and day 42. 24-hour food recalls will be administered at day 0 and 42 and the following parameters will be assessed: total calories, carbohydrate, fat, protein, fiber, and liquid intake. Weekly physical activity recalls will be completed.
Detailed Description
Primary Endpoint: Whole gut transit time
The primary endpoint of this clinical trial is whole gut transit time, which will be assessed using abdominal x-rays (supine anteroposterior kidney-ureter-bladder, KUB) on days 0 and 42. Each subject will ingest 24 radiopaque Sitz markers each day for 6 consecutive days at the same time of the day prior to abdominal x-rays on days 0 and 42, also taken at the same time of the day that the markers were taken. The number of markers present in the right, left, and rectosigmoid colon will be summed to yield a total marker count. Whole gut transit time will be calculated using the classic film estimate as described in the following formula:
WGTT = ni x (t/N) 19, 20
where ni is the number of markers observed on x-ray, t is the time between marker ingestions in hours, and N is the total number of markers ingested each day. Thus, in this study, t/N equals 1 (24 markers per capsule/24 hours between marker ingestions), and WGTT is, therefore, equal to the total marker count 19, 20.
Marker counts will be identified by a single radiologist at each site who will remain blinded to subject treatment assignment.
The methodology above is safe, noninvasive, and the two abdominal x-rays required for this study collectively expose each subject to radiation doses of approximately 140 millirem (equivalent to 1.4 millisievert). The overall lifetime risk that this radiation dosage may cause cancer is approximately 1 in 4,000 for women aged 18 years, 1 in 6,000 for men aged 18 years, 1 in 20,000 for women aged 70 years, and 1 in 25,000 for men aged 70 years. Similar abdominal x-ray methodology has been utilized in similar studies in adults aged 18 years and older 21, 22.
Secondary Endpoint: Patient Assessment of Constipation Quality of Life (PAC-QoL) The PAC-QoL (Appendix A) is a 28-question survey that measures the impact that constipation has on daily life over the past 2 weeks. The questions are comprised of four subscales (worries and concerns, physical discomfort, psychosocial discomfort, and satisfaction) and an overall scale. Multinational studies have demonstrated that the PAC-QoL is internally consistent, reproducible, valid, and responsive to improvements over time 23. Subjects will complete the PAC-QoL at days 0 and 42.
Secondary Endpoint: Wexner Constipation Score (WCS) The Wexner Constipation Score (WCS) (Appendix B) is an 8-question survey that assesses frequency of bowel movements, straining, incomplete evacuation, abdominal pain, time needed for defecation, assistance for defecation, unsuccessful attempts, and duration of constipation. The WCS is a validated questionnaire since WCS scores correlate well with objective physiologic findings in constipated patients 24. Subjects will complete the WCS at days 0 and 42.
Secondary Endpoint: Gastrointestinal Symptom Rating Scale (GSRS) The GSRS (Appendix C) is a 15-item instrument designed to assess common GI symptoms 25. It has five subscales (reflux, diarrhea, constipation, indigestion, and abdominal pain) with subscale scores ranging from 1 (no discomfort) to 7 (severe discomfort). Higher scores represent higher symptom burden. Subjects will complete the GSRS at days 0 and 42.
Secondary Endpoint: Stool frequency Throughout the study, subjects will record the number of defecations per day in a diary throughout the study. The stool frequency endpoint will be the absolute change in weekly stools in each group from the second week of the run-in period to the sixth study week.
Secondary Endpoint: Stool Consistency Stool consistency will be rated with the Bristol Stool Scale Form 26 (Appendix D). Subjects will grade each stool using a daily diary throughout the study. The stool consistency endpoint will be the mean change in each group from the second week of the run-in period to the sixth study week.
Secondary Endpoint: Fecal Probiotic Count Stool samples will be collected at baseline and end of study to assess fecal probiotic count via live culture, which will include total lactobacillis count and total bifidobacterium count. At the Day 0 visit following randomization, subjects will be provided two separate stool collection kits-one to be used at baseline and one to be used at the end of the supplementation period.
After receipt of the kits, subjects must provide the first stool sample before taking the first dose of study product, regardless of the length of time needed to have a bowel movement. The stool sample can be provided at the study site on Day 0 or the subject may collect their first stool thereafter and ship the sample in a provided refrigerated container to the laboratory for analysis. Once the first stool sample is provided, the subject may then begin consuming study product.
During the final 3 days of the supplementation period (i.e. Day 40, 41, or 42), subjects must provide another stool sample and ship the sample in a provided refrigerated container to the laboratory for analysis. This must be completed before returning to the site for the Day 42 assessments.
Secondary Endpoint: Adverse Events Adverse events (AEs) will be assessed throughout this clinical study. The main safety endpoint will be the proportion of subjects in each group that report one of more AEs at any time during the study. Please see Section 6 for additional details on the AE assessment.
Ancillary Outcome: International Physical Activity Questionnaire (IPAQ)-short version The International Physical Activity Questionnaire (IPAQ)-short version is a validated questionnaire suitable for quantifying physical activity levels in adults (Appendix E) 27.
Ancillary Outcome: 24-hour Food Recall A 24-hour food recall will be completed in order to quantify total calories, carbohydrate (g), fat (g), protein (g), fiber (g), and liquid intake (ml). The food recall must take place on a weekday (Monday through Thursday). Subjects must record all foods and beverages consumed as well as the quantity of each (recorded as weight or volume).
Ancillary Outcome: Concomitant medication use Throughout the study, subjects will record use of any concomitant medication and, if required, the need for rescue medication each day in a diary.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Functional Constipation
Keywords
Constipation, Probiotic, Randomized Controlled Trial
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
81 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Probiotic, high dose
Arm Type
Experimental
Arm Description
High dose Multistrain probiotic, 100 billion cfu/day
Arm Title
Probiotic, low dose
Arm Type
Experimental
Arm Description
Low dose Multistrain probiotic, 15 billion cfu/day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Dietary Supplement
Intervention Name(s)
High dose Multistrain probiotic, 100 billion cfu/day
Other Intervention Name(s)
Ultimate Flora Critical
Intervention Description
100 billion cfu live bacteria (60 billion cfu bifidobacterium cultures and 40 billion lactobacillus cultures).
Intervention Type
Dietary Supplement
Intervention Name(s)
Low dose Multistrain probiotic, 15 billion cfu/day
Other Intervention Name(s)
Ultimate Flora Critical Care capsules
Intervention Description
15 billion cfu live bacteria (9 billion cfu bifidobacterium cultures and 6 billion lactobacillus cultures).
Primary Outcome Measure Information:
Title
Whole gut transit time
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Patient Assessment of Constipation Quality of Life (PAC-QOL)
Time Frame
6 weeks
Title
Wexner Constipation Score (WCS)
Time Frame
6 weeks
Title
Gastrointestinal Symptom Rating Scale (GSRS)
Time Frame
6 weeks
Title
Stool frequency
Time Frame
6 weeks
Title
Stool consistency
Time Frame
6 weeks
Title
Fecal probiotic count
Time Frame
6 weeks
Title
Adverse events
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age 18 to 65 years
Body mass index 18.5 to 39.9 kg/m2
Meets the criteria below over the last 3 months with symptom onset at least 6 months prior (Rome III definition of functional constipation 1):
Meets 2 or more of the following criteria:
Straining during at least 25% of defecations
Lumpy or hard stools in at least 25% of defecations
Sensation of incomplete evacuation for at least 25% of defecations
Sensation of anorectal obstruction/blockage for at least 25% of defecations
Manual maneuvers to facilitate at least 25% of defecations (e.g. digital evacuation, support of the pelvic floor)
Fewer than three defecations per week
Loose stools are rarely present without the use of laxatives
Insufficient criteria for irritable bowel syndrome
Agree to use contraception throughout study period, unless postmenopausal or surgically sterile (females only)
Able to understand the nature and purpose of the study including potential risks and side effects
Willing to consent to study participation and to comply with study requirements
Successful completion of 2-week run-in period, defined as:
Must meet the Rome III definition of functional constipation during this 2-week period
Completion of all study-related questionnaires
Exclusion Criteria:
Major gastrointestinal complication (e.g. Crohn's disease, ulcer, cancer)
Prior abdominal surgery that, in the investigator's opinion, may confound study outcomes
Clinically significant systemic disease (e.g. cancer, diabetes, CAD)
Consumption of probiotics or prebiotics within 2 weeks of randomization
Antibiotic use within 4 weeks of randomization
Laxative or other constipation medication use within 2 weeks of randomization
Eating disorder
Known allergies to any substance in the study product, including lactose intolerance
Pregnant or breastfeeding women
History of alcohol, drug, or medication abuse
Participation in another study with any investigational product within 3 months of randomization
Any condition that could, in the opinion of the investigator, preclude the subject's ability to successfully and safely complete the study or that may confound study outcomes
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karen Cravotto
Phone
415.291.2020
Email
karen.cravotto@sprim.com
First Name & Middle Initial & Last Name or Official Title & Degree
Heather McLaughlin
Phone
415.291.2020
Email
heather.mclaughlin@sprim.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
JoAnn Hattner, MPH, RD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sprim
City
San Francisco
State/Province
California
ZIP/Postal Code
94109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth von Dollen
Phone
415-722-0234
Email
elizabeth.vondollen@sprim.com
First Name & Middle Initial & Last Name & Degree
JoAnn Hattner, MPH, RD
12. IPD Sharing Statement
Learn more about this trial
Multistrain Probiotic for Functional Constipation
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