Constipation
Conditions
Keywords
constipation, probiotic, functional constipation, IBS-C
Brief summary
This study will investigate the effects of 4-week probiotic supplementation on whole gut transit time and gastrointestinal symptoms in adults with functional constipation.
Detailed description
This prospective, double-blind, randomized, placebo-controlled clinical trial will investigate the effects of 4-week B. lactis HN019 supplementation on whole gut transit time and gastrointestinal symptoms in adults with functional constipation. Participants who meet all study entry criteria will enter a 2-week run-in period. Following successful completion of the run-in period, subjects will be randomized to 4-week supplementation with B. lactis HN019 (10 billion cfu), B. lactis HN019 (1 billion cfu), or placebo. The primary outcome of whole gut transit time will be evaluated with abdominal x-rays on days 0 and 28. Secondary outcomes include IBS-specific questionnaires (administered on days 0 and 28); abdominal pain severity, bowel movement frequency, stool consistency, and adverse events (evaluated daily throughout the study); and overall product satisfaction (evaluated at day 28). Physical activity questionnaires and 24-hour food recalls will be completed periodically during the trial.
Interventions
DIETARY_SUPPLEMENTB. lactis HN019
Capsule containing 10 billion cfu B. lactis HN019 once a day
DIETARY_SUPPLEMENTPlacebo
Capsule containing no probiotic once a day
Sponsors
DuPont Nutrition and Health
Fonterra Research Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 70 years * Body mass index between 18.5 and 34.9 kg/m2 * Self-reported unsatisfactory defecation due to infrequent stools and/or difficult stool passage, which includes at least one of the following: symptoms of straining, difficulty expelling stool, a sense of incomplete evacuation, hard or lumpy stools, prolonged time to stool, or a need for manual maneuvers to pass stool. * Estimated stool consistency \< 4.0 on BSSF (self-reported at screening) within the past month prior to enrollment. * Ability of the participant (in the investigator's opinion) to comprehend the full nature and purpose of the study including possible risks and side effects * Consent to the study and willing to comply with study product and methods
Exclusion criteria
* Major gastrointestinal complication (e.g. Crohn's disease, ulcer) * Prior abdominal surgery that, in the opinion of the investigator, may present a risk for the subject or confound study results * Clinically significant underlying systemic illness that may preclude the subject's ability to complete the trial or that may confound the study outcomes (e.g. bowel cancer, prostate cancer, terminal illness) * Daily consumption of probiotics, prebiotics, fermented milk, and/or yogurt within 2 weeks of screening and throughout the trial other than the provided study products * Non-laxative constipation medication use within 2 weeks of screening, laxative use within 48 hours of screening (rescue medication allowed for intolerable symptoms during study) * Daily use of anticholinergic agents, opioid analgesics, calcium supplements, calcium-channel blockers, and NSAIDs * Anticipated major dietary or exercise changes during the study * Systemic steroid use * Eating disorder * Contraindication to dairy products (e.g., intolerance to lactose or any substance in the study product) * History of alcohol, drug, or medication abuse * Pregnant or lactating female, or pregnancy planned during study period * Participation in another study with any investigational product within 30 days of screening * Investigator believes that the participant may be uncooperative and/or noncompliant and should therefore not participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Whole Gut Transit Time | 4 weeks | The primary endpoint of this clinical trial is whole gut transit time, which will be assessed using abdominal x-rays on days 0 and 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Assessment of Constipation QoL (PAC-QoL) | 4 weeks | The PAC-QoL is a 28-question survey that asks questions on their quality of life. |
| Bowel Function Index | 4 weeks | The Bowel Function Index is a 3-question tool that asks subjects if they have experienced adequate relief of constipation symptoms over the past week. The Bowel Function Index will be completed at days 0 and 28. |
| Adequate Relief of Constipation (Yes/no) | 4 weeks | Adequate relief of constipation (yes/no) This (yes/no) questionnaire will be completed at days 0 and 28. |
| Patient Assessment of Constipation Symptoms (PAC-SYM) | 4 weeks | The PAC-SYM tool asks 12 questions on the symptoms of constipation. Subjects will complete the PAC-SYM at days 0 and 28. |
| Stool Consistency | 4 weeks | Stool consistency will be rated each day in a diary by using the Bristol Stool Scale Form |
| Overall Product Satisfaction | 4 weeks | At the end of the supplementation period, subjects will be asked to rate their overall satisfaction with the study product's ability to relieve their constipation symptoms on a 5-point ordinal scale |
| Adverse Event Frequency | 4 weeks | All adverse events, regardless of relationship with investigational product, will be reported during the 4-week follow-up period. |
| Bowel Movement Frequency | 4 weeks | Subjects will record the number of defecations per day in a diary. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High-dose Probiotic Capsule containing 10 billion cfu B. lactis HN019
B. lactis HN019: Capsule containing 10 billion cfu B. lactis HN019 once a day | 74 |
| Low Dose Probiotic Capsule containing 1 billion cfu B. lactis HN019
B. lactis HN019: Capsule containing 1 billion cfu B. lactis HN019 once a day | 79 |
| Placebo Placebo capsule
Placebo: Capsule containing no probiotic once a day | 71 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 4 | 5 |
| Overall Study | Other | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 10 | 5 |
Baseline characteristics
| Characteristic | Total | High-dose Probiotic | Placebo | Low Dose Probiotic |
|---|---|---|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 12.2 | 41.3 years STANDARD_DEVIATION 12.1 | 41.1 years STANDARD_DEVIATION 12.6 | 42.9 years STANDARD_DEVIATION 12 |
| BMI | 27.0 Kg/m^2 STANDARD_DEVIATION 4.4 | 27.0 Kg/m^2 STANDARD_DEVIATION 4.2 | 26.6 Kg/m^2 STANDARD_DEVIATION 4.7 | 27.4 Kg/m^2 STANDARD_DEVIATION 4.4 |
| Height, M | 1.68 M STANDARD_DEVIATION 0.1 | 1.66 M STANDARD_DEVIATION 0.12 | 1.68 M STANDARD_DEVIATION 0.1 | 1.68 M STANDARD_DEVIATION 0.09 |
| Race/Ethnicity, Customized African-American, Black | 68 participants | 19 participants | 24 participants | 25 participants |
| Race/Ethnicity, Customized Asian | 12 participants | 4 participants | 6 participants | 2 participants |
| Race/Ethnicity, Customized Caucasian, non-Hispanic | 88 participants | 27 participants | 26 participants | 35 participants |
| Race/Ethnicity, Customized Hispanic | 39 participants | 17 participants | 11 participants | 11 participants |
| Race/Ethnicity, Customized Native American | 2 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Other | 15 participants | 6 participants | 4 participants | 5 participants |
| Region of Enrollment United States | 224 participants | 74 participants | 71 participants | 79 participants |
| Sex: Female, Male Female | 161 Participants | 56 Participants | 51 Participants | 54 Participants |
| Sex: Female, Male Male | 63 Participants | 18 Participants | 20 Participants | 25 Participants |
| Weight, Kg | 75.6 Kg STANDARD_DEVIATION 15 | 74.9 Kg STANDARD_DEVIATION 15.2 | 74.3 Kg STANDARD_DEVIATION 14.9 | 77.5 Kg STANDARD_DEVIATION 15.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 74 | 16 / 79 | 20 / 71 |
| serious Total, serious adverse events | 0 / 74 | 0 / 79 | 0 / 71 |
Outcome results
Primary
Whole Gut Transit Time
The primary endpoint of this clinical trial is whole gut transit time, which will be assessed using abdominal x-rays on days 0 and 28
Time frame: 4 weeks
Population: Only 39 out of the 224 enrolled subjects consumed the radio-opaque markers in line with the protocol. Because of the substantial number of protocol deviations and the lack of sufficient evaluable subjects, no further analyses of the study data were performed. The study appears not to have yielded evaluable data.
Secondary
Adequate Relief of Constipation (Yes/no)
Adequate relief of constipation (yes/no) This (yes/no) questionnaire will be completed at days 0 and 28.
Time frame: 4 weeks
Secondary
Adverse Event Frequency
All adverse events, regardless of relationship with investigational product, will be reported during the 4-week follow-up period.
Time frame: 4 weeks
Secondary
Bowel Function Index
The Bowel Function Index is a 3-question tool that asks subjects if they have experienced adequate relief of constipation symptoms over the past week. The Bowel Function Index will be completed at days 0 and 28.
Time frame: 4 weeks
Secondary
Bowel Movement Frequency
Subjects will record the number of defecations per day in a diary.
Time frame: 4 weeks
Secondary
Overall Product Satisfaction
At the end of the supplementation period, subjects will be asked to rate their overall satisfaction with the study product's ability to relieve their constipation symptoms on a 5-point ordinal scale
Time frame: 4 weeks
Secondary
Patient Assessment of Constipation QoL (PAC-QoL)
The PAC-QoL is a 28-question survey that asks questions on their quality of life.
Time frame: 4 weeks
Secondary
Patient Assessment of Constipation Symptoms (PAC-SYM)
The PAC-SYM tool asks 12 questions on the symptoms of constipation. Subjects will complete the PAC-SYM at days 0 and 28.
Time frame: 4 weeks
Secondary
Stool Consistency
Stool consistency will be rated each day in a diary by using the Bristol Stool Scale Form
Time frame: 4 weeks