Dose-ranging Efficacy of Polydextrose Supplement on Colonic Transit Time and Symptoms in Adults With Functional Constipation

Study Overview
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Brief Summary
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This study will investigate the effectiveness of Polydextrose, a dietary fiber, at decreasing Colonic Transit Time and the gastrointestinal symptoms of Functional Constipation. One quarter of the subjects will receive 12 g of Polydextrose daily, one quarter will receive 8 g of Polydextrose daily, one quarter will receive 4 g of Polydextrose daily and one quarter will receive a placebo daily.

Official Title
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Dose-ranging Efficacy of Supplementation With Polydextrose, a Dietary Fibre, on Colonic Transit Time and Gastrointestinal Symptoms in Adults With Functional Constipation: A Double-blind, Randomized, Placebo-controlled Trial

Conditions
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Functional Constipation

Intervention / Treatment
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* Dietary Supplement: Litesse powder containing 12 g polydextrose
* Dietary Supplement: Litesse powder containing 8 g polydextrose
* Dietary Supplement: Litesse powder containing 4 g polydextrose
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 70 years. Body mass index between 18.5 and 29.9 kg/m2 (encompasses normal weight and overweight). If female, subject is not of child bearing potential. Defined as females who have had a hysterectomy or oophorectomy, bilateral tubal ligation or are post-menopausal (natural or surgically with > 1 year since last menstruation). OR Female subject of childbearing potential must agree to use a medically approved method of birth control and have a negative urine pregnancy test result. Acceptable methods of birth control include: Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System), Intrauterine devices, Double barrier method, Vasectomy of partner (shown successful as per appropriate follow-up), Tubal ligation, and Non-heterosexual lifestyle (same sex partner). Meets the Rome III criteria for functional constipation as follows: (Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis): Must meet 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 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. Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research. Exclusion Criteria: Major gastrointestinal complication (e.g. Crohn's disease, colitis, celiac disease) 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 participant'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. Laxative use within 48 hours of screening (rescue medication allowed for intolerable symptoms during study). Regular use of any drug or dietary supplement known to cause constipation (e.g. iron, opioids, sucralfate, misoprostol, 5-HT#-antagonists, antacids with magnesium, calcium or aluminum, antidiarrheal medication, anticholinergic agents, calcium supplements, calcium channel blockers, tricyclic antidepressants or NSAIDs), within 1 month before screening. Anticipated major dietary or exercise changes during the study. Systemic steroid use, within 1 month before screening. 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 60 days of screening. Investigator believes that the participant may be uncooperative and/or noncompliant and should therefore not participate in the study. Subject under administrative or legal supervision. Subject who would receive more than 4500 Euros as indemnities for his participation in biomedical research within the 12 last months, including the indemnities for the present study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Litesse powder containing 12 g polydextrose<br>12 g of polydextrose, 1 sachet of powder mixed with water taken daily with breakfast for 2 weeks | Dietary Supplement: Litesse powder containing 12 g polydextrose<br>* 12 g polydextrose<br>* Other names: Litesse powder;|
| Experimental: Litesse powder containing 8 g polydextrose<br>8 g of polydextrose, 1 sachet of powder mixed with water taken daily with breakfast for 2 weeks | Dietary Supplement: Litesse powder containing 8 g polydextrose<br>* 8 g polydextrose, 4 g maltodextrin<br>* Other names: Litesse powder;|
| Experimental: Litesse powder containing 4 g polydextrose<br>4 g of polydextrose, 1 sachet of powder mixed with water taken daily with breakfast for 2 weeks | Dietary Supplement: Litesse powder containing 4 g polydextrose<br>* 4 g polydextrose, 8 g maltodextrin<br>* Other names: Litesse powder;|
| Placebo Comparator: Placebo<br>Maltodextrin, 1 sachet of powder mixed with water taken daily with breakfast for 2 weeks | Dietary Supplement: Placebo<br>* 12 g Maltodextrin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Colonic Transit Time From Baseline to Day 15 | Assessed using abdominal x-ray. Subjects will take 24 radiopaque markers for 6 consecutive days (144 radiopaque markers in total) immediately preceding the x-ray dates. | Baseline and Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Participant Assessment of Constipation Symptoms (PAC-SYM) From Baseline to Day 15 | Assessed using the PAC-SYM questionnaire (overall score, abdominal symptoms score, rectal symptoms score, and stool symptoms score). The PAC-SYM was developed as a brief, easily administered tool to assess symptom frequency and severity of chronic constipation. The authors used a definition for constipation was based on the Rome II criteria. This 12-item self-report measure is divided into the 3 symptom subscales of: abdominal, rectal and stool subscales. All items (sub-scores and the total score) are scored on a five-point Likert scale ranging from 0 (absence of symptom) to 4 (very severe) where lower scores are better. Scores for the total number of non-missing items within the subscale or total score are summed and divided by the total number of non-missing items for that subscale or total score. | Baseline and Day 15 | 
| Change in Participant Assessment of Constipation Quality of Life (PAC-QoL) From Baseline to Day 15 | Assessed using the PAC-QoL questionnaire (Overall Score, Worries and Concerns Score, Physical Discomfort Score, Psychosocial Discomfort Score, and Satisfaction Score) The Patient Assessment of Constipation (PAC) was developed to address the need for a disease-specific patient-reported outcomes measure. It includes components from complementary symptom and quality of life questionnaires. The PAC-QOL contains 28 items grouped into 4 subscales covering: worries and concerns (11 items), physical discomfort (4 items), psychosocial discomfort (8 items), and satisfaction (5 items). A 5-point Likert response scale, ranging from 0 (not at all / none of the time) to 4 (extremely / all of the time), where lower scores are better. Scores are computed as the average non-missing item response within the subscale where each score is given equal weight; the global score is calculated as the mean of the 28-items. | Baseline and Day 15 | 
| Change in Bowel Function Index From Baseline to Day 15 | Assessed using the Bowel Function Index questionnaire (total score, ease of defecation, feeling of incomplete bowel evacuation, and personal judgement of constipation). Each of the three questions used a numerical analog scale (0 = easy/no difficulty/not at all, 100 = very strong/very difficult) for grading purposes. The three questions were calculated as single scores as well as by a total score defined as the average of the three questions. | Baseline and Day 15 | 
| Change in Adequate Relief of Constipation Symptoms From Baseline to Day 15 | Assessed using single question dichotomous tool. Adequate relief quantified the difference in the number of participants experiencing relief from constipation between participants supplemented with Litesse and those supplemented with a placebo at baseline and day 14. The units of analysis for the relief questionnaire were the number of participants who reported relief from constipation. | Baseline and Day 15 | 
| Change in Stool Frequency From Baseline to Day 15 | Participants will record the number of defecations per day in a daily diary | 14 day run-in and Week 2 of the 14-day supplementation period | 
| Change in Stool Consistency From Baseline to Day 15 | Stool consistency will be rated each day in a diary by using the Bristol Stool Scale Form. Bristol Stool Scale: The BSS is a categorical scale ranging from 1 to 7 that interprets the consistency of a single bowel movement; a single score is recorded and used for analysis. Lower scores are associated with hard and lumpy consistencies while higher scores are associated with soft or liquid consistencies. Generally, an optimal BSS scores ranges from 3 to 5. | 14 day run-in and Week 2 of the 14-day supplementation period | 
| Change in the Degree of Straining During Defecation From Baseline to Day 15 | Degree of straining for each bowel movement will be recorded in a daily diary using a 5-point scale. The degree of straining is a rating scale ranging from 1 (not at al) to 5 (an extreme amount) that interprets the degree to which an individual must strain during a unique defecation; a single core is recorded and used for analysis. Scores were calculated as the weekly average of the daily degree of straining (1-5) where a lower score represented less straining. | 14 day run-in and Week 2 of the 14-day supplementation period | 
| Change in the Sensation of Complete Bowel Emptying From Baseline to Day 15 | Sensation of complete bowel emptying for each bowel movement will be recorded in a daily diary on a dichotomous yes or no scale. The change in the sensation was defined as the change from baseline to week 2 in the percentage of complete bowel movements (CBMs) between participants supplemented with Litesse and those supplemented with a placebo. It assessed whether the participant felt as though their bowel movement was complete. The units of analysis for the sensation of complete bowel emptying was the weekly percentage of complete bowel movements, for each participant at run-in (week -1), week 1 and week 2. | 14 day run-in and Week 2 of the 14-day supplementation period | 
| Change in the Severity of Abdominal Discomfort From Baseline to Day 15 | Severity of abdominal discomfort will be recorded each day in a daily diary on a 5-point scale. The severity of abdominal discomfort was calculated from a rating scale ranging from 1 (not at all) to 5 very severe); a single score was recorded and used for analysis. Scores were calculated as the weekly average of the daily degree of discomfort where a lower score represented less straining. | 14 day run-in and Week 2 of the 14-day supplementation period | 
| Change in the Bloating Severity From Baseline to Day 15 | Severity of bloating will be recorded each day in a daily diary on a 5-point scale. The severity of abdominal bloating was calculated from a rating scale ranging from 1 (not at all) to 5 very severe); a single score was recorded and used for analysis. Scores were calculated as the weekly average of the daily degree of bloating where a lower score represented less straining. | 14 day run-in and Week 2 of the 14-day supplementation period | 
| Overall Product Satisfaction | Participants 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. The overall product satisfaction questionnaire consists of a single question that provides insight regarding the participants satisfaction on the product's ability to relieve constipation symptoms. The score that the participant indicates is considered the total score and no sub-scores are calculated. It is a rating scale that ranges from 1 (not at all satisfied) to 5 (very satisfied) where a higher score at the end-of-study indicates an improvement. | Assessed at Day 15 (end of study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Constipation, Polydextrose, Dietary Fiber, PAC-QoL, Colonic Transit Time, PAC-SYM