臨床研究等提出・公開システム

A Single-Center, Prospective, Open(masking not use), Single Arm
Study. Examination of the effectiveness of probiotics for elderly patients with chronic constipation.

Examination of the probiotics for chronic constipation symptoms
(PCC Trial)

50

The 49 FAS cases were included in the analysis. The mean age was 77.0 years, standard deviation 6.8 years, median 77.0 years, minimum 66 years, and maximum 89 years. Gender was male 24 (49.0%) and female 25 (51.0%); 4 (8.2%) were positive for H. Pylori infection and 20 (40.8%) had a history of H. Pylori infection. 26 (53.1%) were still taking PPIs. Seven patients (14.3%) were still taking Bayaspirin. Forty patients (81.6%) had no history of taking gastroprokinetic agents, and 9 (18.4%) were taking them continuously. Three patients (6.1%) had a history of taking laxatives, and 19 (38.8%) were continuing to do so. The mean, standard deviation, median, minimum, and maximum values of the Bristol Stool Scale were 3.0, 1.3, 3.0, 0, and 5, respectively. The duration of constipation illness was 0 years in 9 patients (18.4%), 1-5 years in 18 patients (36.7%), 6-10 years in 7 patients (14.3%), 11-20 years in 5 patients (10.2%), 21 years or more in 8 patients (16.3%) and unknown in 2 patients (4.1%).

Of the 50 enrolled patients, one patient who never received study treatment was excluded from the FAS and SAS, resulting in 49 cases for analysis; there were no PPS exclusions, so the PPS was consistent with the FAS. Two patients (one due to an adverse event and one due to loss of follow-up of the study subject) discontinued study drug before the 4-week treatment period (28 days of treatment: VISIT (3)), and two patients (one due to an adverse event and one due to the investigator's judgment that the study could not be continued) at the 8-week treatment period (56 days of treatment: VISIT (4)). Forty-five patients remained on study drug until the end of the 8-week treatment period (Treatment Week 56: VISIT (4)).

Three (3) cases and three (3) adverse events occurred. One (1) case of abdominal pain, one (1) case of heartburn/stomachburn/stomachache, and one (1) case of drowning. Serious adverse events included one (1) case of drowning, but a causal relationship to the study drug was ruled out. Adverse events with undeniable causal relationship to the study drug included one case of abdominal pain (yes) and one case of heartburn/stomachburn/stomachache (undeniable). Adverse events that led to discontinuation of the study occurred in all three cases.

For the 49 patients included in the analysis (FAS), there was significant improvement in the primary endpoint of change in defecation score on the Bristol Stool Scale between pre-treatment and 8 weeks (56 days) of treatment. There was no significant improvement in the severity of belching score (7-day average). On the JPAC-QOL, there were significant improvements in "overall score," "physical discomfort," and "worry/concern" at 4 weeks (28 days) and 8 weeks (56 days) of treatment, and in "mental discomfort" at 8 weeks (56 days) of treatment. On the modifiedCSS (mCSS), significant improvement was noted in "Total Score" at 4 weeks (28 days) and 8 weeks (56 days) of treatment, and in "Painful Effort to Defecate" at 4 weeks (28 days) of treatment. On the Izumo Scale, significant improvements were seen in "total score," "heartburn," and "constipation" at 4 weeks (28 days) and 8 weeks (56 days) of treatment, and in "stomach pain," "upset stomach," and "diarrhea" at 4 weeks (28 days) of treatment. In the Dietary Variety Score (DVS), food diversity improved significantly at 4 weeks (28 days) and 8 weeks (56 days) of treatment. These results suggest that 8 weeks (56 days) of continuous intake of the probiotic used in this study (Biothree OD tablets) promotes softening of stool properties and improves chronic constipation in the elderly. In addition, 8 weeks (56 days) of continuous probiotic intake improved JPAC-QOL, modifiedCSS (mCSS), and upper gastrointestinal symptoms such as heartburn, stomach pain, and upset stomach, and improved food diversity.

Data were obtained from 49 patients (mean +- standard deviation 77.0 +- 6.8), 24 males (49.0%) and 25 females (51.0%), who were included in the analysis (FAS). Probiotics (Biothree OD tablets) improved stool characteristics after 8 weeks of treatment (56 days of administration). After 4 weeks of treatment (28 days of administration), the improvement was mild, and it would take 8 weeks (56 days) to obtain constipation improvement from improvement of the intestinal microbiota.

July. 18, 2023

No

not applicable

https://jrct.mhlw.go.jp/latest-detail/jRCTs031210344

Asaoka Daisuke

Juntendo Tokyo Koto Geriatric Medical Center

3-3-20, Shinsuna, Koto-ku, Tokyo 136-0075

daisuke@juntendo.ac.jp

Asaoka Daisuke

Juntendo Tokyo Koto Geriatric Medical Center

3-3-20, Shinsuna, Koto-ku, Tokyo 136-0075

+81-3-5632-3111

daisuke@juntendo.ac.jp

Complete

Sept. 24, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1.Males and females between 65 and 90 years of age at the time of consent.
2.Patients who have been diagnosed with chronic constipation by ROME IV.
3.Patients who have given their written consent to participate in this study.

1.Patients corresponding to 6 (muddy stool) and 7 (watery stool) on the Bristol Stool Form Scale.
2.Patients who have or are suspected of having abnormal recto-anal function.
3.Patients who have been diagnosed with organic abnormalities that cause constipation by colonoscopy within 5 years.
4.Patients with a history of surgical resection of the stomach, gall bladder, small intestine, or large intestine (except for appendicitis and benign polypectomy).
5.Patients with a history of or currently suffering from celiac disease, inflammatory bowel disease (Crohn's disease or ulcerative colitis), or ischemic colitis.
6.Patients who currently have infectious enteritis.
7.Patients with obvious mechanical obstruction (intestinal obstruction due to hernia, etc.), giant colon, or giant rectum.
8.Patients who have had or are currently suffering from malignant tumors of the digestive system (except for gastrointestinal cancers that have been cured by endoscopic treatment).
9.Patients who are currently suffering from serious cardiovascular, respiratory, renal, hepatic, digestive (except for chronic constipation), hematological, neurological, or psychiatric diseases (including insomnia with constant use of sleeping pills, but not including patients who take sleeping pills only for insomnia).
10.Patients who have had or are currently suffering from Parkinson's disease.
11.Patients who are currently suffering from hyperthyroidism or hypothyroidism.
12.Patients who have participated or are currently participating in clinical trials, post-marketing clinical trials, or clinical research for other ethical drugs or medical devices within three month prior to obtaining consent.
13.Patients who are abusing alcohol and drugs.
14.Patients with a history of allergy caused by the study drug (study drug: lactobacillus, saccharobacillus, butyric acid bacteria, additives).
15.Patients who regularly use probiotics other than the protocol treatment (However, even if they have been discontinued more than 2 weeks prior to enrollment.)
16.Patients who regularly use medicines that affect bowel movements (antibiotics, diarrheals) or health foods/supplements (lactic acid bacteria, bifidobacteria, oligosaccharides, dietary fiber, etc. However, foods such as yogurt are acceptable.).
17.Other patients who are judged by the principal investigator or sub-investigator to be inappropriate to participate in this study.

Both

Chronic constipation

Administration of study drug

Chronic constipation,Gut microbiota

Intake of the probiotics

Amount of change in defecation score* on the Bristol Stool Form Scale between pre-treatment and treatment week 8 (day 56).
*The stool properties score (1-7) on the Bristol Scale is used as the score, and the score is set to "0" on days when there is no defecation. Defined as the total of the values obtained by subtracting 4, which is considered to be a normal stool on the Bristol Scale, for 7 consecutive days.
If there is a missing measurement in seven consecutive days, the average value of the data excluding the missing days is adopted.

1. Amount and rate of change in the number of bowel movements (7-day average) between pre-treatment and treatment week 4 (day 28), and between pre-treatment and treatment week 8 (day 56).
If there is a missing measurement in seven consecutive days, the average value of the data excluding the missing days is adopted.
2. Amount of change in the defecation score of the Bristol Stool Form Scale between pre-treatment and treatment week 4 (day 28).
3. Amount and rate of change in JPAC-QOL total score and each subscale score between pre-treatment and treatment week 4 (day 28), and between pre-treatment and treatment week 8 (day 56).
4. Amount and rate of change in ModifiedCSS (mCSS) total score and each endpoint between pre-treatment and treatment week 4 (day 28), and between pre-treatment and treatment week 8 (day 56).
5. Amount and rate of change in each questionnaire score between pre-treatment and treatment week 4 (day 28), and between pre-treatment and treatment week 8 (day 56).
Izumo scale, and DVS (food diversity questionnaire)
6. Amount and rate of change in the severity of strain score (7-day average) between pre-treatment and treatment week 4 (day 28), and between pre-treatment and treatment week 8 (day 56).
*: The difference in the severity of strain is in 5 levels (1: no strain, 2: slight strain, 3: some strain, 4: strong strain, 5: very strong strain)
If there is a missing measurement in seven consecutive days, the average value of the data excluding the missing days is adopted.
7. Amount and rate of change in TG/HDL-C ratio between pre-treatment and treatment week 4 (day 28), and between pre-treatment and treatment week 8 (day 56).
8. Amount and rate of change in nutritional status assessment between pre-treatment and treatment week 4 (day 28), and between pre-treatment and treatment week 8 (day 56).
9.Variation and rate of change in intestinal microflora between pre-treatment and treatment week 4 (day 28), and between pre-treatment and treatment week 8 (day 56)
Comparison of intestinal microbiota (Butyrate-producing bacteria occupancy and others), diversity analysis, principal coordinate analysis, LEfSe analysis

+81-3-5802-1584

Aug. 03, 2021

none