The present study is a randomized, placebo-controlled, double-blind, parallel-group clinical study designed to assess the effects of IP in individuals with Functional constipation as compared to a placebo. Approximately 205 individuals aged between 18 and 60 years will be screened. Considering a screen failure of 20%, approximately 164 individuals will be randomized in a ratio of 1:1 to receive either the active or placebo. The study will have at least 126 completed participants i.e. 63 partcipants in each study arm after accounting for a dropout/withdrawal rate of 23% at the end of the study. The intervention duration for all the study participants will be 56 days with follow up of upto 84 days. The study flow chart given below indicates the time points at which safety and efficacy assessments will be conducted
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
168
One capsule per day consumed orally before breakfast Duration: 84 days (12 weeks)
One capsule per day consumed orally before breakfast Duration: 84 days (12 weeks)
Anand Multispeciality Hospital
Vadodara, Gujarat, India
AK Superspeciality Clinic
Pune, Maharashtra, India
Gastrohub Hospital
Pune, Maharashtra, India
Lifeline multispecialty Hospital
Pune, Maharashtra, India
Care Multispecialty Hospital
Pune, Maharashtra, India
Krishna Hospital
Varanasi, Uttar Pradesh, India
To assess the effect of VL-BK-02 on changes in the frequency of Complete Spontaneous Bowel Movements (CSBMs)
Severe constipation is defined as no complete spontaneous bowel movements (CSBMs) and an average straining score ≥ 3.0 (CIC; 5-point scale) CSBM has emerged as an attractive symptom-specific primary endpoint for constipation trials, as it integrates the objective, quantitative sign of stool frequency and the subjective, qualitative symptom of sensation of complete defecation
Time frame: per week from baseline to the end of study visit.
To assess the effect of Investigational product (IP) in comparison to baseline and placebo on Stool consistency as assessed by Bristol Stool Form Scale (BSFS) per week from baseline to the end of study visit.
The BSFS is a commonly used ordinal stool-type scale in clinical research and practice that goes from the hardest (type 1) to the softest (type 7). Abnormally hard stools (and in conjunction with other symptoms indicative of constipation) are referred to as types 1 and 2. On the other hand, types 6 and 7 are characterized by unusually loose or watery stools together with other symptoms that point to diarrhea. Stool forms 3-5 are regarded as the most "normal.
Time frame: Baseline to Day 84
To assess the effect of Investigational product (IP) in comparison to baseline and placebo on Constipation symptoms by using Participant Assessment of Constipation Symptoms (PAC-SYM) from baseline to day 14, day 28, day 42, day 56, day 70 and day 84.
Chronic constipation is a common, self-reported, symptom-based disorder, which can significantly impact an individual's health-related quality of life The 12-item questionnaire is divided into three symptom subscales: abdominal (four items); rectal (three items); and stool (five items). Items are scored on 5-point Likert scales, with scores ranging from 0 to 4 (0 = 'symptom absent', 1 = 'mild', 2 = 'moderate', 3 = 'severe', and 4 = 'very severe'). A mean total score in the range of 0-4 is generated by dividing the total score by the number of questions completed; the lower the total score, the lower the symptom burden.
Time frame: Baseline to day 14, day 28, day 42, day 56, day 70 and day 84.
To assess the effect of Investigational product (IP) in comparison to baseline and placebo on Quality of life by using Participant Assessment of Constipation QoL (PAC-QoL)
The PAC-QOL questionnaire is subcategorized into 4 items on physical discomfort, 8 items on psychosocial discomfort, 5 items on treatment satisfaction, and finally 11 items on worries and discomfort. Response choice is a Likert scale from 0 to 4.Higher scores mean higher negative effects on quality of life. Items
Time frame: Baseline to day 14, day 28, day 42, day 56, day 70 and day 84.
To assess the effect of Investigational product (IP) in comparison to baseline and placebo Percentage responders are defined as the number of participants with an increase by 1 or more frequencies of CSBM from baseline to the end of intervention.
Based on EMA guidelines, a CSBM weekly responder will be defined as a participant who experienced more than or equal to 3 CSBMs per week and an increase of ≥ 1 CSBM per week (compared to the baseline).46,47 A "sustained response" will be defined as fulfilling these criteria for the last 4 weeks of treatment.
Time frame: Baseline to Day 84
To assess the effect of Investigational product (IP) in comparison to baseline and placebo in Gut microbiome (alpha and beta diversity) from baseline to end of intervention.
Stool samples will be collected from the participants on Day 0 and Day 56. A window period of ± 3 days will be provided for stool sample collection. Participants will be provided with a stool sample collection kit with sample collection instructions on screening day and day 28. Stool samples will be collected from participants's homes or on site at Day 0 and Day 56. The samples will be further stored for future analysis of metagenome NGS sequencing. Stool samples will be collected from the participants and shipped to the central lab in gel ice pack. Stool samples for NGS will be stored at -80 degrees until shipped to the central lab
Time frame: Baseline to Day 84
To assess the effect of Investigational product (IP) in comparison to baseline and placebo Difference in the usage of rescue medication throughout the study duration as compared to placebo
Bowel movement within 24 hours of consuming the rescue medication will not be considered as an SBM or a CSBM
Time frame: through study completion, an average of Day 84
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