The Effect of CSP01 on Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation

• ClinicalTrials.gov Identifier: NCT03054506
• Recruitment Status: Completed
• First Posted: February 15, 2017
• Results First Posted: August 20, 2019
• Last Update Posted: August 20, 2019
• Sponsor: Massachusetts General Hospital
• Collaborator: Gelesis, Inc.
• Information provided by (Responsible Party): Kyle Staller, MD, MPH, Massachusetts General Hospital

Study Description

Brief Summary:

Constipation is a common gastrointestinal motility disorder that is often chronic, negatively affects patients' daily lives. Constipation occurs when bowel movements become difficult or less frequent.This study is being done to study the effectiveness of the hydrogel capsule, CSP01, compared to the active control (carboxymethylcellulose) and placebo (non-medicine sugar pill), to relieve constipation among subjects with chronic idiopathic constipation (CIC) or with irritable bowel syndrome with constipation (IBS-C).

Condition or disease	Intervention/treatment	Phase
Constipation; Chronic Idiopathic Constipation; Irritable Bowel Syndrome With Constipation	Device: CSP01; Device: Carboxymethylcellulose (CMC); Device: Placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Single Center, Double-blind, Parallel-group, Placebo-controlled Study Assessing the Effect of CSP01 on Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation
• Actual Study Start Date: March 7, 2017
• Actual Primary Completion Date: May 10, 2018
• Actual Study Completion Date: February 1, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: CSP01; Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief.	Device: CSP01; Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Active Comparator: Carboxymethylcellulose (CMC); Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day.	Device: Carboxymethylcellulose (CMC); Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Placebo Comparator: Placebo; Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day.	Device: Placebo; Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Colonic Transit Time (CTT) [ Time Frame: Up to 1 week; measured once during the run-in-period and again during third week of the treatment period ]
   Colonic Transit Time is the amount of time (in minutes) that the SmartPill capsule spent in the large intestine before expulsion. We measured the difference between CTT pre-treatment and post-treatment and calculated the mean difference for each treatment group. Negative values equal a reduction in CTT.

Secondary Outcome Measures :

1. Complete Spontaneous Bowel Movement (CSBM) Frequency Rate [ Time Frame: 55 days (baseline, treatment, & follow-up) ]
   Average number of Complete Spontaneous Bowel Movements per day (BMs where participant felt that they emptied their bowels). More CSBMs are interpreted as a better outcome.
2. Stool Consistency [ Time Frame: 55 days (baseline, treatment, & follow-up) ]

   Stool consistency for each bowel movement based on the Bristol Stool Scale A descriptive numerical scale from 1 to 7 where lower numbers indicate constipation, numbers toward the middle indicate normal stool consistence, and the highest numbers indicate diarrhea. Therefore middle scores mean a better outcome

   1= hard lumps 2 = lumpy sausage 3 = cracked sausage 4 = smooth sausage 5 = soft lumps 6 = mushy 7 = watery

3. Ease of Passage Rating [ Time Frame: 55 days (baseline, treatment, & follow-up) ]

   Patient assessment of the ease with which bowel movements are passed using a descriptive numerical scale where lower numbers indicate difficult passage of stool, numbers toward the middle indicate more normal passage of stool, and numbers on the highest end indicate abnormally urgent passage of stool. Middle scores indicate a better outcome.

   1. = manual disimpaction needed
   2. = enema needed
   3. = straining needed
   4. = normal
   5. = urgent without pain
   6. = urgent with pain
   7. = incontinent
4. Patient's Assessment of Abdominal Discomfort [ Time Frame: 55 days (baseline, treatment, & follow-up) ]
   Patient's daily assessment of abdominal discomfort using a numerical rating scale of 0 to 10, where 0 = no discomfort at all and 10 = severe discomfort. Higher scores mean a worse outcome.
5. Patient Assessment of Bloating Severity [ Time Frame: 55 days (baseline, treatment, & follow-up) ]
   Patient's daily assessment of bloating severity using a numerical rating scale from 0 to 10 where 0 = no bloating at all and 10 = severe bloating. Higher scores mean a worse outcome.
6. Patient Assessment of Constipation Severity [ Time Frame: 55 days (baseline, treatment, & follow-up) ]
   Patient's daily assessment of constipation severity using a numerical rating scale from 0 to 10 where 0 = no constipation at all and 10 = severe constipation. Higher numbers mean a worse outcome.
7. Relief Rating [ Time Frame: 55 days (baseline, treatment, & follow-up) ]
   Patient's feeling of overall relief after each bowel movement using a numerical rating scale from 0 to 10 where 0 = no relief and 10 = complete relief. Higher scores mean a better outcome (feeling more relief after a bowel movement).
8. Patient Assessment of Constipation - Symptoms (PAC-SYM) [ Time Frame: Day -14 to Day 22 ]

   Patient assessment of constipation symptom severity questionnaire. A validated 12-question questionnaire.

   Numerical scale from 0 to 4 where 0 = absent and 4 = very severe. Possible total score ranges from 0 to 48. Higher total PAC-SYM scores mean a worse outcome.

   PAC-SYM was completed at four time-points (Day -14, Day 0, Day 15, & Day 22). Scores were aggregated based on time period as either pre- (Day -14 & Day 0) or post- (Day 15 & Day 22) treatment start. Values reported are averages based on patient total scores from these time points. Data was specifically analyzed based on patient diagnosis in addition to treatment.

9. Patient Assessment of Constipation - Quality of Life (PAC-QOL) [ Time Frame: Day -14 to Day 22 ]

   Patient Assessment of Constipation Quality of Life Questionnaire. A validated questionnaire containing 28 total questions with four sub-sections each broadly ranging from "not at all" to "all of the time" on 0 to 4 scales.

   Possible total range is 0 to 112. An overall higher total score on the PAC-QOL means a worse outcome. PAC-QOL was completed at four time-points (Day -14, Day 0, Day 15, & Day 22). Scores were aggregated based on time period as either pre- (Day -14 & Day 0) or post- (Day 15 & Day 22) treatment start. Values reported are averages based on patient total scores from these time points. Data was specifically analyzed based on patient diagnosis in addition to treatment.

10. Need for Rescue Laxatives [ Time Frame: 55 days (baseline, treatment, & follow-up) ]

    Number of total days that rescue laxatives were used by participants in each treatment group.

    (The number of days that rescue laxatives were used by each individual patient was calculated and added to the treatment group total)

11. Spontaneous Bowel Movement (SBM) Frequency [ Time Frame: 55 days (baseline, treatment, & follow-up) ]
    Average number of Spontaneous Bowel Movements per day. (Spontaneous Bowel Movements include both complete and incomplete bowel movements)

Eligibility Criteria

• Ages Eligible for Study: 22 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age 22-70 years old
2. BMI >18.5 and <35 kg/m2
3. Rome III criteria for functional constipation or IBS-C
4. Continued IBS-C or CIC throughout Run-in period
5. Compliant with reporting during Run-in (confirm the presence of constipation during the 7-day Run-in baseline period; patients are required to report an average of <3 continuous spontaneous bowel movements [CSBMs] and ≤6 spontaneous bowel movements [SBMs] per week via the interactive web response system).
6. Ability to follow verbal and written instructions
7. Ability to record daily bowel habits, including frequency, stool consistency (BSFS), straining (EoPS), completeness of evacuation, and Patient Reported Outcomes (PROs) (abdominal discomfort, severity of constipation, bloating, overall relief)
8. Informed consent form signed by the subjects

Exclusion Criteria:

1. History of loose stools
2. History of irritable bowel syndrome with diarrhea (IBS-D) or mixed irritable bowel syndrome (IBS-M)
3. Non-compliance with reporting during Run-in
4. Patients reporting laxative, enema, and/or suppository usage for >2 days or any usage of a prohibited medication during the Run-in period
5. Patients reporting watery stools for any SBM (Type 7 on the Bristol Stool Form Scale [BSFS]) or loose (mushy) stools for >1 SBM (Type 6 on the BSFS) in the absence of laxatives during Run-in
6. GI motility obstruction or GI tract structural abnormality
7. Current use of prescribed or illicit opioids
8. History of pelvic floor dysfunction
9. Need for manual maneuvers in order to achieve a BM
10. History of GI lumen surgery at any time or other GI or abdominal operations within 60 days prior to entry into the study
11. History of high-dose stimulative or cathartic laxative abuse as judged by investigator team
12. Neurological disorders, metabolic disorders, or other significant disease that would impair their ability to participate in the study
13. Cardiovascular disease, diabetes, cancer, Crohn's disease, ulcerative colitis
14. BMI of <18.5 or >35 kg/m2
15. Pregnancy (or positive serum or urine pregnancy test(s) in females of childbearing potential) or lactation
16. Absence of contraception in females of childbearing potential
17. History of allergic reaction to carboxymethylcellulose, citric acid, sodium stearyl fumarate, raw cane sugar, gelatin, or titanium dioxide
18. Administration of investigational products within 1 month prior to Screening Visit
19. Exclusion of colonic inertia with symptoms of < 1 BM per 2 weeks
20. Subjects anticipating surgical intervention during the study
21. Known history of diabetes (type 1 or 2)
22. History of eating disorders including binge eating (except mild binge eater)
23. Supine SBP > 160 mm Hg and/or supine DBP > 95 mm Hg (mean of two consecutive readings)
24. Angina, coronary bypass, or myocardial infarction within 6 months prior to Screening Visit
25. History of swallowing disorders
26. Esophageal anatomic abnormalities (e.g., webs, diverticuli, rings)
27. History of gastric bypass or any other gastric surgery
28. History of small bowel resection (except if related to appendectomy)
29. History of gastric or duodenal ulcer
30. History of gastroparesis
31. History of abdominal radiation treatment
32. History of pancreatitis
33. History of intestinal stricture (e.g., Crohn's disease)
34. History of intestinal obstruction or subjects at high risk of intestinal obstruction including suspected small bowel adhesions
35. History of malabsorption
36. History of sucrose intolerance
37. History of hepatitis B or C
38. History of human immunodeficiency virus
39. History of cancer within the past 5 years (except adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer)
40. Any other clinically significant disease interfering with the assessments of Gelesis100, according to the Investigator (e.g., disease requiring corrective treatment, potentially leading to study discontinuation)
41. HbA1c > 8.5% (> 69 mmol/mol)
42. Positive test for drugs in the urine
43. Any relevant biochemical abnormality interfering with the assessments of Gelesis100, according to the Investigator
44. Antidiabetic medications within 1 month prior to Screening Visit (except stable dose of metformin, ≤ 1500 mg/day, for at least 1 month in subjects with type 2 diabetes)
45. Medications requiring mandatory administration with meal at lunch or dinner
46. Anticipated requirement for use of prohibited concomitant medications
47. Implanted or externally worn medical device such as, but not limited to, a pacemaker, infusion pump, or insulin pump

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Gelesis, Inc.

Investigators

• Principal Investigator: Kyle Staller, MD, MPH; Massachusetts General Hospital

  Study Documents (Full-Text)

Documents provided by Kyle Staller, MD, MPH, Massachusetts General Hospital:

Study Protocol and Statistical Analysis Plan  [PDF] October 30, 2017

Informed Consent Form  [PDF] October 25, 2017

More Information

• Responsible Party: Kyle Staller, MD, MPH, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03054506
• Other Study ID Numbers: 2016P001751
• First Posted: February 15, 2017
• Results First Posted: August 20, 2019
• Last Update Posted: August 20, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Irritable Bowel Syndrome; Syndrome; Constipation; Disease; Pathologic Processes; Signs and Symptoms, Digestive; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Carboxymethylcellulose Sodium; Laxatives; Gastrointestinal Agents