Yield of Diagnostic Tests and Effects of Crofelemer for Chronic Idiopathic Diarrhea In Non-HIV Patients

• ClinicalTrials.gov Identifier: NCT03898856
• Recruitment Status: Recruiting
• First Posted: April 2, 2019
• Last Update Posted: November 4, 2020
• Sponsor: The University of Texas Health Science Center, Houston
• Collaborator: Napo Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Brooks Cash, The University of Texas Health Science Center, Houston

Study Description

Brief Summary:

The purpose of this study is to evaluate the effectiveness of the drug Crofelemer in the treatment of non-HIV patients with chronic idiopathic diarrhea; to determine the prevalence of identifiable causes of chronic diarrhea in a non-HIV patients; to assess the diagnostic yield, in terms of identification of treatable etiologies, of commercially available diagnostic evaluations in adult, non-HIV patients with chronic idiopathic diarrhea, that is, evaluate which tests, among the standard diagnostic tests commonly conducted as part of the evaluation of chronic idiopathic diarrhea, are most likely to identify a treatable cause of the diarrhea; and to analyze the relationship between chronic idiopathic diarrhea and health-related quality of life and assess the impact of crofelemer treatment on health-related quality of life.

Condition or disease	Intervention/treatment	Phase
Chronic Diarrhea of Unknown Origin	Drug: Crofelemer; Diagnostic Test: Diagnostic tests for cause of chronic diarrhea	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Yield of Diagnostic Tests and Management of Crofelemer for Chronic Idiopathic Diarrhea In Non-HIV Patients: A Pilot Study
• Actual Study Start Date: April 1, 2019
• Estimated Primary Completion Date: April 1, 2022
• Estimated Study Completion Date: April 1, 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: Crofelemer and Diagnostic tests for cause of chronic diarrhea; 125 mg tablets taken by mouth twice daily for 28 days

Drug: Crofelemer; 125 mg tablets taken by mouth twice daily for 28 days; Diagnostic Test: Diagnostic tests for cause of chronic diarrhea; Diagnostic tests include: Esophagogastroduodenoscopy, Colonoscopy, biopsies of the upper gastrointestinal tract (duodenum) and lower gastrointestinal tract (colon), genetic testing for Congenital sucrase-isomaltase deficiency (CSID),Prometheus IBcause Chronic Diarrhea panel, Thyroid Panel, Stool osmolality, Stool Ova and Parasites, Stool Culture, Stool Qualitative Stool Fat, Stool Reducing Substances, Laxative Screening, Lactulose Hydrogen Breath Test, Gastrin Level, Calcitonin Level, Vasoactive Intestinal Polypeptide(VIP) level.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with a 50 percent decrease in mean stool count per week [ Time Frame: Week 4 ]

Secondary Outcome Measures :

1. Number of participants with an improvement in stool consistency by more than 2 levels as measured by the Bristol stool form scale [ Time Frame: week 4 ]
   The Bristol stool form scale is a validated 1-7 scale that correlates to stool form. Type 1 is pebble like stool, type 2 lumpy and hard, type 3 like a sausage with cracks on the surface type 4 like a sausage but smooth and soft, type 5 soft blobs with clear cut edges, type 6 fluffy pieces with ragged edges, mushy stool, type 7watery, no solid pieces Types 5-7 are consistent with diarrhea and for this study a movement to lower types is considered an improvement
2. Change in physical, psychological, and social functioning as measured by the Health-related quality of life (HRQOL) questionnaire [ Time Frame: Baseline,week 4 of treatment ]
   The Medical Outcomes Trust short form questionnaire with 36 questions, most often referred to as SF-36, is a measure of general health status relevant across age, disease and treatment groups, widely used and tested in a range of conditions and settings. The items in SF-36 are divided into eight different domains with overall physical and mental health component summary scores. Domains are physical functioning, role limitations physical, bodily pain, social functioning, general mental health, role limitations emotional, vitality and general health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
3. Number of participants with any abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea [ Time Frame: Baseline ]
4. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Esophagogastroduodenoscopy [ Time Frame: Baseline ]
5. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Colonoscopy [ Time Frame: Baseline ]
6. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Biopsy of duodenum [ Time Frame: Baseline ]
7. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Biopsy of Colon [ Time Frame: Baseline ]
8. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Prometheus IBcause Chronic Diarrhea panel [ Time Frame: Baseline ]
9. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Thyroid Function Tests [ Time Frame: Baseline ]
10. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Stool osmolality [ Time Frame: Baseline ]
11. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Stool Ova and Parasites [ Time Frame: Baseline ]
12. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Stool Culture [ Time Frame: Baseline ]
13. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Stool Qualitative Stool Fat [ Time Frame: Baseline ]
14. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Stool Reducing Substances [ Time Frame: Baseline ]
15. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Laxative Screening [ Time Frame: Baseline ]
16. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Lactulose Hydrogen Breath Test [ Time Frame: Baseline ]
17. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-Gastrin Level [ Time Frame: Baseline ]
18. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-. Calcitonin Level [ Time Frame: Baseline ]
19. Number of participants with abnormal diagnostic test results leading to the identification of the cause of chronic diarrhea-VIP Level [ Time Frame: Baseline ]
20. Change in participant diary descriptors as measured by time of bowel movements per 24 hr period [ Time Frame: Baseline,week 4 of treatment ]
21. Change in participant diary descriptors as measured by number of loose stools per 24 hr period [ Time Frame: Baseline,week 4 of treatment ]
22. Change in participant diary descriptors as measured by consistency of each bowel movement as per the Bristol Stool Form Scale [ Time Frame: Baseline,week 4 of treatment ]
    The Bristol stool form scale is a validated 1-7 scale that correlates to stool form. Type 1 is pebble like stool, type 2 lumpy and hard, type 3 like a sausage with cracks on the surface type 4 like a sausage but smooth and soft, type 5 soft blobs with clear cut edges, type 6 fluffy pieces with ragged edges, mushy stool, type 7watery, no solid pieces Types 5-7 are consistent with diarrhea and for this study a movement to lower types is considered an improvement
23. Change in participant diary descriptors as measured by the presence of urgency with each bowel movement [ Time Frame: Baseline,week 4 of treatment ]
    0-4 visual analog scale (0=none; 4=incontinence)
24. Change in participant diary descriptors as measured by supportive anti-diarrheal medication taken [ Time Frame: Baseline,week 4 of treatment ]
    Yes or no
25. Change in participant diary descriptors as measured by dose of supportive anti-diarrheal medication taken [ Time Frame: Baseline,week 4 of treatment ]
26. Change in participant diary descriptors as measured by number of anti-diarrheal medication taken per 24-hr period [ Time Frame: Baseline,week 4 of treatment ]
27. Change in participant diary descriptor of daily time of administration of crofelemer [ Time Frame: Baseline,week 4 of treatment ]
    Time
28. Change in participant diary descriptor of any new symptoms [ Time Frame: Baseline,week 4 of treatment ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients with chronic diarrhea (defined as 3 non-bloody loose stools per day or more than 20 non-bloody loose stools per week for more ≥ 4 weeks) and Bristol Stool Form Scale for stool consistency of 6/7 with >50% stool without an obvious cause after evaluation for organic etiologies.
• Patients from any ethnicity

Exclusion Criteria:

• Hematochezia (potentially related to an organic cause).
• Subjects less than 18 years of age more than 75 years of age (safety and effectiveness of crofelemer has not been established in these age groups).
• Pregnant females (crofelemer is a Category C drug due to lack of well-controlled studies to study its effects in this population).
• Lactating females (it is unknown if crofelemer is excreted in the human milk and thus may have unknown adverse effects on the nursing infants).
• HIV positive individuals.
• Persons within ability to provide consent and understand the study
• Persons with history of alcohol abuse or binge drinking.
• Persons with history of surgical bowel resection or bariatric surgery in the past 12 months.
• Persons who have undergone cholecystectomy (open or laparoscopic) in the past 3 months.
• Persons receiving antibiotics currently or have received antimicrobials in the past 4 weeks.
• Persons with end-organ failures including end-stage renal disease, end-stage liver disease, or severe heart failure.
• Persons with metastatic hematologic and oncologic malignancies.
• Persons receiving chemo-radiation or immune-modulators for oncologic or rheumatologic conditions.
• Persons with any other known organic gastrointestinal or non-gastrointestinal disease process in which diarrhea is a recognized clinical feature.
• Gluten free diet for previous 3 months and refusal to ingest gluten.

Contacts and Locations

Contacts

Contact: Brooks Cash, MD; 713-500-6677; Brooks.D.Cash@uth.tmc.edu

Contact: Brooks Cash, MD; gi.research@uth.tmc.edu

Locations

United States, Texas

The University of Texas Health Science Center at Houston; Recruiting

Houston, Texas, United States, 77030

Contact: Brooks Cash, MD

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

Napo Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Brooks Cash, MD; The University of Texas Health Sciences Center at Houston

More Information

• Responsible Party: Brooks Cash, Visiting professor, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT03898856
• Other Study ID Numbers: HSC-MS-18-0990
• First Posted: April 2, 2019
• Last Update Posted: November 4, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Brooks Cash, The University of Texas Health Science Center, Houston:

diarrhea; diagnosis; crofelemer; treatment

Additional relevant MeSH terms:

Diarrhea; Signs and Symptoms, Digestive