Teduglutide for Enterocutaneous Fistula (ECF)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Teduglutide is safe and feasible to be given for the treatment of enterocutaneous fistula (ECF). The hypothesis is that the drug will be well tolerated and will improve the volume of daily ECF output as well as improve the functional quality of life.

Official Title
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Teduglutide for Treatment of Enterocutaneous Fistula (ECF) - a Pilot Study to Demonstrate Safety and Feasibility

Conditions
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Postoperative Fistula

Intervention / Treatment
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* Drug: Teduglutide
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 Enterocutaneous fistula (ECF) that could be secondary to volvulus, injury, prior trauma or surgery, or vascular ischemia Exclusion Criteria: Perianal fistula Clinical suspicion of inflammatory bowel disease History of radiation enteritis or sprue (as defined by history) Active (<1 year) alcohol or drug abuse Significant hepatic, or cardiac diseases as defined as: Hepatic: aspartate aminotransferase (AST) > 2 times upper limit of normal (10-40 U/L) Cardiac: unstable angina or evidence of active myocardial ischemia (elevated troponin level drawn by clinical suspicion) Severe renal dysfunction: serum creatinine > 2 times upper limit of normal (0.6-1.5 mg/dL) Received glutamine less than 4 weeks prior to screening Receiving growth factors (erythropoietin, granulocyte colony-stimulating factor, granulo-cyte-macrophage colony stimulating factor, and human growth hormone) Pregnancy or lactation (women of childbearing age will be excluded if they do not agree to either complete sexual abstinence during the study or if they refuse to use at least two forms of highly effective contraception such as oral contraception, injectable or implantable contraception, vaginal rings, or intrauterine devices (IUD)) Active malignancy or suspicion for gastrointestinal malignancy on CT scan Not capable of understanding or not willing to adhere to the study visit schedule and drug administration requirements Family history of intestinal malignancy (gastric, small intestine, colon) Personal or family history of hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, first degree relative with colon cancer Positive hemoccult (per rectum) Abnormal baseline electrocardiogram (ECF) suggestive of congestive heart failure or underlying cardiac disease Taking oral benzodiazepines, barbiturates, or phenothiazines

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard of Care followed by Teduglutide<br>Participants in this group will receive standard of care treatment for the first 8 weeks followed by daily Teduglutide for the next 8 weeks. Subjects with a favorable response will be offered an open label extension during which they will continue to receive teduglutide for up to another 12 months or permanent fistula closure. | Drug: Teduglutide<br>* Daily 0.05 mg/kg Teduglutide administered subcutaneously.<br>* Other names: Gattex;Other: Standard of Care<br>* The standard of care treatment of ECF which includes meticulous wound care, optimizations of nutrition, use of acid-suppression medications and anti-motility agents as per treating physician discretion.<br>|
| Experimental: Teduglutide followed by Standard of Care<br>Participants in this group will receive daily Teduglutide treatment for the first 8 weeks followed by standard of care for the next 8 weeks. Subjects with a favorable response will be offered an open label extension during which they will continue to receive teduglutide for up to another 12 months or permanent fistula closure | Drug: Teduglutide<br>* Daily 0.05 mg/kg Teduglutide administered subcutaneously.<br>* Other names: Gattex;Other: Standard of Care<br>* The standard of care treatment of ECF which includes meticulous wound care, optimizations of nutrition, use of acid-suppression medications and anti-motility agents as per treating physician discretion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Average 3-day Fistula Percent Volume | Percent fistula volume will be reported from the participant | Baseline, Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Ceased Fistula Output | As evaluated by treating physician of having at least 1 ceased fistula output | Up to 16 weeks | 
| Quality of Life as Measured by ASCQ-Me® v2.0 Social Functioning - Short Form | Adult Sickle Cell Quality of Life Measurement (ASCQ-Me) Version 2.0 Social Functioning - Short Form questionnaire has a total score ranging from 5-25 with the higher score indicating a healthier status. | Up to 16 weeks | 
| Quality of Life as Measured by the ASCQ-Me® v2.0 Sleep Impact - Short Form | Adult Sickle Cell Quality of Life Measurement (ASCQ-Me) Version 2.0 Sleep Impact - Short Form questionnaire has a total score ranging from 5-25 with the higher score indicating a healthier status | Up to 16 weeks | 
| Quality of Life as Measured by the PROMIS Scale v1.2 - Global Health | Patient Reported Outcome Measures Information Systems Global Health has a total score ranging from 10-50 with the higher score indicating a healthier status | Up to 16 weeks | 
| Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Belly Pain 5a | Patient Reported Outcome Measures Information Systems (PROMIS-GI) Gastrointestinal Belly Pain 5a questionnaire has a total score ranging from 1-25 with the lower score indicating a healthier status | Up to 16 weeks | 
| Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Diarrhea 6a | Patient Reported Outcome Measures Information Systems (PROMIS-GI) Gastrointestinal Diarrhea 6a questionnaire has a total score ranging from 1-30 with the lower score indicating a healthier status | Up to 16 weeks | 
| Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Nausea and Vomiting 4a | Patient Reported Outcome Measures Information Systems (PROMIS-GI) Gastrointestinal Nausea and Vomiting 4a questionnaire has a total score ranging from 1-20 with the lower score indicating a healthier status | Up to 16 weeks | 
| Quality of Life as Measured by the PROMIS Scale v2.0 - Ability to Participate in Social Roles and Activities - Short Form 8a | Patient Reported Outcome Measures Information Systems (PROMIS) Ability to Participate in Social Roles and Activities - Short Form 8a questionnaire has a total score ranging from 8-40 with the lower score indicating a healthier status | Up to 16 weeks |