Autologous Muscle Fiber Fragment Injections

Study Overview
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Brief Summary
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To regenerate functional anal sphincter muscle using muscle fiber fragments that contain muscle precursor cells (MPCs)

Detailed Description
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The Study hypothesizes that efficient re-assembly of injected fragments within host muscle tissue along the fiber direction of native muscle will be induced. It is anticipated that these fiber fragments would integrate into the host vascular and neural network.

Official Title
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Autologous Muscle Fiber Fragment Injections for the Treatment of Fecal Incontinence

Conditions
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Fecal Incontinence

Intervention / Treatment
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* Procedure: Muscle Fiber Fragment (MFF) Injections


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age participants must experience 4 or more Fecal Incontinence (FI) episodes per 2 week period participants must score >10 on Cleveland Clinic Fecal Incontinence Severity Scoring System (CCIS) participants must have had symptoms for at least 12 months participants who have failed standard medical and surgical treatments for FI participant will undergo anorectal manometry (ARM) testing participants will undergo endoscopic anal ultrasound and demonstrate an anatomic defect of the anal sphincter complex of at least 30 degrees women of childbearing potential must use acceptable contraceptives during this study Exclusion Criteria: participants with symptomatic anorectal disease including symptomatic hemorrhoid disease, anal fissure or fistula causing symptoms such as bleeding, swelling, pain, or drainage participants with pre-existing ano-rectal pain of any cause participants with incontinence of flatus only chronic watery diarrhea which is the primary cause for fecal incontinence acute or chronic anorectal infections (including proctitis, recurrent abscesses, fistulae) presence of anorectal tumors active proctitis or inflammatory bowel disease previous injection of internal anal sphincter (IAS) with bulking agents participants requiring immunosuppression or who have any malignant disease within 3 years of enrollment participants with a defined bleeding disorder diagnosed and treated by a hematologist other exclusions include history of pelvic radiation, rectal prolapse, anorectal malformations, anorectal surgery within the previous 12 months, or treatments using injection or infrared coagulation for treatment of hemorrhoids participants with neurologic disease characterized by significant peripheral neuropathy or spinal cord dysfunction women who are pregnant, breastfeeding, or have had a child within the last year participants with a history of unstable cardiac function (New York Heart Association Functional Classification III or IV) or unstable pulmonary function requiring home oxygen, or abnormal kidney function (Cr >1.5 mg/dl or on dialysis) or uncontrolled diabetes (Hemoglobin A1C > 8 mg/dl) participants with anemia (hemoglobin <10g, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2 times normal) or increased bilirubin >1.5mg/dl participants with Hepatitis B or C, or human immunodeficiency virus (HIV)-1 or 2 rectal prolapse vaginal prolapse beyond the hymen unable to understand informed consent information even with provision of a medical translator

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
Intervention Model: Single Group Assignment
Interventional Model Description: Patients with refractory Fecal Incontinence (FI) will be identified from the Atrium Wake Forest Baptist Health outpatient Gastroenterology, Urogynecology and Colorectal Surgery clinics.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Muscle Fiber Fragment (MFF) injections<br>autologous muscle fiber fragment injections, harvested in an autologous fashion from the quadriceps muscle, for the treatment of Fecal Incontinence (FI) symptoms in men and women with a demonstrated anal sphincter defect and who have failed conservative treatments | Procedure: Muscle Fiber Fragment (MFF) Injections<br>* The participant will be treated with an injection of muscle fiber fragments into the external anal sphincter at 3, 6, 9 and 12 o'clock using a 21-gauge needle to a depth of 1-2 cm from the external skin using equal amounts in each quadrant.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cleveland Clinic Fecal Incontinence Severity Scoring System (CCIS) scores (also termed the Wexner score) | fecal incontinence score from 0-20; where 0 is perfect continence and 20 is complete incontinence | Month 3 | 
| Cleveland Clinic Fecal Incontinence Severity Scoring System (CCIS) scores (also termed the Wexner score) | fecal incontinence score from 0-20; where 0 is perfect continence and 20 is complete incontinence | Month 6 | 
| Cleveland Clinic Fecal Incontinence Severity Scoring System (CCIS) scores (also termed the Wexner score) | fecal incontinence score from 0-20; where 0 is perfect continence and 20 is complete incontinence | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fecal Incontinence Quality of Life (FI-QOL) scores | The Fecal Incontinence Quality of Life Scale is composed of a total of 29 items; these items form four scales: Lifestyle (10 items), Coping/Behavior (9 items), Depression/Self-Perception (7 items), and Embarrassment (3 items). | baseline, Months 3 and 12 | 
| Anorectal Manometry (ARM) Pressure scores | Low resting pressure is defined as <50 mmHg during the anorectal motility exam performed with high-resolution catheter (Given, Atlanta, GA). Normal resting pressures range from 50 to 100 mmHg. A flexible catheter with solid-state pressure transducers is placed in the anal canal and rectum to obtain standard pressure measurements | baseline, Months 3 and 12 | 
| Internal Anal sphincter (IAS) Pressure scores | Typical resting pressure in a healthy volunteer is 40 to 60 mmHg | baseline, Months 3 and 12 | 
| Rectal Anal Inhibitory Reflex (RAIR) Pressure scores | Low resting pressure is defined as <50 mmHg during the anorectal motility exam performed with high-resolution catheter (Given, Atlanta, GA). Normal resting pressures range from 50 to 100 mmHg. A flexible catheter with solid-state pressure transducers is placed in the anal canal and rectum to obtain Rectal Anal Inhibitory Reflex (RAIR) | baseline, Months 3 and 12 | 
| Fecal Incontinence Severity Index (FISI) scores | Participants who score closer to 61 are likely to have their quality of life severely impacted by the fecal incontinence they suffer from. | baseline, Months 3 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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low anal pressures, passive incontinence, bowel movements, sphincter muscle