Implantation Of Vaginal Construct For Patients With Vaginal Aplasia

Study Overview
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Brief Summary
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In this Phase 1, single site, clinical trial, Vulvar/vaginal Smooth muscle cells (SMC) and Epithelial Cells (EPC) are isolated from autologous patient's biopsy

Detailed Description
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The cells are expanded in vitro and seeded on scaffold and matured - The final Tissue Engineered Vagina (TEV) is implanted into the native vaginal site

Official Title
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Phase 1 Trial Of Implantation Of Vaginal Construct For Patients With Vaginal Aplasia

Conditions
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Congenital Mullerian Duct Anomaly

Intervention / Treatment
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* Biological: biologic vaginal-construct implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with congenital Mullerian duct anomaly that includes absence or obliteration of all or part of the vagina, as confirmed on pelvic MRI Females between the ages of 15 and 45 years Patients with stable medical comorbidities Patients that are willing to comply with all study instructions and are willing to return for study follow-up visits Exclusion Criteria: Patients with a history of surgery in the target area more recent than the last 6 months Patients with an active vaginal area infection or urinary infection as evidenced by clinical exam or culture result Patients with a history of keloid scarring Patients who are currently taking anti-platelet medications or blood thinners Patients with a history of clotting disorder Patients with autoimmune disease or immune disorder Patients requiring concomitant use of or treatment with immunosuppressive agents Patients with a history of systemic conditions, including but not limited to HIV, thrombocytopenia, uncontrolled diabetes and chronic liver disease (including Hepatitis B or C), that the Investigator believes may jeopardize the safety of the patient to participate in the study Patients with evidence or diagnosis of any primary coagulation disorder (including concomitant anticoagulation therapy at enrollment) Patients who have been treated with any other investigational drug or participated in any investigational study within 30 days prior to enrollment in this study Patients with neurological disorders (e.g., multiple sclerosis, Parkinson's disease) Patients who are current tobacco users Patients with alcohol/drug abuse problems Patients with any systemic disease Patients with any psychiatric disorders Inability to participate in all necessary study activities due to physical or mental limitations. Any circumstance in which the investigator deems participation in the study is not in the subject's best interest The following vital sign cut-off values, laboratory cut-off values and ECG reading will be monitored as the exclusion criteria in the biopsy visit and again before the implantation surgery BP systolic >160 or <90 millimeters of mercury (mmHg) or diastolic >100 or<60 millimeters of mercury (mmHg) Pulse <60 or >105bpm Respiratory Rate < 9 and >20 Temp > 100.4 degrees Fahrenheit Liver enzymes >2 times the upper limit of normal (ULN) Abnormal bilirubin unless subject has Gilbert's glomerular filtration rate (eGFR) < 60 mL/min/ 1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) HbA1C > 8% Hb <10 mg/dL Platelet Count <100,000 O2 saturation <95% If a vital sign or lab value results in exclusion, the subject could be rescreened later

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

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: Ten women, ages 15-45 years, meeting criteria will undergo vaginal/vulva biopsy and biologic vaginal-construct implantation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: autologous vaginal construct for patients with vaginal aplasia<br>Biologic vaginal construct, surgically implanted into native vaginal site | Biological: biologic vaginal-construct implantation<br>* biologic Tissue Engineered Vagina (TEV), which provides an epithelial layer for the luminal aspect and a smooth muscle layer for protecting the openness of the hollow tube, mimicking the cellular orientation and architecture of the vagina. Autologous cells isolated from vagina/vulva remnants offset any potential for immunological rejection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Serious Adverse Events | bleeding, pain, visceral injury, vaginal scarring, contraction, or infection | Month 36 | 
| Quality of Life Scores | The Quality of Life Scores (QOLS) is scored by adding up the score on each item to yield a total score for the instrument. Scores can range from 16 to 112 - the higher score indicates the higher quality of life | Baseline | 
| Quality of Life Scores | The Quality of Life Scores (QOLS) is scored by adding up the score on each item to yield a total score for the instrument. Scores can range from 16 to 112 - the higher score indicates the higher quality of life | Month 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of life Female Sexual Function Index (FSFI) Scores | The Female Sexual Function Index (FSFI) is a multidimensional measure of female sexual functioning with 19 items that have ordinal, Likert- type response formats and are scored from 0 (or 1) to 5. The scoring algorithm sums items on each domain/sub-scale and then scales the sums so that each subscale has a maximum score of 6 - The FSFI is a survey measuring the sexual functioning of women in six different domains: desire, arousal, lubrication, orgasm, satisfaction and pain - Higher scores indicate better functioning | Month 3, Month 6, Month 12, and Month 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaginal Abnormality