Surgical Evaluation of Using the Prepuce in Feminizing Genitoplasty
Primary Purpose
Congenital Adrenal Hyperplasia
Status
Unknown status
Phase
Not Applicable
Locations
Egypt
Study Type
Interventional
Intervention
feminizing genitoplasty using inner surface of the prepuce as pedicled tubularized flap
Sponsored by
About this trial
This is an interventional treatment trial for Congenital Adrenal Hyperplasia focused on measuring congenital adrenal hyperplasia, Feminizing genitoplasty, Vaginal stenosis
Eligibility Criteria
Inclusion criteria:
- Females (46, XX genotype identified by karyotype
- Age: infants and children from 18 months old age to 14 years
- Virilized external genitalia.
- Persistent urogenital sinus
- Congenital adrenal hyperplasia.
- Controlled by glucocorticoid and mineralocorticoid replacement therapy and clinically and hormonally judged fit for surgical interventions.
- Voluntarily provided informed written consent of the parents for the planned procedure and possible risks.
- Informed written approval of the parents of the included children to use clinical data collected in a research program.
Exclusion Criteria:
- Male disorders of sexual development (46 XY)
- Debatable sex of rearing; Mixed gonadal dysgenesis, Ovotesticular disorders of sexual development and partial androgen insensitivity syndrome.
- Inadequate compliance with corticosteroid therapy, rendering surgery or interventions clinically hazardous or unsuitable.
- Inadequately controlled hormonal assay: elevated androgens.
- Patients who did any corrective surgery before.
Sites / Locations
- faculty of medicine- Cairo UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
feminizing genitoplasty using inner surface of the prepuce
Arm Description
Feminizing genitoplasty will be done using the prepuce as a pedicled tubularized flap to create the new vagina, the new vagina which the investigators create it from the prepuce will be sutured above to the native vagina after its separation from the urogenital sinus, and the remaining part of the urogenital sinus will be used to create the urethra, the remaining part of the prepuce will create the labia minora, clitoroplasty will be attempted in all patients.
Outcomes
Primary Outcome Measures
vaginal size calibration
the new vagina will be assessed for stenosis 1 month after the procedure using Hegar dilators under general anaesthesia, further calibration will be done over 6 months to ensure patency of the vagina and to avoid stenosis by dilatation if stenosis encountered
Secondary Outcome Measures
urinary incontinence
in patient older than 3 years and complaining from incontinence, urodynamics will be done.
Full Information
NCT ID
NCT03897504
First Posted
March 28, 2019
Last Updated
December 28, 2019
Sponsor
Kasr El Aini Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03897504
Brief Title
Surgical Evaluation of Using the Prepuce in Feminizing Genitoplasty
Official Title
Surgical Evaluation Of Using The Inner Surface Of The Prepuce In Feminizing Genitoplasty In Cases Of Verilized Females With Congenital Adrenal Hyperplasia
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Unknown status
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
January 1, 2020 (Anticipated)
Study Completion Date
January 1, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Kasr El Aini Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Background and Rationale: The vaginoplasty remains a challenge for the surgeon. The most commonly used techniques have been: the Y-V plasty described by fortunoff for low vagina, the pullthrough operation described by Hendren and Crawford for high vagina, and the passerini-Glazer technique . None of these procedures is entirely satisfactory; with the first two, the neovagina has a tendency to become stenotic in most cases. Moreover, in the third, in addition to the high rate of stenosis, which is encountered in a third of case , the high rate of urethro-vaginal fistulas is unacceptable
Objectives :
To describe and evaluate a surgical technique for vaginoplasty that is easy to realize with fewer complications especially vaginal stenosis.
Study population & Sample size : 24 patients suffering from congenital adrenal hyperplasia (CAH) presenting to outpatient clinic of diabetis Endocrine And Metabolism Pediatric Unit (DEMPU) of Cairo University Specialized Pediatric Hospital will be considered.
Study Design : non-controlled prospective clinical trial with all patients included in single group
Methods: Cystoscopy will be done promptly before proceeding to surgery, Confluence depth more than 20 mm is considered high anomaly, feminizing genitoplasty will be done as a one-stage procedure, One month after operation, examination under anesthesia will be done with calibration of vagina.
Possible Risk (s) to study population : The risk of this study is involving a vulnerable group of females which exposed to lengthy operation may complicate with bleeding and need for blood transfusion, infection early after surgery or vaginal stenosis.
Outcome parameter (s):
Vaginal calibration using hegars dilators Urodynamics for females older than 3 years and complaining from incontinence
Detailed Description
• Background and Rationale: Disorders of sex development(DSD) are medical conditions in which the development of chromosomal, gonadal, or anatomic sex varies from normal and may be incongruent with each other. Five main groups of DSD patients may be identified, submitted to the gender assignment process, and may be considered for a surgical genital reconstruction. (Lee Pa et al, 2006) Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive disorders resulting from deficiency of one of the five enzymes required for synthesis of cortisol in the adrenal cortex. CAH is the most common cause of genital ambiguity. (van der Zwan, 2013) About 90-95% of individuals with CAH have a mutation in CYP21A2 gene, encoding 21-hydroxylase enzyme. The worldwide incidence of classical 21 OHD is 1:15,000 to 1:16,000 live births of which approximately 75% are salt wasters. That leads to a block of normal production of cortisone and results in overproduction of steroid metabolism by-products through pituitary feedback. These androgenic steroids lead to a variable degree of masculinization of normal female fetus.
The goal of therapy in CAH is to both correct the deficiency in cortisol secretion and suppresses adrenocorticotropic hormone (ACTH) overproduction. Proper treatment with glucocorticoid reduces stimulation of the androgen pathway, thus preventing further virilization and allowing normal growth and development. In addition to hormonal therapy, feminizing reconstructive surgery targets the correction of anatomical disturbance. The feminizing genitoplasty operation consists of reducing the size of the phallus (clitoroplasty), creating labia minora and vaginoplasty.
• Sample size: Sample size calculation: n = 2(Za+Z1-β)2σ2/Δ2 n sample size Za = 1.65 ( p<0.05 as acceptable and a study with 80% power; using the below table, we get the following values: Zα, is 1.65 a error 5% 1% .1% 2 sided 1.96 2.5758 3.2905
1 sided 1.65 2.33 Z1-,β= 0.8416 power 80% 85% 90% 95% value 0.8416 1.0364 1.2816 1.6449 σ standard deviation =0 .5 Δ effect size 36% =0.36 Effect of using the prepuce in minimizing vaginal stenosis is 100% - effect of using other techniques 64%
N =2(1.65+0.8416)2 0.52 / 0.362 = 24 patients.
• Study Design: non-controlled prospective clinical trial with all patients included in single group.
Ethical committee approval : approved (N-100-2018)
Study Methods
Population of study & disease condition:
24 patients suffering from congenital adrenal hyperplasia (CAH) presenting with virilized external genitalia to outpatient clinic of diabetes Endocrine And Metabolism Pediatric Unit (DEMPU) of Cairo University Specialized Pediatric Hospital will be considered.
Methodology in details :
Patient recruitment females with congenital adrenal hyperplasia presenting with persistent urogenital sinus and virilized external genitalia to the outpatient clinic of Diabetes Endocrine And Metabolism Pediatric Unit (DEMPU) of Cairo University Specialized Pediatric Hospital
Pre-operative management History taking laying stress on age at diagnosis, family history of similar conditions and consanguinity in addition to any salt losing events.
Reviewing the patients charts for the investigations (basal adrenal precursors, karyotype, pelvic ultrasound) Complete genital examination to detect the degree of virilization (number and types of openings, the presence of rugae or pigmentation, phallus size and Prader scale).
Routine pre-operative blood tests will be done .
Perioperative hormonal therapy in the form of hydrocortisone and/or fludrocortisone in conjunction with pediatric anesthesia and pediatric endocrinology teams including dose adjustment and electrolytes follow up.
Genitography: Patient is generally anesthetized either in same setting of surgery or pre-operatively in different setting, The depth of confluence from perineal marker is measured in ratio to perineal marker dimensions whatever the scale of genitography picture is, then measurements are taken in millimeters. Other measurements of proximal urethra and vagina to the confluence are taken.
Operative technique Cystoscopy will be done promptly before proceeding to surgery in the same setting.
Confluence depth more than 20 mm is considered high anomaly with consequent difficult and lengthy procedure with high probability of need to use vaginal pullthrough in combination with the use of inner layer of the prepuce.
feminizing genitoplasty will be done as a one-stage procedure. The patient is placed in the lithotomy position for the best exposure of the perineum. A Foley catheter French 6 is placed in the vagina to facilitate identification of structures during dissection, The clitoroplasty will be attempted in all Cases.
The dissection of the flap from the inner surface of the prepuce with its pedicle will be done after measuring the distance between the native vagina and perineum. and then tubularized onto a rectal stent (French 12 or 14).
The proximal edge of the preputial flap will be sutured to upper vagina and its distal edge to outer edge. The rectal drain will be left in the vagina for 5 days postoperatively, by this technique the vaginoplasty can be achieved without further mobilization of the vagina which may affect the continence of the patient if we divide pubourethral ligament, labia this procedure will be followed by clitoroplasty and labioplasty.
In cases of low urogenital sinus (less than 2 cm), the use of preputial flap alone is often sufficient.
in case of high confluence additional procedure will be done in the form of laparoscopic vaginal pull-through
Postoperative management:
Wound will be closed by x-shaped bandage for 24 hours.
Vitamin K, ethamsylate (dicynone) and tranexamic acid (cyklokapron) will be given to help in hemostasis.
After dressing removal the wound will be left exposed and flushed with sterile -saline every 4-6 hours
Urinary catheter and vaginal stent will be removed on 5th to 7th day post operatively.
Parenteral broad spectrum antibiotics and antianaerobes will be given for one week. Stress doses of steroids will be continued for 2-3 days after surgery at double usual oral dose followed by tapering and returning to the original dose
postoperative management: One month after operation, examination under anaesthesia will be done with calibration of vagina using Hegar dilators and making decision for further need for repeated vaginal dilatation.
Urodynamics will be applied for patients older than 3 years old to asses the continence in cases with high confluence.
Primary outcome:
To calibrate the vagina and asses the degree of vaginal stenosis if present and need for further vaginal dilatation.
Secondary outcome:
To asses other outcomes specially the continence in patients older than 3 years old and the prescence of urethrovaginal fistula.
Short term complications:
Infection at vestibule and incision lines
accidental removal of the catheter
haematoma
secondary haemorrage
Intermediate and long term complications:
urethrovaginal fistula
recurrent persistant urogenital sinus (UGS)
Vaginal stenosis
Urinary incontinence
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Adrenal Hyperplasia
Keywords
congenital adrenal hyperplasia, Feminizing genitoplasty, Vaginal stenosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
feminizing genitoplasty using inner surface of the prepuce
Arm Type
Experimental
Arm Description
Feminizing genitoplasty will be done using the prepuce as a pedicled tubularized flap to create the new vagina, the new vagina which the investigators create it from the prepuce will be sutured above to the native vagina after its separation from the urogenital sinus, and the remaining part of the urogenital sinus will be used to create the urethra, the remaining part of the prepuce will create the labia minora, clitoroplasty will be attempted in all patients.
Intervention Type
Procedure
Intervention Name(s)
feminizing genitoplasty using inner surface of the prepuce as pedicled tubularized flap
Intervention Description
the prepuce of the females with congenital adrenal hyperplasia will be tubularized and used as pedicled flap in creating the new vagina, the urethra will be completed with the urogenital sinus, no mobilization either partial or complete urogenital mobilization will be needed in cases with low and intermediate confluence level (less than 30 mm), in case with high confluence (more than 30 mm) laparoscopic vaginal pullthrough will be attempted first then the same previously described technique will be applied, the depth of the confluence will be determined before starting surgery by doing genitograph under general anaesthesia, stent will be kept in the new vagina for 5 days and further scheduled calibrations and dilatations will be applied regularly with paying attention to urinary complications like incontinence and urethrovaginal fistula by doing urodynamics and micturating cystourethrogram if there is a complain.
Primary Outcome Measure Information:
Title
vaginal size calibration
Description
the new vagina will be assessed for stenosis 1 month after the procedure using Hegar dilators under general anaesthesia, further calibration will be done over 6 months to ensure patency of the vagina and to avoid stenosis by dilatation if stenosis encountered
Time Frame
6 months to one year
Secondary Outcome Measure Information:
Title
urinary incontinence
Description
in patient older than 3 years and complaining from incontinence, urodynamics will be done.
Time Frame
6 months
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
the study applicable only in over virilized females with congenital adrenal hyperplasia
Minimum Age & Unit of Time
18 Months
Maximum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Females (46, XX genotype identified by karyotype
Age: infants and children from 18 months old age to 14 years
Virilized external genitalia.
Persistent urogenital sinus
Congenital adrenal hyperplasia.
Controlled by glucocorticoid and mineralocorticoid replacement therapy and clinically and hormonally judged fit for surgical interventions.
Voluntarily provided informed written consent of the parents for the planned procedure and possible risks.
Informed written approval of the parents of the included children to use clinical data collected in a research program.
Exclusion Criteria:
Male disorders of sexual development (46 XY)
Debatable sex of rearing; Mixed gonadal dysgenesis, Ovotesticular disorders of sexual development and partial androgen insensitivity syndrome.
Inadequate compliance with corticosteroid therapy, rendering surgery or interventions clinically hazardous or unsuitable.
Inadequately controlled hormonal assay: elevated androgens.
Patients who did any corrective surgery before.
Facility Information:
Facility Name
faculty of medicine- Cairo University
City
Cairo
State/Province
El Manial
ZIP/Postal Code
12613
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mahmoud T Mohammed, assistan lecturer
Phone
01111830411
Ext
002
Email
Mahmoud.tarek@kasralainy.edu.eg
First Name & Middle Initial & Last Name & Degree
Ahmed K weshahi, lecturer
Phone
01095227442
Ext
002
Email
ahmed.kadry@kasralainy.edu.eg
First Name & Middle Initial & Last Name & Degree
Hesham M Elsaket, professor
First Name & Middle Initial & Last Name & Degree
khaled H Bahaa Eldin, professor
First Name & Middle Initial & Last Name & Degree
Hend M Abdel Latif, professor
First Name & Middle Initial & Last Name & Degree
Ahmed K Weshahi, lecturer
First Name & Middle Initial & Last Name & Degree
Mahmoud T Mohamed, assistant lecturer
12. IPD Sharing Statement
Learn more about this trial
Surgical Evaluation of Using the Prepuce in Feminizing Genitoplasty
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