Vascularized Composite Allotransplantation (VCA) for Devastating Penile and Concomitant Genital Trauma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Need for Immunosuppressive drug therapy
研究概览
简要总结
This is a 4-year, non-randomized, single center, patient self-controlled, clinical trial (though enrolled subjects will be followed for life as are all transplant patients) for patients seeking allotransplantation of the male external genitalia (MEG), or penile tissue, as a feasible reconstructive strategy for the treatment of devastating and irreversible injuries to the genitalia. In addition to receiving penile allotransplantation and post-operative monitoring and support, enrolled patients will receive an innovative and clinically proven immunomodulatory protocol that combines lymphocyte depletion of the recipient with donor bone marrow cell infusion. Patients will be treated with lymphocyte depleting induction therapy, donor bone marrow cell infusion and tacrolimus. After the first year, maintenance immunosuppression will be modified gradually and cautiously (tapered dose reduction or spaced frequency dosing of tacrolimus) in selected patients based on a critical evaluation of clinical and immunologic outcomes. Outcomes will include but not be limited to functional metrics (sensation, erection, voiding), psychosocial (body integrity, adaptation to transplant) and health related quality of life (HRQOL) measures.
详细描述
Initial treatment with an antibody targeting recipient immune cells followed by triple-drug maintenance therapy represents the current standard in clinical VCA. Our protocol is different from the existing conventional drug treatments used in MEG allotransplantation in that it combines donor bone marrow infusion with an immunosuppression sparing protocol. The primary goal of this pilot clinical trial is to determine the feasibility of using allogeneic penile tissue to repair/replace irreversibly damaged external genitalia. Enrolled and transplanted subjects will be followed for their lifetime as a transplant patient.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •For Recipients
- •18-40 years
- •Irreversible and devastating genitalia damage not amenable to conventional reconstruction.
- •Patent main vessels leading into the remaining penile stump, as confirmed by angiography.
- •Adequate penile stump (> 2.5cm) to facilitate placement of a tourniquet, debridement of the distal portion and sufficient distal mobilization of the structures requiring anastomosis
- •Eligible for long term standard of care coverage
排除标准
- •For Recipients
- •Documented history of:
- •renal impairment
- •hepatic disorders
- •neurologic disorders (sensory or motor function deficits)
- •severe scarring with poor host tissue bed
- •penile resection or implant surgery
- •hypertension
- •hyperlipidemia
- •coronary artery disease
- •untreated genital cancer
- •HIV, Hepatitis B or C, or any infectious disease
- •erectile dysfunction
- •Peyronie's disease
- •urethral stricture disease
- •xerotica obliterans
- •pelvic embolization
- •pelvic radiation
- •untreated hypogonadism
- •prior prostate surgery
- •recurrent urinary tract infections (UTIs)
- •nephrolithiasis
- •connective tissue disease or collagen disease
- •lipopolysaccharidosis or amyloidosis
- •Use of 5-alpha-reductase inhibitors
- •External signs, sequelae or positive serology of sexually transmitted disease (including HPV)
- •Active UTI, stones, urethral edema and other pathology that prevents urethral anastomosis
- •Current or past substance abuse
- •Current or past smoker (within past 3 months)
- •Use of any medications known to cause vasoconstriction
- •Psychiatric illness or psychological problems, or deemed unsuitable on psychiatric evaluation
- •Any condition that may prevent transplantation (positive cross match, high panel reactive antibody (PRA), etc.)
- •Uncontrolled bleeding disorder, platelet count > 50,000, hemophilia or any other inherited coagulopathy or need to routinely receive blood products for bleeding disorders
- •Concurrent participation in any other clinical investigation during the period of this investigation
- •Inability to undergo leukapheresis
- •Inability to participate in all necessary study activities due to physical or mental limitations
- •Inability or unwillingness to return for all required follow-up visits.
- •Inability or unwillingness to sign the patient informed consent document.
研究组 & 干预措施
Penile Allotransplant and Immunosuppression Treatment
Penile transplantation with monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.
干预措施: Penile Transplant (Procedure)
Penile Allotransplant and Immunosuppression Treatment
Penile transplantation with monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.
干预措施: Monoclonal Antibody (Humanized Anti-CD52) (Biological)
Penile Allotransplant and Immunosuppression Treatment
Penile transplantation with monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Need for Immunosuppressive drug therapy
时间窗: 6 months
The amount of immunosuppressive drug therapy will be recorded.
次要结局
- erectile function(6 months)
- Assessment of sensory return and sensory thresholds(6 months)
- Determination of hemodynamic status(6 months)
- The Reintegration to Normal Living (RNL) Index(6 months)
- The Situational Inventory of Body-Image Dysphoria (SIBID)(6 months)
- The Function and Body Image Survey(6 months)