End Stage Renal Disease (ESRD), Hypogonadism, Male, Kidney Transplant
Conditions
Keywords
ESRD, testosterone replacement therapy, hypogonadal, kidney transplant
Brief summary
This prospective study aims to evaluate the safety and efficacy of testosterone replacement therapy (TRT) as an adjunct to an enhanced recover after surgery (ERAS) protocol in men with end-stage renal disease (ESRD) undergoing kidney transplantation. Participants will be highly-listed hypogonadal men, defined as total testosterone level \<300 on two occasions with clinical symptoms of hypogonadism, with ESRD who are expected to receive a kidney transplant within 6 months. Participants will be started on TRT, ideally for at least 3 months prior transplantation. The investigators will perform a subset analysis to evaluate if there is a significant difference in our endpoints by comparing these two subgroups (Three months or more receiving TRT vs. Less than three months receiving TRT). There will be no cut-off time for pre-transplant TRT. Following the intervention period, a historical control cohort of age-matched and health-matched patients will be identified, who have followed a standard transplant protocol that does not incorporate TRT. The primary outcome will evaluate safety, including 30- and 90-day adverse events, 3, 6, and 12-month allograft survival, and overall patient survival. Secondary outcomes will focus on (1) qualitative assessments of symptoms using validated questionnaires, (2) quantitative improvements in the hormonal profile before and after initiation of TRT and surgery, and (3) allograft function and incidence of delayed graft function. The results of this study could provide novel insights into the benefits of TRT in improving surgical outcomes in men with ESRD undergoing kidney transplantation.
Interventions
DRUGTestosterone Replacement Therapy
Testosterone Replacement Therapy
Sponsors
University of California, Los Angeles
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male patients older than 18 years old with confirmed end-stage renal disease (ESRD). * Hypogonadal (testosterone level \<300 ng/dL) with clinical symptoms of hypogonadism. * Expected to undergo kidney transplantation within a 6-month period. * Able and willing to comply with study procedures and follow-up visits.
Exclusion criteria
* Women or non-hypogonadal men. * Any contraindications to testosterone therapy, including: * History of Breast Cancer * Severe untreated OSA * Polycythemia (Hct \>54%) * Uncontrolled chronic heart failure (CHF) * A history of a Major Adverse Cardiac Event (MACE) within the past 6 months * Interest in fertility within 1 year * An unevaluated PSA \>4.0 ng/mL or a PSA \>3.0 ng/mL in individuals with risk factors for prostate cancer defined as: * Men with African ancestry * Men with first-degree relative with prostate cancer * Known genetic mutations including BRCA1/2 * A history of Lynch Syndrome * Abnormal DRE * Participants already receiving testosterone or other androgen therapies. * Severe cardiovascular or pulmonary conditions that pose a high surgical risk. * Any condition that, in the opinion of the investigator, would make the subject ineligible for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 18 months | Complications categorized by the CTCAE classification (grades 1-5) |
| Overall Survival | 18 months | measured as a rate |
| Death-Censored- Graft Survival | 18 months | Graft Survival will be the duration from transplantation until graft failure. Graft failure defined as (1) resumption of dialysis (2) allograft removal or (3) need for retransplantation/relisted on the transplant list |
| Healthcare Utilization Metrics | 18 months | Hospital readmission rates |
| Length of hospitalization | 18 months | days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Testosterone Panel | Every 3 months after starting TRT; at the time of transplantation; 30-, 90-, 180-, 270-, and 360-days post transplantation | Total, Free, and Bioavailable Testosterone Levels, measured as ng/dL |
| Prostate Specific Antigen (PSA) | at baseline prior to TRT therapy, and every 3-6 months during active hormone therapy. | ng/mL |
| Luteinizing Hormone (LH) | Once prior to initiation of TRT surgery | mIU/mL |
| Prolactin | Once prior to initiation of TRT surgery | ng/mL |
| Serum Creatinine Levels | At 3-, 6-, and 12-months post-transplantation | measured as mg/dL |
| Hematocrit | 1 month after TRT initiation, and at 3-, 6-, and 12-month intervals | To assess for polycythemia, measured as L/L, read as a percentage |
| Muscle Body Composition Analysis | at time of consent, 30 days, 180-days, and 360 days after transplantation | SECA Body Analysis is a non-invasive scan measuring BMI, Fat-Mass Index, Fat Mass Percentage, Skeletal Muscle Mass, and Skeletal Muscle Mass Percentage |
| Qualitative Assessment of Hypogonadal Symptoms | at time of consent; every 3-6 months starting TRT; 30- and 90-days following transplantation | qADAM is a validated questionnaire of 10 questions to assess hypogonadal symptoms |
| Hemoglobin | 1 month after TRT initiation, and at 3-, 6-, and 12-month intervals | To assess for polycythemia, measured as g/dL |
| estimated glomerular filtration rate (eGFR) | At 3-, 6-, and 12-months post-transplantation | ml/min/1.73 m\^2 |
| Rate of delayed graft function | 1 week following transplant | Defined as the need for dialysis within the first week post-transplant. |
| Tacrolimus trough level | 1 month after TRT initiation, and at 3-, 6-, and 12-months post-transplant | ng/mL |
| Follicle-Stimulating Hormone (FSH) | Once prior to initiation of TRT surgery | mIU/mL |
Countries
United States
Outcome results
None listed