Estrogen for Reperfusion Injury in Kidney Transplant Patients

(PERT Trial)

Overseen By Julia Lewandowski

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: University of Pennsylvania

Must not be taking: Estrogen, Anti-estrogen

Disqualifiers: History of transplant, Hypercoagulable conditions, Estrogen sensitive cancer, others

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether conjugated estrogen can reduce ischemia perfusion injury, a type of organ damage common during kidney transplants. Researchers found that female mice benefited from estrogen, prompting tests in female kidney transplant recipients. Participants will receive either estrogen or a placebo to determine if estrogen protects the transplanted kidney. The trial seeks women who have been on dialysis for at least a month and are receiving a kidney from a deceased donor. As a Phase 1, Phase 2 trial, this research aims to understand the treatment's mechanism and measure its effectiveness in an initial group, offering participants the opportunity to contribute to advancements in kidney transplant care.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are already on estrogen or anti-estrogen therapy, you cannot participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that conjugated estrogen might be a safe option for kidney transplant patients. Studies in female mice have found that estrogen supplements can protect against ischemia reperfusion injury (IRI), a type of damage that occurs when blood flow returns to the kidney after a transplant. These findings suggest that conjugated estrogen could help reduce this damage in humans as well.

Conjugated estrogen is already used for other health conditions, providing some confidence in its safety. Studies in various contexts have generally found it to be well-tolerated. However, as this research is still in the early stages, further studies are needed to confirm its safety specifically for kidney transplants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using conjugated estrogen for reperfusion injury in kidney transplant patients because it offers a novel approach compared to traditional treatments like immunosuppressants. Unlike standard options that primarily focus on suppressing the immune response to prevent rejection, conjugated estrogen targets the inflammatory damage that can occur when blood flow returns to the transplanted kidney, a process known as reperfusion injury. This treatment could potentially protect the kidney from early damage, improving its function and longevity. Additionally, the timing and method of infusion are designed to maximize the protective effects right when the kidney is most vulnerable, offering a proactive measure that standard treatments don't address.

What evidence suggests that conjugated estrogen might be an effective treatment for ischemia perfusion injury in kidney transplant patients?

This trial will compare the effects of conjugated estrogen with a placebo in kidney transplant patients. Research has shown that estrogen might protect the kidneys from damage when blood flow returns after a transplant, a problem known as ischemia reperfusion injury (IRI). Studies with female mice found that short-term estrogen supplements can lessen this type of damage. Estrogen appears to work by influencing a specific process in the body that helps reduce kidney damage. Although most evidence comes from animal studies, these findings suggest that estrogen could benefit women undergoing kidney transplants by reducing injury during the procedure. ^{1 2 6 7 8}

Who Is on the Research Team?

Matthew Levine, MD, PhD

Principal Investigator

University of Pennsylvania Health System

Are You a Good Fit for This Trial?

This trial is for women over 21 years old who have been on dialysis for at least a month and are about to receive a kidney transplant from a deceased donor. They must be able to follow the study's procedures and not have any history of blood clots, estrogen-sensitive cancers, recent heart attacks or strokes, previous organ transplants, or be on hormone therapies.

Inclusion Criteria

I have been on dialysis for at least 1 month before my transplant.

I am female.

Written informed consent obtained from subject and ability for subject to comply with the requirements of the study

Exclusion Criteria

You have experienced a severe allergic reaction or swelling to Premarin Intravenous therapy.

I have had cancer that is sensitive to estrogen like breast, endometrial, or ovarian cancer.

Pregnant and breast feeding patients will be excluded from the study due to the small risk of radiation associated with the DTPA renal scan

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Peri-operative Treatment

Participants receive a single infusion of conjugated estrogens at the time of admission or approximately 8 hours before surgery, followed by two daily infusions post-transplant

2 days

In-hospital treatment

Immediate Post-operative Monitoring

Participants are monitored for delayed graft function and creatinine levels immediately post-operative and on post-operative day three

3 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including creatinine levels on post-operative day ninety

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Conjugated Estrogen
• Normal saline

Trial Overview The study tests if intravenous estrogen given around the time of surgery can reduce kidney damage from ischemia reperfusion injury in female recipients of kidney transplants. Patients will either receive conjugated estrogen or normal saline as part of their treatment.

How Is the Trial Designed?

Group I: Active Arm Active Control 1 Intervention

Participants randomized to the active arm will receive a single infusion of conjugated estrogens at the time of admission if within 8 hours of the expected surgery time or at approximately 8 hours to the expected surgery time if admission is earlier than that. Participants will then receive two daily infusions of conjugated estrogens after transplant given at 8 hours after reperfusion of the transplanted kidney and 24 hours after the first post transplant dose (32 hours after reperfusion of the transplanted kidney).

Group II: Placebo Arm Placebo Group 1 Intervention

Participants randomized to the placebo arm will receive normal saline (0.9% sodium chloride) at the same rate as the active arm.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Citations

1. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT03663543?keyword=%22Reperfusion%22

Intravenous Estrogen in Kidney Transplant Study Because DGF after kidney transplantation is associated with inferior transplant outcomes and increased costs,2 a therapy that mitigates the effect of IRI ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03663543

Intravenous Estrogen in Kidney Transplant Study Dosing of conjugated estrogen will be given pre kidney transplant procedure and twice after reperfusion of the transplanted kidney. Other Names: Premarin.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8907449/

Estradiol Ameliorates Acute Kidney Ischemia-Reperfusion ... The findings of this study suggest that renal IRI is closely related to the TGF-βRI-SMAD pathway in females and that E 2 exert its protective effect.

4. withpower.com withpower.com/trial/phase-2-reperfusion-injury-7-2016-5f214

Estrogen for Reperfusion Injury in Kidney Transplant Patients Research suggests that estrogen can help protect against kidney damage that occurs when blood supply returns to the kidney after a transplant. This protective ...

5. frontiersin.org frontiersin.org/journals/transplantation/articles/10.3389/frtra.2025.1595766/full

Males and females respond differently to treatment during ... This study aims to evaluate treatment with E2 and MP during isolated perfusion of kidneys in brain-dead male and female rats.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8018493/

Estrogen and estrogen receptors in kidney diseases - PMC Ischemia reperfusion injury in kidney transplantation: a case report. ... Improved renal ischemia tolerance in females influences kidney transplantation outcomes.

7. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT03663543/

Trial | NCT03663543 Currently there are no treatments for IRI other than dialysis. Preliminary studies in female mice have found protection from IRI when given short term estrogen ...

8. europepmc.org europepmc.org/article/pmc/pmc8907449

Estradiol Ameliorates Acute Kidney Ischemia-Reperfusion ... The findings of this study suggest that renal IRI is closely related to the TGF-βRI-SMAD pathway in females and that E 2 exert its protective effect.