Intravenous Estrogen in Kidney Transplant Study

NCT03663543 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 82378
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Ischemia perfusion injury (IRI) is a major cause of organ injury during kidney transplantation. 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 supplements. This study will look at the effect of intravenous estrogen given peri-operatively to reduce the effect of IRI in female kidney transplant recipients.

Conditions

Ischemia Reperfusion Injury

Outcome Measures

Primary Outcomes (1)

• Glomerular filtration rate (GFR)

  GFR (glomerular filtration rate) as calculated from a DTPA (Diethylenetriamine Pentaacetic Acid, a medication) renal scan.

  Post-operative day three

Secondary Outcomes (1)

• Delayed graft function (DGF)

  Immediately post-operative

Other Outcomes (3)

• Graft Failure

  Post-operative day three and day ninety

• Post Op Day 3 Creatinine

  Post-operative day 3

• Nadir Post op Day 90 Creatinine

  post transplant day 90

Study Arms (2)

Active Arm

ACTIVE COMPARATOR

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).

Drug: Conjugated Estrogen

Placebo Arm

PLACEBO COMPARATOR

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

Drug: Normal saline

Interventions

Conjugated Estrogen DRUG

Dosing of conjugated estrogen will be given pre kidney transplant procedure and twice after reperfusion of the transplanted kidney.

Also known as: Premarin

Active Arm

Normal saline DRUG

Dosing of normal saline will be given pre kidney transplant procedure and twice after reperfusion of the transplanted kidney.

Also known as: 0.9% sodium chloride

Placebo Arm

Eligibility Criteria

• Age: 21 Years+
• Gender Eligibility Details: Participants must be female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female gender
• Age \> 21 years at time of transplant
• Pre-existing dialysis dependence of at least 1-months duration at the time of transplant
• Receiving a deceased donor renal transplant with KDPI \>40
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study

You may not qualify if:

• History of solid organ transplant
• Receiving a combined heart-kidney transplant, liver-kidney transplant, or other multi-visceral organ transplant
• Personal history of deep vein thrombosis (DVT) or pulmonary embolism (PE)
• Personal history of an estrogen sensitive cancer (breast, endometrial, ovarian)
• Personal history of arterial thromboembolic disease such as stroke or myocardial infarction in the 6 months prior to transplantation
• Patient already on estrogen (including oral contraceptive pills) or anti-estrogen therapy for other indications
• Patient who is expected to not tolerate a dose of 500-5000U intravenous heparin at the time of transplant as determined by the transplant surgeon
• Patient who has a contraindication or allergy to or is expected to not tolerate a dose of 2500-7500U subcutaneous heparin prophylaxis three times daily during hospital stay as determined by the transplant surgeon
• Pregnant and breast feeding patients will be excluded from the study due to the small risk of radiation associated with the DTPA renal scan
• Patient body mass index (BMI) \> 40
• Known anaphylactic reaction and/or angioedema to Premarin Intravenous therapy
• Presence of a condition or abnormality that in the opinion of the investigator or attending transplant surgeon primarily responsible for the patient's care would compromise the safety of the patient or the quality of the data.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (30)

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• Bradley LD, Gueye NA. The medical management of abnormal uterine bleeding in reproductive-aged women. Am J Obstet Gynecol. 2016 Jan;214(1):31-44. doi: 10.1016/j.ajog.2015.07.044. Epub 2015 Aug 5.

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• Murray AW, Barnfield MC, Waller ML, Telford T, Peters AM. Assessment of glomerular filtration rate measurement with plasma sampling: a technical review. J Nucl Med Technol. 2013 Jun;41(2):67-75. doi: 10.2967/jnmt.113.121004. Epub 2013 May 8.

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• Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL. Delayed graft function: risk factors and implications for renal allograft survival. Transplantation. 1997 Apr 15;63(7):968-74. doi: 10.1097/00007890-199704150-00011.

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• Alves MG, Oliveira PJ, Carvalho RA. Substrate selection in hearts subjected to ischemia/reperfusion: role of cardioplegic solutions and gender. NMR Biomed. 2011 Nov;24(9):1029-37. doi: 10.1002/nbm.1640. Epub 2011 Jan 28.

  PMID: 21274961 RESULT

• Ardelt AA, Carpenter RS, Lobo MR, Zeng H, Solanki RB, Zhang A, Kulesza P, Pike MM. Estradiol modulates post-ischemic cerebral vascular remodeling and improves long-term functional outcome in a rat model of stroke. Brain Res. 2012 Jun 21;1461:76-86. doi: 10.1016/j.brainres.2012.04.024. Epub 2012 Apr 21.

  PMID: 22572084 RESULT

• Eckhoff DE, Bilbao G, Frenette L, Thompson JA, Contreras JL. 17-Beta-estradiol protects the liver against warm ischemia/reperfusion injury and is associated with increased serum nitric oxide and decreased tumor necrosis factor-alpha. Surgery. 2002 Aug;132(2):302-9. doi: 10.1067/msy.2002.125718.

  PMID: 12219027 RESULT

• Gabel SA, Walker VR, London RE, Steenbergen C, Korach KS, Murphy E. Estrogen receptor beta mediates gender differences in ischemia/reperfusion injury. J Mol Cell Cardiol. 2005 Feb;38(2):289-97. doi: 10.1016/j.yjmcc.2004.11.013. Epub 2005 Jan 20.

  PMID: 15698835 RESULT

• Peng X, Wang J, Lassance-Soares RM, Najafi AH, Sood S, Aghili N, Alderman LO, Panza JA, Faber JE, Wang S, Epstein SE, Burnett MS. Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia. Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2027-34. doi: 10.1152/ajpheart.00004.2011. Epub 2011 Mar 11.

  PMID: 21398592 RESULT

• Hu H, Wang G, Batteux F, Nicco C. Gender differences in the susceptibility to renal ischemia-reperfusion injury in BALB/c mice. Tohoku J Exp Med. 2009 Aug;218(4):325-9. doi: 10.1620/tjem.218.325.

  PMID: 19638737 RESULT

• Muller V, Szabo A, Viklicky O, Gaul I, Portl S, Philipp T, Heemann UW. Sex hormones and gender-related differences: their influence on chronic renal allograft rejection. Kidney Int. 1999 May;55(5):2011-20. doi: 10.1046/j.1523-1755.1999.00441.x.

  PMID: 10231466 RESULT

• Muller V, Losonczy G, Heemann U, Vannay A, Fekete A, Reusz G, Tulassay T, Szabo AJ. Sexual dimorphism in renal ischemia-reperfusion injury in rats: possible role of endothelin. Kidney Int. 2002 Oct;62(4):1364-71. doi: 10.1111/j.1523-1755.2002.kid590.x.

  PMID: 12234307 RESULT

• Park KM, Kim JI, Ahn Y, Bonventre AJ, Bonventre JV. Testosterone is responsible for enhanced susceptibility of males to ischemic renal injury. J Biol Chem. 2004 Dec 10;279(50):52282-92. doi: 10.1074/jbc.M407629200. Epub 2004 Sep 8.

  PMID: 15358759 RESULT

• Park KM, Cho HJ, Bonventre JV. Orchiectomy reduces susceptibility to renal ischemic injury: a role for heat shock proteins. Biochem Biophys Res Commun. 2005 Mar 4;328(1):312-7. doi: 10.1016/j.bbrc.2004.12.177.

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• Robert R, Ghazali DA, Favreau F, Mauco G, Hauet T, Goujon JM. Gender difference and sex hormone production in rodent renal ischemia reperfusion injury and repair. J Inflamm (Lond). 2011 Jun 9;8:14. doi: 10.1186/1476-9255-8-14.

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• Rusai K, Prokai A, Szebeni B, Meszaros K, Fekete A, Szalay B, Vannay A, Degrell P, Muller V, Tulassay T, Szabo AJ. Gender differences in serum and glucocorticoid regulated kinase-1 (SGK-1) expression during renal ischemia/reperfusion injury. Cell Physiol Biochem. 2011;27(6):727-38. doi: 10.1159/000330081. Epub 2011 Jun 17.

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  PMID: 17336333 RESULT

• Soljancic A, Ruiz AL, Chandrashekar K, Maranon R, Liu R, Reckelhoff JF, Juncos LA. Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury. Am J Physiol Regul Integr Comp Physiol. 2013 Jun 1;304(11):R951-8. doi: 10.1152/ajpregu.00360.2012. Epub 2013 Apr 3.

  PMID: 23552495 RESULT

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  PMID: 15251365 RESULT

• Antus B, Liu S, Yao Y, Zou H, Song E, Lutz J, Heemann U. Effects of progesterone and selective oestrogen receptor modulators on chronic allograft nephropathy in rats. Nephrol Dial Transplant. 2005 Feb;20(2):329-35. doi: 10.1093/ndt/gfh602. Epub 2004 Dec 23.

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• DeVore GR, Owens O, Kase N. Use of intravenous Premarin in the treatment of dysfunctional uterine bleeding--a double-blind randomized control study. Obstet Gynecol. 1982 Mar;59(3):285-91.

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MeSH Terms

Conditions

Reperfusion Injury

Interventions

Estrogens, Conjugated (USP); Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Matthew Levine, MD, PhD

  University of Pennsylvania Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel: Participants are assigned to one of two or more groups in parallel for the duration of the study

Study Record Dates

• First Submitted: August 27, 2018
• First Posted: September 10, 2018
• Study Start: August 26, 2016
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)