Thyroxine Replacement in Organ Donors

Condition(s) targeted: Brain Death

Intervention: L-thryoxine (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Lawson Health Research Institute

Official(s) and/or principal investigator(s):
Michael D Sharpe, MD FRCPC, Principal Investigator, Affiliation: London Health Sciences Centre-UC+

Overall contact:
Michael D Sharpe, MD FRCPC, Phone: 519-663-3030, Email: michael.sharpe@lhsc.on.ca

To compare oral versus intravenous administration of thyroid hormone: 1) for reversibility of hemodynamic instability in organ donors, and, 2) the pharmacokinetics of oral vs iv thryoid administration

Official title: Efficacy and Pharmacokinetics of Oral Thyroid Replacement Therapy in Organ Donors

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Efficacy Study

Primary outcome: Percentage of time patients require inotropic support prior to organ procurement.

Secondary outcome:

1. pharmacokinetic profiles of oral vs iv T3,T4

2. number of organs donate

3. thryoid function derangements at time of brain death

Detailed description: Disruption of the hypothalamic-pituitary axis following brain death may lead to hemodynamic instability, peripheral vasodilation, and diabetes insipidus in organ donors, requiring the use of high doses of inotropes. Inotropes may cause ischemic injury to organs and intramyocardial ATP stores, resulting in organs unsuitable for transplantation, as well as, a reduction in post-transplant organ function. Therefore, some clinicians advocate the use of triple hormonal therapy in potential organ donors.

Since intravenous T3(the intracellular active form of thyroxine) is unavailable, oral or intravenous T4 must be used, requiring the conversion of T4 to T3at the cellular level. This conversion is impeded by glucocorticoids which also are administered to organ donors for their immunomodulating effects. Since oral T3 is readily available, our first question is whether oral versus intravenous administration of T4 is comparable. If so, our next study is to determine the efficacy of oral T3 versus oral T4. Our hypothesis is oral T3 is superior to oral T4.

Our study therefore will determine whether or not the oral route is suitable for administration of thyroid replacement therapy. The study will compare the pharmacokinetics of oral versus intravenous T4 administration in organ donors, as well as, determine its ability to wean intropes in this patient population.

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Brain death criteria established

2. Consent for organ donation received

Exclusion Criteria:

1. immediate (< 4 Hrs) organ retrieval anticipated

Michael D Sharpe, MD FRCPC, Phone: 519-663-3030, Email: michael.sharpe@lhsc.on.ca

London Health Sciences Centre-UC, London, Ontario N6A5A5, Canada; Recruiting
Michael D Sharpe, Phone: 519-663-3030, Email: michael.sharpe@lhsc.on.ca

Related publications:

Novitzky D, Cooper DK, Chaffin JS, Greer AE, DeBault LE, Zuhdi N. Improved cardiac allograft function following triiodothyronine therapy to both donor and recipient. Transplantation. 1990 Feb;49(2):311-6.

Starting date: December 2004
Last updated: December 14, 2005