NCT02308904

Reproductive Capacity and Iron Burden in Thalassemia

Reproductive Capacity and Association to Iron Burden and Chelation Patterns in Thalassemia Major Patients

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 59 (actual)
• Sponsor: UCSF Benioff Children's Hospital Oakland · Academic / Other
• Sex: All
• Age: 12 Years
• Healthy volunteers: Accepted

Summary

The improved long-term survival of thalassemia major (TM) patients has resulted in increased focus on the ability to preserve fertility. While the association of iron toxicity with vital organ dysfunction, heart and liver, has been extensively investigated, the correlation of reproductive capacity and extent of iron overload is not well understood. Despite remarkable progress in methodology for prediction of reproductive status and intervention for preserving fertility, implementation in thalassemia is lacking. The investigators hypothesize that iron toxicity to the anterior pituitary occurring in the process of transfusional iron loading is directly associated with a decline in gonadal function. The investigators expect pituitary MRI measurements of iron deposition as well as markers of oxidative damage to correlate with the functional studies of pituitary-gonadal axis performed in this study. This cross sectional study will examine the relation of pituitary iron deposition and pituitary volume; serum iron and oxidative stress measures, liver iron concentration (LIC), cardiac iron and chelation adequacy with pituitary and gonadal reproductive hormone levels (and spermatogenesis in adult male patients), in order to better define the association of iron burden and chelation patterns with fertility potential, in thalassemia patients with iron overload. The study will assess whether the current chelation treatment regimens, in particular during the pubertal developmental age, are adequate for preserving fertility and could lead to improved chelation routines for preventing the high prevalence of compromised fertility. In addition, by utilizing state-of-the-art markers for fertility status, findings from this study may improve current methods for screening for hypogonadism and reproductive potential and allow earlier intervention. The investigators propose to examine 26-30 patients, 12 years and older, with measures of fertility potential, and correlate them to their current iron burden parameters and to the cumulative iron effect as indicated by past iron overload patterns and chelation history.

Conditions

• THALASSEMIA MAJOR

Interventions

Type	Name	Description
OTHER	Blood Draw/Semen Exam	Females: 1\. Obtain levels of LH/FSH, Estradiol, and AMH in all enrolled women. Males: We expect to enroll approximately 15 males ages 12 years and older. 1. Levels of FSH/LH and testosterone will be obtained. In addition, we will examine the association of the hormone inhibin B with mean fertility measures. Inhibin B levels were shown to correlate with azospermia and could demonstrate better prediction of reproductive potential. 2. Semen exam for determination of volume, sperm count, motility and sperm DNA integrity will be determined for interested adult thalassemia males (age ≥18 years and older).
OTHER	Retrospective data/Chart Review/Relevant Clinical Results	1. 1\. Documentation of liver iron from SQUID or MRI. 2. Transfusion data on age at onset of regular transfusions, transfusion frequency over the previous five years, and years of chronic transfusion therapy (defined as 8 or more per year). 3. Data on cardiac iron as indicated by T2\* MRI. 4. Ferritin levels. 2. NTBI will be accessed using a mobilizer ligand to collect NTBI from all pools as Fe-NTA which is then measured by HPLC. 3. 1\. Age at onset of chelation 2. Estimated periods of known or recalled non-compliance with regular chelation. 3. Listing of all chelation drugs previously used including dose and time period. 4. 1\. Vitamins E and C, at time closest to obtaining reproductive hormone levels. 2. Measuring the ratio of reduced gluthatione (GSH) to oxidized gluthatione (GSSG). 5. Assessment of time for pubertal development, assessment of menstrual history and need for treatment with gonadal hormone replacement.
OTHER	Pituitary MRI	MRI has been shown to demonstrate well the changes related to iron toxicity in the pituitary gland. An MRI protocol was optimized at Children's Hospital and Research Center Oakland (CHRCO) and Texas Children's Hospital. Utilizing 1.5 T clinical scanner to evaluate the iron accumulation in the anterior pituitary. The total data acquisition time is approximately 32 minutes. No sedation will be given. MRI data will be sent to Dr. Wang, department of Radiology, Children's Medical Center, University of Texas Southwestern Medical Center, Dallas, Texas. Quantification of R2, pituitary height and volume will be conducted.

Timeline

• Start date: 2013-06-01
• Primary completion: 2020-09-01
• Completion: 2020-09-01
• First posted: 2014-12-04
• Last updated: 2020-12-23

Locations

1 site across 1 country: United States