Reproductive Capacity and Iron Burden in Thalassemia (Fertility thal)

UCSF Benioff Children's Hospital Oakland

Status: Completed

Conditions: THALASSEMIA MAJOR

Treatments: Other: Blood Draw/Semen Exam; Other: Pituitary MRI; Other: Retrospective data/Chart Review/Relevant Clinical Results

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02308904

CICL670AUS46T

Details and patient eligibility

About

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.

Enrollment: 59 patients

Sex: All

Ages: 12+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Transfusion-dependent* females and males with thalassemia (any genotype) who are 12 to 45 years of age.
• History of at least 5 years of chronic transfusion (defined as ≥ 8 transfusions/year) (Age of initiation of transfusions does not matter)
• Any pubertal stage.
• Liver iron evaluated by SQUID, MRI or liver biopsy within 12 months prior to enrollment in the study.
• Need to be able to stop hormonal therapy for 3 weeks (males) and one month (females) prior to study enrollment.

Exclusion criteria

• Pregnant or lactating during study enrollment
• Unable to obtain liver iron concentration within 12 months prior or 6 months after study entry.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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59 participants in 3 patient groups

Laboratory Studies for Pituitary-Gonadal Function

Other group

Description:

Females: We expect to enroll approximately 15 females ages 12 years and older. Males: We expect to enroll approximately 15 males ages 12 years and older.

Treatment:

Other: Blood Draw/Semen Exam

Data on iron burden and chelation history

Other group

Description:

Retrospective data, as listed in this section, will be obtained from chart review and results of relevant clinical data. 1. Iron burden data 2. Assay for non-transferrin bound iron (NTBI) 3. Chelation data 4. Oxidant stress 5. History or presence of hypogonadism

Treatment:

Other: Retrospective data/Chart Review/Relevant Clinical Results

Pituitary MRI

Other group

Description:

MRI has been shown to demonstrate well the changes related to iron toxicity in the pituitary gland.

Treatment:

Other: Pituitary MRI